1 00:00:04,907 --> 00:00:08,823 GREETINGS. 2 00:00:08,823 --> 00:00:11,893 I'M WIN ARIAS AT THE NATIONAL 3 00:00:11,893 --> 00:00:14,095 INSTITUTES OF HEALTH IN 4 00:00:14,095 --> 00:00:15,463 BETHESDA, MARYLAND. 5 00:00:15,463 --> 00:00:18,933 IT CERTAINLY IS AN EXCITING 6 00:00:18,933 --> 00:00:20,668 PLEASURE TO HAVE ANOTHER SESSION 7 00:00:20,668 --> 00:00:24,372 IN OUR UNIQUE COURSE CALLED 8 00:00:24,372 --> 00:00:27,542 DEMYSTIFYING MEDICINE. 9 00:00:27,542 --> 00:00:29,277 LET ME EXPLAIN. 10 00:00:29,277 --> 00:00:31,179 THIS COURSE HAS BEEN IN 11 00:00:31,179 --> 00:00:33,514 EXISTENCE NOW FOR 22 YEARS AND 12 00:00:33,514 --> 00:00:35,583 IT'S INTENT -- IT'S REALLY A 13 00:00:35,583 --> 00:00:38,720 COURSE IN BRIDGE BUILDING. 14 00:00:38,720 --> 00:00:41,155 IT'S INTENT IS TO BRIDGE THE 15 00:00:41,155 --> 00:00:44,425 EXCITING DEVELOPMENTS IN 16 00:00:44,425 --> 00:00:44,959 BIOLOGY, ENGINEERING AND 17 00:00:44,959 --> 00:00:47,895 COMPUTER SCIENCE WITH MEDICINE. 18 00:00:47,895 --> 00:00:52,567 THE GOAL IS TO EXCITE OUR 19 00:00:52,567 --> 00:00:53,201 HETEROGENEOUS AUDIENCE, WHICH IS 20 00:00:53,201 --> 00:00:55,937 GLOBAL. 21 00:00:55,937 --> 00:00:59,474 THE LOGO IN THE UPPER RIGHT ON 22 00:00:59,474 --> 00:01:01,476 THE SLIDE IS THE CLASSIC 23 00:01:01,476 --> 00:01:05,546 BROOKLYN BRIDGE. 24 00:01:05,546 --> 00:01:08,116 AND LIKE ALWAYS IT REPRESENTS 25 00:01:08,116 --> 00:01:14,188 TWO INDIVIDUALS ON A CATWALK 26 00:01:14,188 --> 00:01:16,824 SHARING THEIR INFORMATION AND 27 00:01:16,824 --> 00:01:17,091 KNOWLEDGE. 28 00:01:17,091 --> 00:01:20,728 IN EFFECT, CONVERTING SILOS AS 29 00:01:20,728 --> 00:01:23,998 SHOWN IN THE BOTTOM RIGHT OF 30 00:01:23,998 --> 00:01:26,901 DETAILED INFORMATION AND OUT OF 31 00:01:26,901 --> 00:01:29,537 IT GENERATING NEW CONCEPTS, NEW 32 00:01:29,537 --> 00:01:32,673 IDEAS AND NEW PATHWAYS FOR THE 33 00:01:32,673 --> 00:01:37,512 ADVANCEMENT OF HUMAN HEALTH. 34 00:01:37,512 --> 00:01:40,248 SO THE COURSE MEETS ON TUESDAY 35 00:01:40,248 --> 00:01:41,949 AFTERNOONS FROM 3:00 TO 5:00 36 00:01:41,949 --> 00:01:42,650 FROM JANUARY UNTIL THE END OF 37 00:01:42,650 --> 00:01:46,988 MAY. 38 00:01:46,988 --> 00:01:50,258 YOU CAN WATCH IT ON THE 39 00:01:50,258 --> 00:01:50,858 VIDEOCAST LINK SHOWN ON THE 40 00:01:50,858 --> 00:01:55,396 SLIDE. 41 00:01:55,396 --> 00:01:58,499 WE ARE NOT GIVING CME CREDITS 42 00:01:58,499 --> 00:02:03,337 TODAY FOR REASONS I DON'T FULLY 43 00:02:03,337 --> 00:02:04,672 UNDERSTAND, BUT YOU ARE 44 00:02:04,672 --> 00:02:08,042 ENCOURAGED, PLEASE, TO SUBMIT 45 00:02:08,042 --> 00:02:08,576 QUESTIONS DURING THE 46 00:02:08,576 --> 00:02:11,913 PRESENTATIONS AND YOU DO THAT BY 47 00:02:11,913 --> 00:02:14,515 CLICKING THE SEND LIVE FEEDBACK 48 00:02:14,515 --> 00:02:17,351 ON THE VIDEOCAST DISPLAY ON YOUR 49 00:02:17,351 --> 00:02:21,355 COMPUTER. 50 00:02:21,355 --> 00:02:23,758 AND THESE QUESTIONS WILL THEN BE 51 00:02:23,758 --> 00:02:27,295 THE BASIS FOR WHAT IS ALWAYS A 52 00:02:27,295 --> 00:02:30,264 LIVELY Q&A AND DISCUSSION THAT 53 00:02:30,264 --> 00:02:36,637 FOLLOWS BOTH PRESENTATIONS. 54 00:02:36,637 --> 00:02:38,172 I BRING YOUR ATTENTION THAT ALL 55 00:02:38,172 --> 00:02:41,442 PREVIOUS SESSION FOR 22 YEARS 56 00:02:41,442 --> 00:02:52,119 ARE ARCHIVED IN THE NIH VIVID -- 57 00:02:52,119 --> 00:02:52,987 VIDEOCAST NETWORK. 58 00:02:52,987 --> 00:02:55,089 THE LINK ON THE SLIDE. 59 00:02:55,089 --> 00:02:56,657 IF YOU HAVE DESIRE FOR FURTHER 60 00:02:56,657 --> 00:03:00,795 INFORMATION CONTACT US AT 61 00:03:00,795 --> 00:03:08,503 DEMYSTIFYING MEDICINE@NIH.gov. 62 00:03:08,503 --> 00:03:10,605 TODAY'S SUBJECT IS PRIMARY 63 00:03:10,605 --> 00:03:14,809 CANCER OF THE COLON. 64 00:03:14,809 --> 00:03:18,045 WHICH HAS ATTRACTED AN 65 00:03:18,045 --> 00:03:23,618 INCREASING DEGREE OF ATTENTION 66 00:03:23,618 --> 00:03:26,454 BECAUSE OF ITS SEVERITY, 67 00:03:26,454 --> 00:03:29,924 FREQUENCY, AND ADVANCES MADE AND 68 00:03:29,924 --> 00:03:30,992 BEGINNING TO UNDERSTAND 69 00:03:30,992 --> 00:03:33,995 SOMETHING ABOUT THE BASIS OF 70 00:03:33,995 --> 00:03:35,663 THIS DISEASE, WHICH IS OFTEN 71 00:03:35,663 --> 00:03:39,267 FATAL. 72 00:03:39,267 --> 00:03:40,635 IN FACT USUALLY. 73 00:03:40,635 --> 00:03:43,104 SO SOME OF THE QUESTIONS THAT 74 00:03:43,104 --> 00:03:45,106 POPPED INTO MY MIND ARE 75 00:03:45,106 --> 00:03:45,873 INDICATED ON THE SLIDE. 76 00:03:45,873 --> 00:03:50,177 AND THEY REALLY SERVE AS 77 00:03:50,177 --> 00:03:52,713 INTRODUCTION TO OUR TWO 78 00:03:52,713 --> 00:03:55,449 OUTSTANDING INDIVIDUALS WHO HAVE 79 00:03:55,449 --> 00:03:58,185 BEEN KIND ENOUGH TO MAKE 80 00:03:58,185 --> 00:04:00,454 PRESENTATIONS. 81 00:04:00,454 --> 00:04:03,624 SO THE FIRST IS, IS THE 82 00:04:03,624 --> 00:04:08,362 INCIDENCE OF COLON CANCER 83 00:04:08,362 --> 00:04:08,663 INCREASING? 84 00:04:08,663 --> 00:04:12,233 IF SO, IS IT WORLDWIDE? 85 00:04:12,233 --> 00:04:14,802 IS IT IN ANY PARTICULAR GROUP OF 86 00:04:14,802 --> 00:04:15,736 INDIVIDUALS THAT MAY GIVE SOME 87 00:04:15,736 --> 00:04:21,742 INCLUDE AS TO WHAT IS GOING ON 88 00:04:21,742 --> 00:04:22,109 MECHANISTICALLY? 89 00:04:22,109 --> 00:04:23,878 AND ARE THERE EPIDEMIOLOGIC 90 00:04:23,878 --> 00:04:26,213 CLUES AS TO WHAT COULD BE RISK 91 00:04:26,213 --> 00:04:27,915 FACTORS OR PERHAPS EVEN FACTORS 92 00:04:27,915 --> 00:04:32,587 THAT ARE PROTECTIVE? 93 00:04:32,587 --> 00:04:35,923 NOW, EVERYBODY KNOWS ABOUT 94 00:04:35,923 --> 00:04:38,960 COLONOSCOPY AND TESTING OF BLOOD 95 00:04:38,960 --> 00:04:44,932 IN THE STOOL, ALL DIRECTED TO 96 00:04:44,932 --> 00:04:46,300 EARLY DIAGNOSIS AND IMPROVED 97 00:04:46,300 --> 00:04:48,135 TREATMENT BUT HOW EFFECTIVE ARE 98 00:04:48,135 --> 00:04:52,740 THESE PROCEDURES? 99 00:04:52,740 --> 00:04:53,874 MOST IMPORTANTLY, WHAT PUBLIC 100 00:04:53,874 --> 00:04:56,577 HEALTH GUIDANCE IS CRITICAL? 101 00:04:56,577 --> 00:05:00,114 THIS IS THE BASIC SUBJECT AREA 102 00:05:00,114 --> 00:05:06,120 IN WHICH OUR FIRST SPEAKER, 103 00:05:06,120 --> 00:05:10,224 REBECCA SIEGEL WILL ADDRESS. 104 00:05:10,224 --> 00:05:12,126 THEN THERE'S A GENETIC 105 00:05:12,126 --> 00:05:14,562 RELATIONSHIP TO THE VARIOUS 106 00:05:14,562 --> 00:05:17,898 INHERITABLE CANCER SYNDROME. 107 00:05:17,898 --> 00:05:20,034 IS THE MICROBIOME A CRITICAL 108 00:05:20,034 --> 00:05:20,267 FACTOR? 109 00:05:20,267 --> 00:05:26,007 AFTER ALL, THIS IS THE COLON THE 110 00:05:26,007 --> 00:05:27,475 MAJOR SITE OF THE MICROBIOME. 111 00:05:27,475 --> 00:05:30,811 AND HOW HAVE ADVANCES IN 112 00:05:30,811 --> 00:05:32,613 MOLECULAR BIOLOGY AND GENETICS, 113 00:05:32,613 --> 00:05:35,816 HAVE THEY PROVIDED BETTER 114 00:05:35,816 --> 00:05:37,051 DIAGNOSIS AND TREATMENT? 115 00:05:37,051 --> 00:05:39,553 OF COURSE THE HUGE QUESTION IS 116 00:05:39,553 --> 00:05:43,824 WHAT ARE THE BIG CHALLENGES FOR 117 00:05:43,824 --> 00:05:47,561 BETTER PREVENTION, DETECTION AND 118 00:05:47,561 --> 00:05:48,129 TREATMENT? 119 00:05:48,129 --> 00:05:51,465 AND THIS LATTER PORTION OF MY 120 00:05:51,465 --> 00:05:56,237 QUESTION WAS WHAT WE ADDRESSED 121 00:05:56,237 --> 00:05:57,371 BY SANDY, WHOM I'LL INTRODUCE IN 122 00:05:57,371 --> 00:06:01,542 A MOMENT. 123 00:06:01,542 --> 00:06:11,485 SO, OUR FIRST SPEAKER IS REBECCA 124 00:06:11,485 --> 00:06:12,920 SIEGEL WHO TOOK HER DEGREE IN 125 00:06:12,920 --> 00:06:13,988 GENETICS AT THE UNIVERSITY OF 126 00:06:13,988 --> 00:06:16,724 GEORGIA AND FOLLOWED BY A MASTER 127 00:06:16,724 --> 00:06:19,060 IN PUBLIC HEALTH IN EMORY IN THE 128 00:06:19,060 --> 00:06:22,063 SCHOOL OF PUBLIC HEALTH. 129 00:06:22,063 --> 00:06:26,200 REBECCA IS THE SENIOR SCIENTIFIC 130 00:06:26,200 --> 00:06:27,301 DIRECTOR OF SURVEILLANCE 131 00:06:27,301 --> 00:06:27,935 RESEARCH AT THE AMERICAN CANCER 132 00:06:27,935 --> 00:06:36,610 SOCIETY. 133 00:06:36,610 --> 00:06:42,883 SHE IS A LEADING EPIDEMIOLOGIST 134 00:06:42,883 --> 00:06:44,018 AND EPIDEMIOLOGY IS THE FIRST 135 00:06:44,018 --> 00:06:47,488 STEP IN MEDICINE BEFORE ADVANCES 136 00:06:47,488 --> 00:06:51,926 IN PUBLIC HEALTH TAKE PLACE. 137 00:06:51,926 --> 00:06:54,328 THE RESEARCH FOCUS OF HER WORK 138 00:06:54,328 --> 00:06:56,464 ARE DISPARITIES AND COLON RECTAL 139 00:06:56,464 --> 00:07:00,267 CANCER. 140 00:07:00,267 --> 00:07:02,536 WHO GETS IT? 141 00:07:02,536 --> 00:07:03,137 PARTICULARLY WITH RESPECT TO 142 00:07:03,137 --> 00:07:08,142 AGE. 143 00:07:08,142 --> 00:07:10,010 AND HER EPIDEMIOLOGIC STUDIES 144 00:07:10,010 --> 00:07:14,215 HAVE HAD A BIG EFFECT ON MENTAL 145 00:07:14,215 --> 00:07:17,284 HEALTH POLICY. 146 00:07:17,284 --> 00:07:18,252 THEY'VE CHANGED THE AMERICAN 147 00:07:18,252 --> 00:07:20,154 CANCER SOCIETY FOR SCREENING 148 00:07:20,154 --> 00:07:20,454 GUIDELINES. 149 00:07:20,454 --> 00:07:23,457 WE'LL HEAR MORE ABOUT THIS. 150 00:07:23,457 --> 00:07:29,797 OUR SECOND SPEAKER IS SANFORD 151 00:07:29,797 --> 00:07:31,332 MARKOWITZ WHO TOOK HIS DEGREE IN 152 00:07:31,332 --> 00:07:35,236 CHEMISTRY AND PHYSIC INS HARVARD 153 00:07:35,236 --> 00:07:39,406 AND THEN M.D. AND Ph.D. AT YALE. 154 00:07:39,406 --> 00:07:41,242 SANDY IS A PROFESSOR OF MANY 155 00:07:41,242 --> 00:07:42,409 THINGS. 156 00:07:42,409 --> 00:07:46,213 HE'S A PROFESSOR OF CANCER 157 00:07:46,213 --> 00:07:49,784 GENETICS, OF GENETICS AND 158 00:07:49,784 --> 00:07:53,354 GENOMIC SCIENCES, AND MOLECULAR 159 00:07:53,354 --> 00:07:55,556 AND MICROBIOLOGY AND CO-LEADER 160 00:07:55,556 --> 00:07:56,657 OF THE G.I. GENETICS PROGRAM 161 00:07:56,657 --> 00:08:00,261 PART OF THE COMPREHENSIVE CANCER 162 00:08:00,261 --> 00:08:00,961 CENTER. 163 00:08:00,961 --> 00:08:03,364 ALL OF THIS AT CASE WESTERN 164 00:08:03,364 --> 00:08:03,964 RESERVE UNIVERSITY SCHOOL OF 165 00:08:03,964 --> 00:08:09,436 MEDICINE. 166 00:08:09,436 --> 00:08:12,873 NOW, THIS WORK HAS BEEN 167 00:08:12,873 --> 00:08:15,609 OUTSTANDING AND HIS WORK IS 168 00:08:15,609 --> 00:08:18,212 DIRECTED TOWARDS IDENTIFYING 169 00:08:18,212 --> 00:08:21,382 MOLECULAR ABNORMALITIES IN BOTH 170 00:08:21,382 --> 00:08:23,584 THE SPORADIC TYPE OF COLORECTAL 171 00:08:23,584 --> 00:08:29,857 CANCER AND ALSO IN THE NUMEROUS 172 00:08:29,857 --> 00:08:30,324 INHERITABLE SYNDROMES. 173 00:08:30,324 --> 00:08:34,061 HIS WORK IS DIRECTED TO 174 00:08:34,061 --> 00:08:38,199 IDENTIFYING BOTH POSITIVE AND 175 00:08:38,199 --> 00:08:40,668 NEGATIVE REGULATORY GROWTH 176 00:08:40,668 --> 00:08:43,370 FACTORS AND MORE RECENTLY THE 177 00:08:43,370 --> 00:08:46,207 ROLE OF GENOMIC INSTABILITY. 178 00:08:46,207 --> 00:08:50,144 AND ALL OF THIS HAS HAD A 179 00:08:50,144 --> 00:08:53,080 PROFOUND INFLUENCE ON BETTER 180 00:08:53,080 --> 00:08:54,415 UNDERSTANDING IN OUR CURRENT 181 00:08:54,415 --> 00:08:57,885 STATUS OF POSSIBLE UNDERLYING 182 00:08:57,885 --> 00:09:00,254 MECHANISMS RESPONSIBLE FOR THE 183 00:09:00,254 --> 00:09:02,523 COLORECTAL PROBLEM. 184 00:09:02,523 --> 00:09:06,861 SO, WE WILL BEGIN WITH OUR FIRST 185 00:09:06,861 --> 00:09:09,430 SPEAKER, REBECCA SIEGEL, WILL 186 00:09:09,430 --> 00:09:12,800 YOU PLEASE CARRY ON. 187 00:09:12,800 --> 00:09:16,003 >> THANK YOU SO MUCH, DR. ARIAS. 188 00:09:16,003 --> 00:09:19,573 I AM THRILLED TO BE HERE AND I'M 189 00:09:19,573 --> 00:09:30,117 GOING TO SHARE MY SCREEN -- CAN 190 00:09:34,255 --> 00:09:40,661 YOU SEE THE SLIDES? 191 00:09:40,661 --> 00:09:41,195 OKAY. 192 00:09:41,195 --> 00:09:42,196 ALL RIGHT. 193 00:09:42,196 --> 00:09:44,365 SO THANK YOU SO MUCH FOR THE 194 00:09:44,365 --> 00:09:46,467 INTRODUCTION, DR. ARIAS. 195 00:09:46,467 --> 00:09:49,169 I'M THRILLED TO BE HERE TODAY TO 196 00:09:49,169 --> 00:09:51,238 TALK ABOUT THE CHANGING 197 00:09:51,238 --> 00:09:53,007 LANDSCAPE OF COLORECTAL CANCER 198 00:09:53,007 --> 00:09:55,542 AND HOW THE DISEASE IS BECOMING 199 00:09:55,542 --> 00:09:57,811 MUCH MORE COMMON IN YOUNGER 200 00:09:57,811 --> 00:09:58,045 ADULTS. 201 00:09:58,045 --> 00:10:00,214 SO REALLY BECOMING MORE OF A 202 00:10:00,214 --> 00:10:04,952 HORSE THAN A ZEBRA IN THE EXAM 203 00:10:04,952 --> 00:10:06,186 ROOM. 204 00:10:06,186 --> 00:10:10,257 OUR OBJECTIVES ARE TO LEARN 205 00:10:10,257 --> 00:10:17,064 ABOUT HOW THESE CHANGES IN 206 00:10:17,064 --> 00:10:19,166 COLORECTAL CANCER ARE THE RESULT 207 00:10:19,166 --> 00:10:20,968 OF A STRONG BIRTH COHORT EFFECT 208 00:10:20,968 --> 00:10:21,735 AND SHIFT OUTSIDE THE 209 00:10:21,735 --> 00:10:23,337 U.S. BORDERS AND LOOK AT WHETHER 210 00:10:23,337 --> 00:10:27,474 THIS IS HAPPENING GLOBALLY AS 211 00:10:27,474 --> 00:10:27,675 WELL. 212 00:10:27,675 --> 00:10:31,545 AND THEN WE WILL LOOK AT SOME 213 00:10:31,545 --> 00:10:32,813 POTENTIAL CAUSES AT A VERY HIGH 214 00:10:32,813 --> 00:10:34,648 LEVEL AND OPPORTUNITIES FOR 215 00:10:34,648 --> 00:10:36,183 MITIGATING THE BURDEN WHILE 216 00:10:36,183 --> 00:10:38,986 WE'RE STILL WAITING ON ANSWERS 217 00:10:38,986 --> 00:10:44,925 FOR THOSE SPECIFIC CAUSES. 218 00:10:44,925 --> 00:10:46,560 THE INFORMATION IN THIS FIRST 219 00:10:46,560 --> 00:10:52,032 SECTION IS BASED ON HIGH-QUALITY 220 00:10:52,032 --> 00:10:52,766 POPULATION-BASED CANCER REGISTRY 221 00:10:52,766 --> 00:11:00,741 DATA EITHER FROM NCI, SEER 222 00:11:00,741 --> 00:11:02,910 PROGRAM OR DATA FROM THE 223 00:11:02,910 --> 00:11:04,745 NATIONAL CANCER PROGRAM OF 224 00:11:04,745 --> 00:11:07,314 CANCER REGISTRIES AT CDC. 225 00:11:07,314 --> 00:11:11,719 WE RECEIVED THIS COMBINEDED DATA 226 00:11:11,719 --> 00:11:12,886 SET FROM THE NORTHERN AMERICAN 227 00:11:12,886 --> 00:11:14,421 REGISTRY OF CENTRAL REGISTRIES. 228 00:11:14,421 --> 00:11:17,291 WHICH IS A STANDARD CENTER THAT 229 00:11:17,291 --> 00:11:19,693 ENSURES HIGH QUALITY DATA AT AN 230 00:11:19,693 --> 00:11:20,361 UMBRELLA ORGANIZATION THAT IS 231 00:11:20,361 --> 00:11:22,196 ALSO A CONVENER. 232 00:11:22,196 --> 00:11:23,864 SO ALL OF THESE ORGANIZATIONS 233 00:11:23,864 --> 00:11:24,531 ARE VERY IMPORTANT IN THE WORK 234 00:11:24,531 --> 00:11:31,271 THAT WE DO. 235 00:11:31,271 --> 00:11:32,506 MORTALITY IS A LITTLE MORE 236 00:11:32,506 --> 00:11:32,873 STRAIGHTFORWARD. 237 00:11:32,873 --> 00:11:35,376 IT'S PROVIDED BY THE NATIONAL 238 00:11:35,376 --> 00:11:37,378 CENTER FOR HEALTH STATISTICS AND 239 00:11:37,378 --> 00:11:39,413 ALSO AT CDC BASED ON THE 240 00:11:39,413 --> 00:11:40,447 UNDERLYING CAUSE OF DEATH 241 00:11:40,447 --> 00:11:43,150 RECORDED ON DEATH CERTIFICATES. 242 00:11:43,150 --> 00:11:45,519 FOR ALL 50 STATES AND D.C. AND 243 00:11:45,519 --> 00:11:48,322 OF COURSE WE HAVE THIS DATA 244 00:11:48,322 --> 00:11:52,726 GOING BACK TO BEFORE THE 1930s. 245 00:11:52,726 --> 00:12:02,202 IN ADDITION TO INCIDENTS OF 246 00:12:02,202 --> 00:12:03,270 MORTALITY AND BECAUSE OF THE 247 00:12:03,270 --> 00:12:05,005 TIME REQUIRED TO COLLECT THE 248 00:12:05,005 --> 00:12:08,142 DATA AND DISSEMINATE IT, THE 249 00:12:08,142 --> 00:12:09,743 AMERICAN CANCER SOCIETY ANNUALLY 250 00:12:09,743 --> 00:12:12,112 PRODUCES ESTIMATED CASES IN 251 00:12:12,112 --> 00:12:14,214 DEATHS FOR THE CURRENT YEAR AND 252 00:12:14,214 --> 00:12:16,650 WE DO THIS IN COLLABORATION WITH 253 00:12:16,650 --> 00:12:18,085 STATISTICIANS AT NCI. 254 00:12:18,085 --> 00:12:20,587 SO I DO HAVE ONE SLIDE THAT 255 00:12:20,587 --> 00:12:22,222 INCLUDES OUR ESTIMATES. 256 00:12:22,222 --> 00:12:26,560 THEN WE ALSO USE NCI SOFTWARE TO 257 00:12:26,560 --> 00:12:27,161 CALCULATE RATES AND QUANTIFY 258 00:12:27,161 --> 00:12:31,832 TRENDS. 259 00:12:31,832 --> 00:12:34,735 SO THIS SLIDE SHOWS LONG-TERM 260 00:12:34,735 --> 00:12:37,638 TRENDS IN OVER ALL COLORECTAL 261 00:12:37,638 --> 00:12:40,174 CANCER INCIDENTS AND MORTALITY. 262 00:12:40,174 --> 00:12:41,875 AND COLORECTAL CANCER IS ONE OF 263 00:12:41,875 --> 00:12:43,677 THE CANCERS THAT IS OFTEN TOUTED 264 00:12:43,677 --> 00:12:46,713 AS A SUCCESS STORY ESPECIALLY IN 265 00:12:46,713 --> 00:12:48,916 THE U.S. BECAUSE INCIDENTS AND 266 00:12:48,916 --> 00:12:50,984 DEATH RATES HAVE BEEN DECLINING 267 00:12:50,984 --> 00:12:52,653 FOR DECADES. 268 00:12:52,653 --> 00:12:55,122 THIS IS BECAUSE OF CHANGING 269 00:12:55,122 --> 00:12:58,525 PATTERNS IN RISK FACTORS LIKE 270 00:12:58,525 --> 00:13:02,029 REDUCTIONS IN SMOKING, SMOKING 271 00:13:02,029 --> 00:13:03,330 INCREASES RISK AS WELL AS 272 00:13:03,330 --> 00:13:06,800 INCREASED USE OF 273 00:13:06,800 --> 00:13:08,001 ANTI-INFLAMMATORY DRUGS WHICH 274 00:13:08,001 --> 00:13:09,470 DECREASE RISK. 275 00:13:09,470 --> 00:13:11,538 AND THEN DURING THE 2000s THERE 276 00:13:11,538 --> 00:13:16,877 WAS THE WIDESPREAD UPTAKE OF 277 00:13:16,877 --> 00:13:19,146 COLONOSCOPY SCREENING AND 278 00:13:19,146 --> 00:13:20,214 COLONOSCOPY, AS I'M SURE YOU 279 00:13:20,214 --> 00:13:24,118 KNOW, DETECTS CANCER EARLY BUT 280 00:13:24,118 --> 00:13:29,723 ACTUALLY THE PRIMARY WAY THAT 281 00:13:29,723 --> 00:13:33,427 COLORECT OL CANCER SCREENING 282 00:13:33,427 --> 00:13:36,196 WORKS IS TO PREVENT CANCER. 283 00:13:36,196 --> 00:13:42,202 IT CAUSED A LARGE ACCELERATION 284 00:13:42,202 --> 00:13:44,738 FOR INCIDENTS AND MORTALITY. 285 00:13:44,738 --> 00:13:47,808 IN THE PAST DECADE THERE'S BEEN 286 00:13:47,808 --> 00:13:50,410 DECLINES IN INCIDENTS OF ABOUT 287 00:13:50,410 --> 00:13:52,880 1% A YEAR AND A LITTLE STEEPER 288 00:13:52,880 --> 00:13:55,315 DECLINES IN MORTALITY BECAUSE OF 289 00:13:55,315 --> 00:13:56,083 THE ADDITIONAL CONTRIBUTION OF 290 00:13:56,083 --> 00:14:04,057 ADVANCES IN TREATMENT. 291 00:14:04,057 --> 00:14:08,695 HOWEVER AS WE KNOW FROM -- I 292 00:14:08,695 --> 00:14:09,129 WOU 293 00:14:09,129 --> 00:14:16,570 WOULD ARGUE TO SAY FROM OUR MOST 294 00:14:16,570 --> 00:14:17,137 FAMOUS EPIDEMIOLOGIST THAT 295 00:14:17,137 --> 00:14:18,071 PROGRESS MUST BE EVALUATED WITH 296 00:14:18,071 --> 00:14:20,207 RESPECT TO YOUNGER ADULTS 297 00:14:20,207 --> 00:14:20,908 BECAUSE CANCER OCCURRING IN 298 00:14:20,908 --> 00:14:28,549 YOUNG ADULT IS THE FIRST TO WILL 299 00:14:28,549 --> 00:14:29,850 BEAR INFLUENCE OF CARCINOGENIC 300 00:14:29,850 --> 00:14:30,217 EXPOSURES. 301 00:14:30,217 --> 00:14:32,619 WHEN WE BREAK OUT THE TRENDS AND 302 00:14:32,619 --> 00:14:36,123 INCIDENTS BY AGE, IT BECOMES 303 00:14:36,123 --> 00:14:39,226 IMMEDIATELY CLEAR THAT THE OVER 304 00:14:39,226 --> 00:14:41,295 ALL PROGRESS IS MASKING 305 00:14:41,295 --> 00:14:44,364 INCREASING INCIDENTS IN YOUNG 306 00:14:44,364 --> 00:14:45,832 ADULTS. 307 00:14:45,832 --> 00:14:47,401 INCIDENT RATES HAVE BEEN 308 00:14:47,401 --> 00:14:49,269 INCREASING STEEPLY IN PEOPLE 65 309 00:14:49,269 --> 00:14:52,339 AND OVER BY ABOUT 2.6% PER YEAR 310 00:14:52,339 --> 00:14:54,074 IN THE PAST DECADE. 311 00:14:54,074 --> 00:14:56,610 WHILE DURING THE SAME TIME 312 00:14:56,610 --> 00:14:58,612 PERIOD, THERE WERE INCREASES OF 313 00:14:58,612 --> 00:15:00,447 THE SAME MAGNITUDE IN PEOPLE 314 00:15:00,447 --> 00:15:04,518 UNDER 50. 315 00:15:04,518 --> 00:15:07,454 AND NOW EVEN IN PEOPLE AGE 50 TO 316 00:15:07,454 --> 00:15:09,223 64 WHICH I'LL REFER TO AS MIDDLE 317 00:15:09,223 --> 00:15:13,427 AGE, RATES ARE INCREASING BY 318 00:15:13,427 --> 00:15:14,695 0.4% PER YEAR. 319 00:15:14,695 --> 00:15:16,163 YOU MIGHT SAY THIS DOESN'T SEEM 320 00:15:16,163 --> 00:15:19,533 LIKE A VERY BIG INCREASE AND IT 321 00:15:19,533 --> 00:15:22,002 ISN'T EXCEPT THAT IT'S ON THE 322 00:15:22,002 --> 00:15:25,105 HEELS OF RAPID DECLINES IN THIS 323 00:15:25,105 --> 00:15:28,675 AGE GROUP THAT VERY MUCH MIRROR 324 00:15:28,675 --> 00:15:30,444 THE PATTERNS IN PEOPLE 65 AND 325 00:15:30,444 --> 00:15:30,711 OVER. 326 00:15:30,711 --> 00:15:33,580 SO WHY WOULD YOU HAVE THIS 327 00:15:33,580 --> 00:15:36,416 ABRUPT CHANGE? 328 00:15:36,416 --> 00:15:38,652 THE REASON IS BECAUSE OF A 329 00:15:38,652 --> 00:15:41,822 STRONGER BOTH COHERT EFFECT. 330 00:15:41,822 --> 00:15:46,226 PEOPLE BORN AFTER CIRCA 1950 331 00:15:46,226 --> 00:15:56,870 HAVE ELEVATED RISK OF KOL J JLO 332 00:15:56,870 --> 00:15:58,839 COLORECTAL CANCER AND INCREASES 333 00:15:58,839 --> 00:16:02,876 AND PEOPLE LIKE ME BORN IN THE 334 00:16:02,876 --> 00:16:07,281 1960s ARE ON THE CUSP OF HIGHER 335 00:16:07,281 --> 00:16:10,083 RISK AND I CARRY THE ELEVATED 336 00:16:10,083 --> 00:16:10,550 RISK WITH ME. 337 00:16:10,550 --> 00:16:11,852 THAT'S WHY THE RATES ARE TICKING 338 00:16:11,852 --> 00:16:13,453 UP NOW WHEN THEY WERE JUST 339 00:16:13,453 --> 00:16:21,595 DECLINING VERY RECENTLY. 340 00:16:21,595 --> 00:16:24,831 THESE NEXT TWO SLIDES ARE 341 00:16:24,831 --> 00:16:27,167 SHOWING FROM SLIDES FROM YEARS 342 00:16:27,167 --> 00:16:27,334 AGO. 343 00:16:27,334 --> 00:16:30,103 THEY DO A GOOD JOB AT 344 00:16:30,103 --> 00:16:31,705 ILLUSTRATING THE BIRTH COHORT 345 00:16:31,705 --> 00:16:35,142 WHICH CAN BE A DIFFICULT 346 00:16:35,142 --> 00:16:35,609 CONCEPT. 347 00:16:35,609 --> 00:16:40,013 SO THIS SLIDE SHOWS AND THESE 348 00:16:40,013 --> 00:16:42,616 ARE TRENDS FOR COLON CANCER ON 349 00:16:42,616 --> 00:16:47,721 THE TOP AND COLORECTAL ON THE 350 00:16:47,721 --> 00:16:54,094 BOTTOM BY 10 AGE GROUP 20 TO 54. 351 00:16:54,094 --> 00:16:57,197 THE DOTS ARE OBSERVED RATES AND 352 00:16:57,197 --> 00:16:58,899 THE LINES ARE THE JOINT POINT 353 00:16:58,899 --> 00:16:59,399 TREND. 354 00:16:59,399 --> 00:17:00,867 THE FOCUS SHOULD BE ON THE LINES 355 00:17:00,867 --> 00:17:02,202 AND WHETHER THEY'RE INCREASING 356 00:17:02,202 --> 00:17:12,446 OR DECREASING. 357 00:17:18,285 --> 00:17:21,455 IF PEOPLE IN THEIR 20s, INCIDENT 358 00:17:21,455 --> 00:17:23,890 RATES OF RECTAL CANCER HAVE BEEN 359 00:17:23,890 --> 00:17:25,025 INCREASING SINCE AT LEAST THE 360 00:17:25,025 --> 00:17:27,227 MID '70s. 361 00:17:27,227 --> 00:17:29,996 BUT RATES DIDN'T BEGIN 362 00:17:29,996 --> 00:17:32,199 INCREASING UNTIL 1980 IN PEOPLE 363 00:17:32,199 --> 00:17:33,867 IN THEIR 30s. 364 00:17:33,867 --> 00:17:36,603 1991, IN PEOPLE IN THEIR 40s AND 365 00:17:36,603 --> 00:17:38,872 SO ON. 366 00:17:38,872 --> 00:17:42,309 SO THIS UP TICK MOVES FORWARD IN 367 00:17:42,309 --> 00:17:44,711 TIME WITH INCREASING AGE LIKE A 368 00:17:44,711 --> 00:17:50,951 SLOW MOVING TSUNAMI. 369 00:17:50,951 --> 00:17:53,453 AND THIS IS FROM THE PAPER 370 00:17:53,453 --> 00:17:56,690 SHOWING AGE SPECIFIC INCIDENTS 371 00:17:56,690 --> 00:17:59,926 OF COLON CANCER IN BLUE AND 372 00:17:59,926 --> 00:18:04,264 RECTAL CANCER IN ORANGE AND 373 00:18:04,264 --> 00:18:07,367 GENERATIONS FROM PEOPLE BORN IN 374 00:18:07,367 --> 00:18:13,407 THE LATE 1800s UNTIL 1990. 375 00:18:13,407 --> 00:18:15,008 AND THIS IS RELATIVE RISK SO 376 00:18:15,008 --> 00:18:18,278 IT'S THE RISK OF THESE 377 00:18:18,278 --> 00:18:20,514 GENERATIONS COMPARED TO PEOPLE 378 00:18:20,514 --> 00:18:23,383 BORN IN 1949 WHO HAVE THE LOWEST 379 00:18:23,383 --> 00:18:25,352 RISK AND YOU CAN SEE THAT 380 00:18:25,352 --> 00:18:26,420 INDICATED BY THE DOTTED LINE 381 00:18:26,420 --> 00:18:28,088 HERE. 382 00:18:28,088 --> 00:18:31,858 IT LOOKS A LITTLE OFF CENTER SO 383 00:18:31,858 --> 00:18:34,694 THAT, THAT LOWEST RISK COHORT 384 00:18:34,694 --> 00:18:38,165 WAS BORN CIRCA 1949. 385 00:18:38,165 --> 00:18:39,633 OFTEN I SAY 1950 BECAUSE PEOPLE 386 00:18:39,633 --> 00:18:40,867 CAN REMEMBER THAT EASIER BUT 387 00:18:40,867 --> 00:18:44,237 THAT'S WHY THE DOTTED LINE LOOKS 388 00:18:44,237 --> 00:18:47,240 A LITTLE OFF THERE BECAUSE THE 389 00:18:47,240 --> 00:18:49,309 MEDIAN BIRTH YEAR FOR THE COHORT 390 00:18:49,309 --> 00:18:52,712 IS 1949. 391 00:18:52,712 --> 00:18:55,515 SO EVERY GENERATION SUBSEQUENT 392 00:18:55,515 --> 00:18:59,719 TO 1949 HAS A LITTLE BIT HIGHER 393 00:18:59,719 --> 00:19:02,055 RISK SO PEOPLE BORN IN 1990 HAVE 394 00:19:02,055 --> 00:19:04,124 TWICE THE RISK OF COLON CANCER 395 00:19:04,124 --> 00:19:07,060 AND FOUR TIMES THE RISK OF 396 00:19:07,060 --> 00:19:08,695 RECTAL CANCER COMPARED TO PEOPLE 397 00:19:08,695 --> 00:19:12,032 BORN IN 1949. 398 00:19:12,032 --> 00:19:14,000 ANOTHER THING THAT YOU CAN 399 00:19:14,000 --> 00:19:17,037 NOTICE HERE IN THE FIRST LINE I 400 00:19:17,037 --> 00:19:19,973 TALKED ABOUT CHANGING PATTERNS 401 00:19:19,973 --> 00:19:22,342 IN RISK FACTORS THAT REDUCED 402 00:19:22,342 --> 00:19:22,709 RISK. 403 00:19:22,709 --> 00:19:24,945 AND YOU CAN SEE THAT IN THE 404 00:19:24,945 --> 00:19:26,279 FIRST HALF OF THE FIGURE WHERE 405 00:19:26,279 --> 00:19:29,416 RISK WAS DECLINING UNTIL THE 406 00:19:29,416 --> 00:19:33,153 1949 BIRTH COHORT. 407 00:19:33,153 --> 00:19:34,521 SO WHAT DOES THIS MEAN? 408 00:19:34,521 --> 00:19:36,389 WELL, WHEN YOU HAVE A VERY 409 00:19:36,389 --> 00:19:38,959 STRONG BIRTH COHORT EFFECT LIKE 410 00:19:38,959 --> 00:19:42,963 THIS, IT TELLS YOU THAT THE 411 00:19:42,963 --> 00:19:47,400 CHANGING RISK IS BECAUSE OF 412 00:19:47,400 --> 00:19:47,701 EXPOSURES. 413 00:19:47,701 --> 00:19:50,437 AND THERE'S BEEN EITHER AN 414 00:19:50,437 --> 00:19:55,642 INTRODUCTION OF A NEW 415 00:19:55,642 --> 00:19:58,245 CARCINOGENIC EXPOSURE IN 1949 416 00:19:58,245 --> 00:19:59,646 WITH SUBSEQUENT GENERATIONS 417 00:19:59,646 --> 00:20:02,349 HAVING ACCUMULATIVE INCREASED 418 00:20:02,349 --> 00:20:04,918 RISK OR COULD BE A DECLINE IN 419 00:20:04,918 --> 00:20:07,854 THE PROTECTIVE FACTOR LIKE WE 420 00:20:07,854 --> 00:20:09,256 SAW WITH THE EARLIER SLIDE. 421 00:20:09,256 --> 00:20:12,659 SO REDUCTIONS IN SMOKE AND 422 00:20:12,659 --> 00:20:17,931 INCREASED USE OF 423 00:20:17,931 --> 00:20:18,899 ANTI-INFLAMMATORY DRUGS MAY HAVE 424 00:20:18,899 --> 00:20:20,100 DIFFERENT EFFECTS BUT BOTH WORK 425 00:20:20,100 --> 00:20:25,939 TO RECREASING RISK. 426 00:20:25,939 --> 00:20:28,008 HERE WE HAVE DECREASING HISPANIC 427 00:20:28,008 --> 00:20:29,643 BUT DON'T KNOW WHY. 428 00:20:29,643 --> 00:20:35,582 BACK TO OUR CONTEMPORARY DATA 429 00:20:35,582 --> 00:20:38,084 AND WE HAVE INCREASED RATES IN 430 00:20:38,084 --> 00:20:46,626 YOUNGER ADULTS THE MEDIAN AGE OF 431 00:20:46,626 --> 00:20:47,994 COLORECTAL CANCER HAS DROPPED IN 432 00:20:47,994 --> 00:20:49,563 JUST TWO DECADES. 433 00:20:49,563 --> 00:20:54,200 AND WE'RE ALSO SEEING THIS PLAY 434 00:20:54,200 --> 00:21:00,240 OUT THE SHIFT TO ANNUAL AGE 435 00:21:00,240 --> 00:21:01,641 DIAGNOSIS AND THESE ARE OUR 436 00:21:01,641 --> 00:21:04,744 ESTIMATED CASES FOR 2025. 437 00:21:04,744 --> 00:21:09,115 WE'RE EXPECTING A LITTLE OVER 438 00:21:09,115 --> 00:21:11,318 154,000 CASES OF COLORECTAL 439 00:21:11,318 --> 00:21:14,187 CANCER WILL BE DIAGNOSED IN THE 440 00:21:14,187 --> 00:21:14,354 U.S. 441 00:21:14,354 --> 00:21:17,424 OF THESE, 44% WILL BE DIAGNOSED 442 00:21:17,424 --> 00:21:20,126 IN PEOPLE IN THEIR EARLY 60s OR 443 00:21:20,126 --> 00:21:20,460 YOUNGER. 444 00:21:20,460 --> 00:21:26,199 THIS IS UP FROM 27% FROM 1995. 445 00:21:26,199 --> 00:21:29,202 ADDITIONALLY, 21,000 OF THESE 446 00:21:29,202 --> 00:21:33,440 NEW DIAGNOSES WILL BE PEOPLE IN 447 00:21:33,440 --> 00:21:35,241 THEIR 40s OR YOUNGER. 448 00:21:35,241 --> 00:21:37,110 EQUIVALENT OF 58 DIAGNOSES EACH 449 00:21:37,110 --> 00:21:39,079 DAY WHICH IS QUITE A LARGE 450 00:21:39,079 --> 00:21:43,083 NUMBER FOR A CANCER THAT ONLY 451 00:21:43,083 --> 00:21:46,252 VERY RECENTLY WAS CONSIDERED AN 452 00:21:46,252 --> 00:21:49,623 OLD PERSON'S DISEASE. 453 00:21:49,623 --> 00:21:51,725 THERE'S SOME INTERESTING RACIAL 454 00:21:51,725 --> 00:21:53,627 AND ETHNIC VARIATION IN THE 455 00:21:53,627 --> 00:21:54,828 EARLY ONSET TRENDS. 456 00:21:54,828 --> 00:21:56,630 THIS FIGURE SHOWS INCIDENT RATES 457 00:21:56,630 --> 00:21:58,999 FOR THE FIVE BROADLY DEFINEDED 458 00:21:58,999 --> 00:22:00,900 RACIAL AND ETHNIC GROUPS FOR 459 00:22:00,900 --> 00:22:05,138 WHICH WE HAVE CANCER DATA. 460 00:22:05,138 --> 00:22:06,206 AND FOR EXAMPLE IN THE BLACK 461 00:22:06,206 --> 00:22:08,241 POPULATION, WHICH IS SHOWN IN 462 00:22:08,241 --> 00:22:10,110 ORANGE, RATES HAVE BEEN STEADY 463 00:22:10,110 --> 00:22:11,711 UNTIL JUST RECENTLY. 464 00:22:11,711 --> 00:22:13,747 SO ONLY BEGAN TO INCREASE IN THE 465 00:22:13,747 --> 00:22:18,551 LAST COUPLE OF YEARS. 466 00:22:18,551 --> 00:22:20,854 WHEREAS IN THE WHITE SHOWN IN 467 00:22:20,854 --> 00:22:23,523 BLUE, RATES HAVE BEEN STEADILY 468 00:22:23,523 --> 00:22:27,027 INCREASING SINCE THE MID '90s. 469 00:22:27,027 --> 00:22:30,263 AND THEN NATIVE AMERICANS, SO 470 00:22:30,263 --> 00:22:37,137 THIS IS AMERICAN INDIAN AND 471 00:22:37,137 --> 00:22:40,407 ALASKAN NATIVE HAVE HAD THE 472 00:22:40,407 --> 00:22:42,976 STEADIEST INCREASE SINCE 1998. 473 00:22:42,976 --> 00:22:44,377 THEIR RATES SURPASSED THE BLACK 474 00:22:44,377 --> 00:22:45,879 POPULATION TO HAVE THE HIGHEST 475 00:22:45,879 --> 00:22:52,085 EARLY ONSET RATES BY FAR. 476 00:22:52,085 --> 00:22:52,986 ANOTHER INTERESTING 477 00:22:52,986 --> 00:22:54,721 CHARACTERISTIC OF THE TREND I 478 00:22:54,721 --> 00:22:59,693 ALREADY TOUCHED ON EARLIER IS 479 00:22:59,693 --> 00:23:04,397 THE PROPONDERANCE OF RECTAL 480 00:23:04,397 --> 00:23:06,733 TUMORS WELL IN THE DISTAL COLON. 481 00:23:06,733 --> 00:23:09,636 I INCLUDE THE DIAGRAM HERE IN 482 00:23:09,636 --> 00:23:18,178 CASE YOU MAYBE HAVE FORGOT STEN 483 00:23:18,178 --> 00:23:28,722 YOUR ANATOMY AND SEEING THEM 2% 484 00:23:29,456 --> 00:23:30,824 PER YEAR WITH THE SMALL INCREASE 485 00:23:30,824 --> 00:23:34,327 OF PROXIMAL TUMORS OF .3% PER 486 00:23:34,327 --> 00:23:36,596 YEAR. 487 00:23:36,596 --> 00:23:39,599 AND BECAUSE OF THE STRONG BOTH 488 00:23:39,599 --> 00:23:43,570 COHORT EFFECT THESE CANCER 489 00:23:43,570 --> 00:23:44,437 SUBSITES ARE ALSO DRIVING THE 490 00:23:44,437 --> 00:23:46,539 INCREASE FOR MIDDLE AGE PEOPLE. 491 00:23:46,539 --> 00:23:49,609 EVEN IN PEOPLE 65 AND OLDER, 492 00:23:49,609 --> 00:23:51,845 RECTAL CANCER HAS BECOME THE 493 00:23:51,845 --> 00:23:54,180 SECOND MOST COMMON AMONG THESE 494 00:23:54,180 --> 00:23:57,717 CANCERS. 495 00:23:57,717 --> 00:23:59,686 SO SOMETHING THAT'S REALLY 496 00:23:59,686 --> 00:24:02,622 INTERESTING TO ME IS THAT THIS 497 00:24:02,622 --> 00:24:04,691 BIRTH COHORT EFFECT HAS 498 00:24:04,691 --> 00:24:08,361 COMPLETELY REVERSED A TREND THAT 499 00:24:08,361 --> 00:24:10,296 WAS HAPPENING 15 YEARS AGO. 500 00:24:10,296 --> 00:24:14,000 THERE WAS CONCERN ABOUT THIS 501 00:24:14,000 --> 00:24:17,170 TREND TOWARD MORE PROXIMAL COLON 502 00:24:17,170 --> 00:24:17,403 CANCERS. 503 00:24:17,403 --> 00:24:20,273 THE REASON THAT WAS CONCERNING 504 00:24:20,273 --> 00:24:23,109 IS BECAUSE PROXIMAL CANCERS ARE 505 00:24:23,109 --> 00:24:24,210 MORE DIFFICULT TO PREVENT 506 00:24:24,210 --> 00:24:26,780 THROUGH SCREENING AND HARDER TO 507 00:24:26,780 --> 00:24:29,082 TREAT. 508 00:24:29,082 --> 00:24:30,183 SURVIVAL RATES ARE LOWER. 509 00:24:30,183 --> 00:24:33,486 BUT THIS BOTH COHORT EFFECT HAS 510 00:24:33,486 --> 00:24:35,655 REVERSED THIS TREND. 511 00:24:35,655 --> 00:24:39,959 THIS IS -- THIS PLOT IS SHOWING 512 00:24:39,959 --> 00:24:43,763 A RATIO OF RECTAL CANCER VERSUS 513 00:24:43,763 --> 00:24:46,399 COLON CANCER OVER TIME IN MEN 514 00:24:46,399 --> 00:24:48,067 AND WOMEN. 515 00:24:48,067 --> 00:24:50,203 TODAY, THERE ARE ABOUT SIX 516 00:24:50,203 --> 00:24:53,072 RECTAL CANCERS FOR EVERY 10 517 00:24:53,072 --> 00:24:54,207 COLON CANCERS DIAGNOSED. 518 00:24:54,207 --> 00:24:56,409 AND THE REASON THAT THIS IS 519 00:24:56,409 --> 00:25:01,748 SURPRISING IS BECAUSE THE RECTUM 520 00:25:01,748 --> 00:25:03,950 ACCOUNTS FOR 10% OF THE TOTAL 521 00:25:03,950 --> 00:25:05,585 LARGE INTESTINE AND BECAUSE THIS 522 00:25:05,585 --> 00:25:12,892 IS ALL AGES, THERE'S AN WHY -- 523 00:25:12,892 --> 00:25:14,360 AN IMPACT AT SCREENING AND WORKS 524 00:25:14,360 --> 00:25:16,629 TO PREVENTING TUMORS IN THE 525 00:25:16,629 --> 00:25:18,198 RECTUM BECAUSE OF THEIR 526 00:25:18,198 --> 00:25:20,834 LOCATION. 527 00:25:20,834 --> 00:25:22,202 ANOTHER MORE CONCERNING 528 00:25:22,202 --> 00:25:24,938 CHARACTERISTIC OF THE EARLY 529 00:25:24,938 --> 00:25:29,075 ONSET TREND IS THE PREPONDERANCE 530 00:25:29,075 --> 00:25:30,777 OF ADVANCED STAGE DISEASE. 531 00:25:30,777 --> 00:25:33,479 THIS SHOWS INCIDENT RATES BY 532 00:25:33,479 --> 00:25:34,314 STAGE AT DIAGNOSIS. 533 00:25:34,314 --> 00:25:36,549 THESE ARE SUMMARY STAGE BECAUSE 534 00:25:36,549 --> 00:25:41,354 WE CAN'T LOOK AT AAJC STABLING 535 00:25:41,354 --> 00:25:43,022 WHICH IS MORE CLINICALLY 536 00:25:43,022 --> 00:25:44,791 RELEVANT BECAUSE OF IMPROVEMENTS 537 00:25:44,791 --> 00:25:47,627 IN STAGING OVER TIME. 538 00:25:47,627 --> 00:25:50,897 BUT THESE BASICALLY ALIGN WITH 539 00:25:50,897 --> 00:25:54,767 THE HAJC STAGING. 540 00:25:54,767 --> 00:25:56,703 THEY JUST HAVE BROADER 541 00:25:56,703 --> 00:25:57,003 CATEGORIES. 542 00:25:57,003 --> 00:25:59,105 SO THERE'S BEEN AN INCREASE IN 543 00:25:59,105 --> 00:26:02,208 INCIDENTS FOR BOTH REGIONAL AND 544 00:26:02,208 --> 00:26:04,244 DISTANT STAGE DISEASE OF 3% PER 545 00:26:04,244 --> 00:26:04,811 YEAR. 546 00:26:04,811 --> 00:26:06,379 IT'S A VERY STEEP INCREASE YEAR 547 00:26:06,379 --> 00:26:12,318 OVER YEAR IN RATES. 548 00:26:12,318 --> 00:26:14,721 AND THERE'S LOCALIZED STATE 549 00:26:14,721 --> 00:26:15,989 DISEASE HAS REMAINED FLAT. 550 00:26:15,989 --> 00:26:17,557 THIS IS PARTLY BECAUSE THIS 551 00:26:17,557 --> 00:26:19,759 POPULATION HAS NOT HISTORICALLY 552 00:26:19,759 --> 00:26:21,661 BEEN SCREENED. 553 00:26:21,661 --> 00:26:22,795 SO LOCALIZED DISEASE IS USUALLY 554 00:26:22,795 --> 00:26:25,565 ASYMPTOMATIC. 555 00:26:25,565 --> 00:26:28,201 BUT IT'S ALSO BECAUSE OF 556 00:26:28,201 --> 00:26:30,603 AVOIDABLE DELAYS IN DIAGNOSIS. 557 00:26:30,603 --> 00:26:33,740 THE MOST COMMON BEING A DELAY IN 558 00:26:33,740 --> 00:26:36,609 THE TIMING BETWEEN THE ONSET OF 559 00:26:36,609 --> 00:26:40,446 SYMPTOMS AND THE INITIAL MEDICAL 560 00:26:40,446 --> 00:26:41,481 CONTACT. 561 00:26:41,481 --> 00:26:46,019 BUT ALSO A CONTRIBUTOR TO THESE 562 00:26:46,019 --> 00:26:49,055 DELAYS IN DIAGNOSIS IS THE 563 00:26:49,055 --> 00:26:51,691 DIAGNOSIS RECTAL BLEEDING IS THE 564 00:26:51,691 --> 00:26:53,960 MOST COMMON SYMPTOM IN YOUNG 565 00:26:53,960 --> 00:26:55,795 PATIENTS AND THEY'LL OFTEN BE 566 00:26:55,795 --> 00:26:57,830 DIAGNOSED WITH HEMORRHOIDS WHICH 567 00:26:57,830 --> 00:27:01,701 IS THE HORSE, AND NOT THE ZEBRA. 568 00:27:01,701 --> 00:27:04,070 INSTEAD OF BEING FOLLOWED UP FOR 569 00:27:04,070 --> 00:27:07,073 CANCER BECAUSE THEY'RE YOUNG AND 570 00:27:07,073 --> 00:27:10,376 CANCER ISN'T EXPECTED. 571 00:27:10,376 --> 00:27:12,912 EARLY ONSET CANCERS DON'T APPEAR 572 00:27:12,912 --> 00:27:14,881 TO BE MORE AGGRESSIVE THOUGH. 573 00:27:14,881 --> 00:27:16,416 YOU MIGHT COME TO THAT 574 00:27:16,416 --> 00:27:18,651 CONCLUSION AND A LOT OF PEOPLE 575 00:27:18,651 --> 00:27:22,021 DID INITIALLY BUT THERE'S BEEN 576 00:27:22,021 --> 00:27:30,196 SEVERAL STUDIES AND STUDIES 577 00:27:30,196 --> 00:27:32,131 INDICATE EARLY ONSET DISEASE IS 578 00:27:32,131 --> 00:27:35,034 REALLY DRIVEN BY SPORADIC 579 00:27:35,034 --> 00:27:38,037 CANCERS MEANING CANCERS THAT 580 00:27:38,037 --> 00:27:40,773 DON'T HAVE GENETIC 581 00:27:40,773 --> 00:27:42,208 PREDISPOSITION AND ALSO THEY'RE 582 00:27:42,208 --> 00:27:45,845 BIO LOGICALLY VERY SIMILAR EARLY 583 00:27:45,845 --> 00:27:52,318 ONSET AND LATER ONSET DISEASE. 584 00:27:52,318 --> 00:27:54,320 SO THE INCREASING TREND IN 585 00:27:54,320 --> 00:27:57,590 PEOPLE IN MIDDLE AGE, AS YOU'D 586 00:27:57,590 --> 00:27:59,425 EXPECT, OR MAYBE NOT EXPECT 587 00:27:59,425 --> 00:28:02,195 BECAUSE THESE ARE SCREENING AGE 588 00:28:02,195 --> 00:28:03,730 BUT INDEED THE INCREASE IS 589 00:28:03,730 --> 00:28:11,304 CONFINED TO REGIONAL AND DISTANT 590 00:28:11,304 --> 00:28:13,206 STAGE AND THE MOST COMMON 591 00:28:13,206 --> 00:28:15,508 DIAGNOSIS FOR COLORECTAL CANCER 592 00:28:15,508 --> 00:28:16,809 OVER ALL ALL AGES COMBINED NOW 593 00:28:16,809 --> 00:28:17,577 IS STAGE 3. 594 00:28:17,577 --> 00:28:22,048 I HAVE TO TELL YOU WHEN I 595 00:28:22,048 --> 00:28:23,483 REALIZED THIS I WAS SHOCKED 596 00:28:23,483 --> 00:28:25,485 BECAUSE FOR OTHER SCREENABLE 597 00:28:25,485 --> 00:28:27,754 CANCERS LIKE BREAST AND CERVIX, 598 00:28:27,754 --> 00:28:29,088 STAGE 1 IS MOST COMMON. 599 00:28:29,088 --> 00:28:36,329 SO THIS IS SURPRISING. 600 00:28:36,329 --> 00:28:39,165 THIS BAR CHART SHOWS STAGE 601 00:28:39,165 --> 00:28:39,866 DISTRIBUTION IN THE MOST RECENT 602 00:28:39,866 --> 00:28:43,469 FIVE YEARS OF DATA AND NOT 603 00:28:43,469 --> 00:28:45,238 SURPRISINGLY PEOPLE UNDER 50, SO 604 00:28:45,238 --> 00:28:48,007 SHOWN IN THE BLUE BARS, ARE 605 00:28:48,007 --> 00:28:49,976 LEAST LIKELY TO BE DIAGNOSED 606 00:28:49,976 --> 00:28:53,046 WITH LOCALIZED STAGE. 607 00:28:53,046 --> 00:28:55,214 ONLY 1 IN 4 OF THESE PATIENTS 608 00:28:55,214 --> 00:28:58,317 ARE DIAGNOSED EARLY VERSUS 1 IN 609 00:28:58,317 --> 00:29:03,456 3 PEOPLE 50 AND OLDER. 610 00:29:03,456 --> 00:29:06,159 HOWEVER, YOUNG PATIENTS DO TEND 611 00:29:06,159 --> 00:29:12,231 TO HAVE HIGHER SURVIVAL RATES 612 00:29:12,231 --> 00:29:14,067 BECAUSE THEY'RE USUALLY HEALTHY 613 00:29:14,067 --> 00:29:18,204 AND TREATED AGGRESSIVELY WHICH 614 00:29:18,204 --> 00:29:22,208 IS SOMEWHAT CONTROVERSIAL. 615 00:29:22,208 --> 00:29:23,342 NEVERTHELESS, DEATH RATES IN 616 00:29:23,342 --> 00:29:27,580 PEOPLE UNDER 55 ARE INCREASING 617 00:29:27,580 --> 00:29:32,385 AFTER MANY DECADES OF DECLINES. 618 00:29:32,385 --> 00:29:33,519 THESE FIGURES SHOW TRENDS IN 619 00:29:33,519 --> 00:29:36,155 DEATH RATES IN PEOPLE YOUNGER 620 00:29:36,155 --> 00:29:38,758 THAN 55 OVER ALL AND BY RACE. 621 00:29:38,758 --> 00:29:40,026 AND THE REASON THERE'S ONLY 622 00:29:40,026 --> 00:29:43,262 BLACK AND WHITE RACE HERE IS 623 00:29:43,262 --> 00:29:46,265 BECAUSE WHEN WE LOOK AT 624 00:29:46,265 --> 00:29:48,134 HISTORICAL MORTALITY DATA WE 625 00:29:48,134 --> 00:29:48,701 ONLY HAVE THESE THREE RACE 626 00:29:48,701 --> 00:29:54,006 STRATIFICATIONS. 627 00:29:54,006 --> 00:29:55,441 THESE PATTERNS ARE SIMILAR TO 628 00:29:55,441 --> 00:29:57,043 WHAT WE SEE FOR INCIDENTS. 629 00:29:57,043 --> 00:29:59,412 THE INCREASE IN DEATH RATES IN 630 00:29:59,412 --> 00:30:02,181 WHITE PEOPLE IS STEEPER THAN THE 631 00:30:02,181 --> 00:30:04,183 OVER ALL INCREASE AND WE'RE 632 00:30:04,183 --> 00:30:07,420 STILL SEEING DECLINES IN THE 633 00:30:07,420 --> 00:30:08,721 DEATH RATE IN THE BLACK 634 00:30:08,721 --> 00:30:12,658 POPULATION UNDER 55. 635 00:30:12,658 --> 00:30:14,293 THIS IS A LITTLE BIT DATED 636 00:30:14,293 --> 00:30:17,163 BECAUSE THIS IS OUR FIRST STUDY 637 00:30:17,163 --> 00:30:20,399 SHOWING THE INCREASE IN EARLY 638 00:30:20,399 --> 00:30:22,502 ONSET DEATH RATES BUT THE 639 00:30:22,502 --> 00:30:24,437 PATTERNS ARE STILL HOLDING 640 00:30:24,437 --> 00:30:25,671 THOUGH THE INCREASE IN THE WHITE 641 00:30:25,671 --> 00:30:27,607 POPULATION IS A LITTLE BIT 642 00:30:27,607 --> 00:30:29,976 STEEPER NOW ALMOST 2% PER YEAR 643 00:30:29,976 --> 00:30:31,611 INCREASE IN DEATH RATES. 644 00:30:31,611 --> 00:30:34,180 AND THE DECREASE IN THE YOUNG 645 00:30:34,180 --> 00:30:37,183 BLACK POPULATION HAS SLOWED TO 646 00:30:37,183 --> 00:30:43,156 ABOUT .6%. 647 00:30:43,156 --> 00:30:46,025 SO, AS A RESULT, COLORECTAL 648 00:30:46,025 --> 00:30:47,627 CANCER HAS BECOME THE MOST 649 00:30:47,627 --> 00:30:49,295 COMMON CAUSE OF CANCER DEATH IN 650 00:30:49,295 --> 00:30:52,665 MEN UNDER 50 AND THE SECOND MOST 651 00:30:52,665 --> 00:30:55,168 COMMON CAUSE OF CANCER DEATH IN 652 00:30:55,168 --> 00:30:58,337 WOMEN UNDER 50 AFTER BREAST 653 00:30:58,337 --> 00:31:00,006 CANCER, WHICH STILL HAS MANY 654 00:31:00,006 --> 00:31:02,208 MORE DEATHS ABOUT 2,000 MORE 655 00:31:02,208 --> 00:31:06,012 DEATHS THAN COLORECTAL CANCER. 656 00:31:06,012 --> 00:31:08,414 THIS IS ALSO THOUGH AS I'M SURE 657 00:31:08,414 --> 00:31:12,018 YOU'LL NOTICE BECAUSE OF STEEP 658 00:31:12,018 --> 00:31:15,087 DECLINES IN LUNG CANCER DEATHS, 659 00:31:15,087 --> 00:31:17,056 SHOWN IN GREEN, BECAUSE THERE'S 660 00:31:17,056 --> 00:31:21,994 SUCCESSFUL TA BOBACCO CONTROL. 661 00:31:21,994 --> 00:31:24,830 YOU MIGHT NOTICE IN THE FIGURES, 662 00:31:24,830 --> 00:31:27,066 COLON CANCER IS SHOWN IN BLUE 663 00:31:27,066 --> 00:31:30,503 AND DEATHS -- THE NUMBER OF 664 00:31:30,503 --> 00:31:36,842 DEATHS FROM COLORECTAL CANCER 665 00:31:36,842 --> 00:31:39,912 STARTED INCREASING IN 1990 AND 666 00:31:39,912 --> 00:31:42,782 SHOWS INCONSISTENT FROM WHAT YOU 667 00:31:42,782 --> 00:31:44,717 SAID OF INCREASES STARTING IN 668 00:31:44,717 --> 00:31:45,785 THE 2000s. 669 00:31:45,785 --> 00:31:47,587 BECAUSE THE POPULATION IS AGING 670 00:31:47,587 --> 00:31:49,822 AND GROWING, THERE HAS TO BE A 671 00:31:49,822 --> 00:31:54,093 VERY LARGE RATE OF DECREASE IN 672 00:31:54,093 --> 00:31:55,761 ORDER FOR THERE NOT TO BE AN 673 00:31:55,761 --> 00:31:57,663 INCREASE IN THE NUMBER OF CANCER 674 00:31:57,663 --> 00:31:57,897 DEATHS. 675 00:31:57,897 --> 00:31:58,531 SO THIS IS TRUE FOR CASES AS 676 00:31:58,531 --> 00:32:04,670 WELL. 677 00:32:04,670 --> 00:32:07,206 THIS IS WHY WE HAVE DECREASING 678 00:32:07,206 --> 00:32:10,243 OVER ALL CANCER INCIDENTS YEAR 679 00:32:10,243 --> 00:32:12,211 OVER YEAR SINCE 1981 BUT THE 680 00:32:12,211 --> 00:32:12,845 NUMBER OF CANCER DEATHS 681 00:32:12,845 --> 00:32:13,479 CONTINUES TO INCREASE OVER THE 682 00:32:13,479 --> 00:32:23,589 YEAR. 683 00:32:31,230 --> 00:32:33,266 WE STARTED LOOKING AT INCREASES 684 00:32:33,266 --> 00:32:35,167 RATES IN 2009. 685 00:32:35,167 --> 00:32:38,204 WE WONDERED WHETHER THIS WAS A 686 00:32:38,204 --> 00:32:40,673 GLOBAL PHENOMENON OR CONFINED TO 687 00:32:40,673 --> 00:32:40,906 THE U.S. 688 00:32:40,906 --> 00:32:45,111 SO WE COLLABORATED WITH 689 00:32:45,111 --> 00:32:50,182 RESEARCHERS AT TO LOOK AT THE 690 00:32:50,182 --> 00:32:52,918 CI5 DATA INCLUDING MANY 691 00:32:52,918 --> 00:32:56,022 COUNTRIES, 43 IN THIS ANALYSIS, 692 00:32:56,022 --> 00:32:57,690 THOUGH I WILL SAY MOST 693 00:32:57,690 --> 00:32:59,325 LOW-INCOME COUNTRIES ARE NOT 694 00:32:59,325 --> 00:33:00,926 INCLUDED AND MANY MANY MIDDLE 695 00:33:00,926 --> 00:33:02,528 INCOME COUNTRIES ARE ALSO NOT 696 00:33:02,528 --> 00:33:04,664 INCLUDED BECAUSE THEY DON'T HAVE 697 00:33:04,664 --> 00:33:06,532 THE RESOURCES TO COLLECT CANCER 698 00:33:06,532 --> 00:33:11,737 INFORMATION. 699 00:33:11,737 --> 00:33:14,140 WE DID THIS STUDY PUBLISHED IN 700 00:33:14,140 --> 00:33:15,174 2019 WE IDENTIFIED EIGHT 701 00:33:15,174 --> 00:33:19,245 COUNTRIES IN ADDITION TO THE 702 00:33:19,245 --> 00:33:22,181 U.S. WHERE THERE WAS INCREASING 703 00:33:22,181 --> 00:33:24,016 EARLY ONSET DISEASE ALONGSIDE 704 00:33:24,016 --> 00:33:27,353 STABLE OR DECLINING RATES IN 705 00:33:27,353 --> 00:33:32,725 PEOPLE 50 AND OLDER. 706 00:33:32,725 --> 00:33:36,062 AND THEN JUST A COUPLE MONTHS 707 00:33:36,062 --> 00:33:37,296 AGO WE PUBLISHED AN UPDATE OF 708 00:33:37,296 --> 00:33:38,297 THE ANALYSIS. 709 00:33:38,297 --> 00:33:41,867 WE WERE ABLE TO ADD SIX MORE 710 00:33:41,867 --> 00:33:43,269 COUNTRIES PLUS THE 711 00:33:43,269 --> 00:33:45,571 U.S. TERRITORY OF PUERTO RICO 712 00:33:45,571 --> 00:33:46,706 AND ALSO FIVE ADDITIONAL YEARS 713 00:33:46,706 --> 00:33:51,510 OF DATA. 714 00:33:51,510 --> 00:33:54,180 THIS WAS ALSO COLLABORATION WITH 715 00:33:54,180 --> 00:33:56,916 RESEARCHERS AT IARC. 716 00:33:56,916 --> 00:33:59,318 SO IN THIS ANALYSIS WE 717 00:33:59,318 --> 00:34:03,422 IDENTIFIED 12 COUNTRIES IN 718 00:34:03,422 --> 00:34:05,658 ADDITION TO THE U.S. THAT 719 00:34:05,658 --> 00:34:07,126 EXHIBITED THIS UNIQUE INCREASE 720 00:34:07,126 --> 00:34:09,295 IN EARLY ONSET DISEASE AS WELL 721 00:34:09,295 --> 00:34:12,598 AS THE TERRITORY OF PUERTO RICO. 722 00:34:12,598 --> 00:34:17,737 AND YOU MAY HAVE NOTICED IN THE 723 00:34:17,737 --> 00:34:19,672 LAST SLIDE WE WERE ONLY ABLE TO 724 00:34:19,672 --> 00:34:21,140 ANALYZE THE U.K. IN THE LAST 725 00:34:21,140 --> 00:34:22,708 STUDY BUT IN THE CURRENT STUDY 726 00:34:22,708 --> 00:34:24,844 WERE WERE ABLE TO BREAK OUT 727 00:34:24,844 --> 00:34:27,079 ENGLAND AND SCOTLAND SO I HAVE 728 00:34:27,079 --> 00:34:29,014 NOTED SCOTLAND AS A NEW FINDING 729 00:34:29,014 --> 00:34:31,851 BECAUSE WHEN YOU LOOK AT DATA 730 00:34:31,851 --> 00:34:35,688 FOR THE U.K. OVER ALL IT'S 731 00:34:35,688 --> 00:34:40,593 DRIVEN BY ENGLAND. 732 00:34:40,593 --> 00:34:42,361 SO THESE FIGURES ARE EXAMPLES OF 733 00:34:42,361 --> 00:34:46,298 SOME OF THE STEEPEST INCREASES 734 00:34:46,298 --> 00:34:49,668 WE FOUND IN THE NEW STUDY. 735 00:34:49,668 --> 00:34:52,238 INCREASES OF 3% TO 4% PER YEAR. 736 00:34:52,238 --> 00:34:54,407 AND THE COUNTRIES ON THE LEFT 737 00:34:54,407 --> 00:34:58,544 ARE COUNTRIES THAT WE IDENTIFIED 738 00:34:58,544 --> 00:35:01,914 IN THE LAST STUDY SO THEY'RE NOT 739 00:35:01,914 --> 00:35:03,849 NEW WITH THE EXCEPTION OF PUERTO 740 00:35:03,849 --> 00:35:04,049 RICO. 741 00:35:04,049 --> 00:35:06,919 PUERTO RICO WAS NOT ABLE TO BE 742 00:35:06,919 --> 00:35:09,188 ANALYZED LAST TIME BECAUSE AS 743 00:35:09,188 --> 00:35:11,590 YOU'LL NOTICE FROM THE SHORT 744 00:35:11,590 --> 00:35:15,327 LINES, WE ONLY HAD ENOUGH 745 00:35:15,327 --> 00:35:18,063 LONGITUDINAL DATA RECENTLY IN 746 00:35:18,063 --> 00:35:19,698 ORDER TO ANALYZE TRENDS. 747 00:35:19,698 --> 00:35:21,600 THESE FIGURES SHOW TRENDS IN 748 00:35:21,600 --> 00:35:25,404 YOUNG ADULTS -- 50 IN RED AND 50 749 00:35:25,404 --> 00:35:33,512 AND OLDER IN BLUE. 750 00:35:33,512 --> 00:35:35,548 WE HAVE THE AVERAGE ANNUAL 751 00:35:35,548 --> 00:35:38,050 PERCENT CHANGE IN THE LAST 752 00:35:38,050 --> 00:35:40,085 DECADE SHOWN UNDERNEATH. 753 00:35:40,085 --> 00:35:42,822 INTERESTINGLY THE STEEP INCREASE 754 00:35:42,822 --> 00:35:46,826 IN PUERTO RICO -- PUERTO RICO IS 755 00:35:46,826 --> 00:35:47,893 99% HISPANIC. 756 00:35:47,893 --> 00:35:51,931 IT'S IN LINE WITH RECENT TRENDS 757 00:35:51,931 --> 00:35:55,367 AMONG HISPANIC PEOPLE ALTHOUGH 758 00:35:55,367 --> 00:35:56,469 IT'S ONLY IN THE MORE RECENT 759 00:35:56,469 --> 00:35:58,737 FIVE YEARS OR SO THAT RATES HAVE 760 00:35:58,737 --> 00:36:00,306 REALLY TAKEN OFF HIGHER. 761 00:36:00,306 --> 00:36:01,540 THEY WERE MORE STABLE. 762 00:36:01,540 --> 00:36:04,276 IT WILL BE INTERESTING TO FOLLOW 763 00:36:04,276 --> 00:36:10,015 THIS TREND IN PUERTO RICO. 764 00:36:10,015 --> 00:36:12,284 AND THIS SLIDE SHOWS NEWLY 765 00:36:12,284 --> 00:36:13,118 IDENTIFIED COUNTRIES. 766 00:36:13,118 --> 00:36:16,522 SO, WE FOUND THIS TREND IN 767 00:36:16,522 --> 00:36:18,224 ISRAEL, ARGENTINA, NORWAY AND 768 00:36:18,224 --> 00:36:23,762 FRANCE. 769 00:36:23,762 --> 00:36:25,464 SOME OF THESE COUNTRIES WE 770 00:36:25,464 --> 00:36:28,467 WEREN'T ABLE TO USE 100% 771 00:36:28,467 --> 00:36:29,869 POPULATION COVERAGE AND THAT'S 772 00:36:29,869 --> 00:36:32,738 THE ASTERISK IN ARGENTINA SO 773 00:36:32,738 --> 00:36:34,139 THIS IS SUB NATIONAL DATA. 774 00:36:34,139 --> 00:36:37,476 ALL THE COUNTRIES HAD STEEP 775 00:36:37,476 --> 00:36:42,348 INCREASES OF 2% TO 3.5% PER YEAR 776 00:36:42,348 --> 00:36:45,651 FOR EARLY ONSET DISEASE. 777 00:36:45,651 --> 00:36:49,455 AND THE REASON THE AVERAGE 778 00:36:49,455 --> 00:36:52,691 ANNUAL PERCENT CHANGE IS MISSING 779 00:36:52,691 --> 00:36:54,393 FROM ARGENTINA, NORWAY AND 780 00:36:54,393 --> 00:36:55,294 FRANCE IS BECAUSE RATES IN 50 781 00:36:55,294 --> 00:37:02,301 AND OLDER ARE STABLE. 782 00:37:02,301 --> 00:37:04,503 IN SEVERAL COUNTRIES RATES WERE 783 00:37:04,503 --> 00:37:07,206 INCREASING IN BOTH AGE GROUPS 784 00:37:07,206 --> 00:37:10,876 UNDER 50 AND 50 AND OLDER. 785 00:37:10,876 --> 00:37:14,680 BUT THE INCREASE IN THE YOUNGER 786 00:37:14,680 --> 00:37:18,183 ADULTS OF WAS MUCH STEEPER. 787 00:37:18,183 --> 00:37:21,353 THESE ARE TWO OF THE MORE 788 00:37:21,353 --> 00:37:26,492 EXTREME SAMPLES IN SWEDEN AND 789 00:37:26,492 --> 00:37:30,195 CHILE. 790 00:37:30,195 --> 00:37:33,265 COLORECTAL CANCER IS A PROXY FOR 791 00:37:33,265 --> 00:37:34,833 GLOBAL DEVELOPMENT ON THE 792 00:37:34,833 --> 00:37:38,203 ECONOMIC SCALE BECAUSE LOW AND 793 00:37:38,203 --> 00:37:41,807 MIDDLE INCOME COUNTRIES THAT ARE 794 00:37:41,807 --> 00:37:45,744 DEVELOPING AND ADOPTING THOSE 795 00:37:45,744 --> 00:37:47,713 RISK FACTORS LIKE GAINING 796 00:37:47,713 --> 00:37:51,283 WEIGHT, EATING MORE RED MEAT, 797 00:37:51,283 --> 00:37:52,885 SMOKING, THEY'RE ASSOCIATED WITH 798 00:37:52,885 --> 00:37:55,521 A MORE WESTERN LIFESTYLE. 799 00:37:55,521 --> 00:37:57,222 SO, IT'S VERY COMMON FOR THESE 800 00:37:57,222 --> 00:38:01,527 COUNTRIES TO HAVE INCREASING 801 00:38:01,527 --> 00:38:04,330 INCIDENCE RATES THOUGH IT 802 00:38:04,330 --> 00:38:09,335 DOESN'T APPLY TO SWEDEN AND 803 00:38:09,335 --> 00:38:17,109 CHILE BUT COLORECTAL CANCER IS A 804 00:38:17,109 --> 00:38:23,515 PROXY FOR GLOBAL DEVELOPMENT AND 805 00:38:23,515 --> 00:38:25,050 PEER COUNTRIES AND RATES WHERE 806 00:38:25,050 --> 00:38:27,686 OLDER ADULT DECLINING BUT DON'T 807 00:38:27,686 --> 00:38:29,655 SEE AN INCREASE IN EARLY ONSET 808 00:38:29,655 --> 00:38:29,855 THESE. 809 00:38:29,855 --> 00:38:33,792 WE SAW THIS PATTERN IN SPAIN, 810 00:38:33,792 --> 00:38:40,099 ITALY AND AUSTRIA. 811 00:38:40,099 --> 00:38:40,733 IT WILL BE INTERESTING TO WATCH 812 00:38:40,733 --> 00:38:41,734 THE COUNTRIES AND SEE IF THE 813 00:38:41,734 --> 00:38:43,802 STABLE RATES HOLD OR ULTIMATE HI 814 00:38:43,802 --> 00:38:45,771 INCREASE BECAUSE THE TIMING DOES 815 00:38:45,771 --> 00:38:56,315 DEFER IN SOME OF THE COUNTRIES. 816 00:38:57,816 --> 00:39:00,686 WE'LL LOOK AT POTENTIAL CAUSES 817 00:39:00,686 --> 00:39:01,220 AND MITIGATING THE RISING 818 00:39:01,220 --> 00:39:07,626 BURDEN. 819 00:39:07,626 --> 00:39:08,594 THE FIRST QUESTION EVERYONE ASKS 820 00:39:08,594 --> 00:39:10,863 IS WHY IS THIS HAPPENING? 821 00:39:10,863 --> 00:39:14,299 THE FIRST PLACE TO LOOK IS 822 00:39:14,299 --> 00:39:18,637 ESTABLISHED RISK FACTORS FOR THE 823 00:39:18,637 --> 00:39:20,906 DISEASE AND THIS SHOWS WELL 824 00:39:20,906 --> 00:39:24,009 ESTABLISHED RISK FACTORS FOR 825 00:39:24,009 --> 00:39:24,977 COLORECTAL CANCER. 826 00:39:24,977 --> 00:39:26,545 ON THE FIRST HALF ARE FACTORS 827 00:39:26,545 --> 00:39:27,880 THAT INCREASE RISK AND THEN 828 00:39:27,880 --> 00:39:30,015 THERE'S A COUPLE PROTECTIVE 829 00:39:30,015 --> 00:39:31,750 FACTORS AND THEY'RE SHOWN WITH 830 00:39:31,750 --> 00:39:35,487 THEIR RELATIVE RISK ESTIMATE AS 831 00:39:35,487 --> 00:39:36,088 WELL AS POPULATION PREVALENCE 832 00:39:36,088 --> 00:39:37,423 TRENDS. 833 00:39:37,423 --> 00:39:42,528 SO THE FIRST THING THAT EVERYONE 834 00:39:42,528 --> 00:39:45,464 THINKS ABOUT IS WE USED TO SEE 835 00:39:45,464 --> 00:39:47,199 EPIDEMIC AND KNOW IT'S BEEN 836 00:39:47,199 --> 00:39:50,769 INCREASING SINCE THE 1970s WITH 837 00:39:50,769 --> 00:39:52,805 CUMULATIVE EXCESS BODY WEIGHT 838 00:39:52,805 --> 00:39:54,973 AMONG YOUNGER GENERATIONS. 839 00:39:54,973 --> 00:39:58,210 THIS IS CERTAINLY SOMETHING TO 840 00:39:58,210 --> 00:40:00,512 LOOK INTO AS WELL AS OUR MORE 841 00:40:00,512 --> 00:40:04,016 SEDENTARY LIFESTYLE. 842 00:40:04,016 --> 00:40:06,251 PHYSICAL ACTIVITY OR LACK IT 843 00:40:06,251 --> 00:40:12,057 THEREOF ASSOCIATED WITH COLON 844 00:40:12,057 --> 00:40:14,059 CANCER BUT NOT ASSOCIATED WITH 845 00:40:14,059 --> 00:40:14,526 RECTAL CANCER. 846 00:40:14,526 --> 00:40:20,299 AT LEAST IN STUDIES OF OLDER 847 00:40:20,299 --> 00:40:21,233 COHORTS AND THAT'S SOMETHING I 848 00:40:21,233 --> 00:40:22,768 WANTED TO POINT OUT IN THE 849 00:40:22,768 --> 00:40:23,202 TABLE. 850 00:40:23,202 --> 00:40:24,470 ALL THESE ESTABLISHED RISK 851 00:40:24,470 --> 00:40:26,672 FACTORS ARE BASED ON DISEASE IN 852 00:40:26,672 --> 00:40:28,040 OLDER ADULTS. 853 00:40:28,040 --> 00:40:30,943 AND SO THEY MAY OR MAY NOT BE 854 00:40:30,943 --> 00:40:31,643 ASSOCIATED WITH EARLY ONSET 855 00:40:31,643 --> 00:40:41,620 DISEASE. 856 00:40:41,620 --> 00:40:44,790 A GROUP AT THE UNIVERSITY OF 857 00:40:44,790 --> 00:40:46,592 WASHINGTON PUBLISHED BETWEEN 858 00:40:46,592 --> 00:40:49,194 ESTABLISHED RISK FACTORS AND 859 00:40:49,194 --> 00:40:51,063 EARLY ONSET COLORECTAL CANCER 860 00:40:51,063 --> 00:40:53,599 USING THE NURSES HEALTH STUDY TO 861 00:40:53,599 --> 00:40:53,799 DATE. 862 00:40:53,799 --> 00:40:57,970 IN THIS STUDY THEY WERE LOOKING 863 00:40:57,970 --> 00:41:01,173 AT WHETHER OBESITY WAS 864 00:41:01,173 --> 00:41:02,407 ASSOCIATED WITH AN INCREASED 865 00:41:02,407 --> 00:41:02,641 RISK. 866 00:41:02,641 --> 00:41:05,177 THIS COHORT IS ONLY WOMEN. 867 00:41:05,177 --> 00:41:08,213 SO THIS FINDING IS COMBINED TO 868 00:41:08,213 --> 00:41:09,248 WOMEN. 869 00:41:09,248 --> 00:41:12,785 BUT THEY FOUND A 20% HIGHER RISK 870 00:41:12,785 --> 00:41:16,488 WITH EVERY FIVE UNITS OF BMI. 871 00:41:16,488 --> 00:41:20,058 THIS IS CONSISTENT WITH THE 872 00:41:20,058 --> 00:41:25,464 ASSOCIATION FOR OLDER ADULTS. 873 00:41:25,464 --> 00:41:28,000 HOWEVER, IT'S IMPORTANT TO 874 00:41:28,000 --> 00:41:29,168 REALIZE OBESITY AT LEAST IN 875 00:41:29,168 --> 00:41:33,338 OLDER ADULTS IS MUCH MORE 876 00:41:33,338 --> 00:41:34,706 STRONGLY ASSOCIATED WITH COLON 877 00:41:34,706 --> 00:41:38,510 CANCER THAN WITH RECTAL CANCER. 878 00:41:38,510 --> 00:41:42,181 SO, IF EXCESS BODY WEIGHT WAS 879 00:41:42,181 --> 00:41:45,851 THE SOLE CAUSE OF THE INCREASE, 880 00:41:45,851 --> 00:41:47,786 YOU'D EXPECT IT TO BE DRIVEN BY 881 00:41:47,786 --> 00:41:55,761 COLON CANCER AND NOT RECTAL 882 00:41:55,761 --> 00:41:56,962 CANCER, WHICH IS THE PATTERN 883 00:41:56,962 --> 00:41:57,863 WE'RE SEEING. 884 00:41:57,863 --> 00:41:59,364 AND THEY'RE LOOKING AT WHETHER 885 00:41:59,364 --> 00:42:03,402 SEDENTARY LIFESTYLE IN TERMS OF 886 00:42:03,402 --> 00:42:05,838 TV VIEWING WAS ASSOCIATED WITH 887 00:42:05,838 --> 00:42:06,939 EXCESS RISK. 888 00:42:06,939 --> 00:42:09,708 TV VIEWING IS THE SEDENTARY 889 00:42:09,708 --> 00:42:11,176 BEHAVIOR MOST STRONGLY 890 00:42:11,176 --> 00:42:15,047 ASSOCIATED WITH HARMS TO HEALTH. 891 00:42:15,047 --> 00:42:17,382 AND THEY FOUND THE HIGHER 892 00:42:17,382 --> 00:42:18,851 ELEVATED RISK. 893 00:42:18,851 --> 00:42:21,820 69% INCREASED RISK FOR WOMEN WHO 894 00:42:21,820 --> 00:42:25,157 WATCHED MORE THAN 14 HOURS OF TV 895 00:42:25,157 --> 00:42:27,926 PER WEEK COMPARED TO WOMEN WHO 896 00:42:27,926 --> 00:42:29,661 WERE WATCHING 7 OR FEWER HOURS 897 00:42:29,661 --> 00:42:32,865 OF TV. 898 00:42:32,865 --> 00:42:35,467 AGAIN, IMPORTANT TO REALIZE IN 899 00:42:35,467 --> 00:42:37,603 OLDER ADULTS THIS WOULD NOT BE 900 00:42:37,603 --> 00:42:43,809 ASSOCIATED WITH RECTAL CANCER. 901 00:42:43,809 --> 00:42:46,078 SO, IT DOESN'T APPEAR AS THOUGH 902 00:42:46,078 --> 00:42:47,312 OUR ESTABLISHED RISK FACTORS CAN 903 00:42:47,312 --> 00:42:52,584 AT LEAST FULLY EXPLAIN WHAT'S 904 00:42:52,584 --> 00:42:55,053 HAPPENING WITH THOSE COHORT 905 00:42:55,053 --> 00:42:56,455 EFFECT AND WHY RATES ARE 906 00:42:56,455 --> 00:42:56,755 INCREASING. 907 00:42:56,755 --> 00:42:59,391 THERE'S BEEN A FLURRY OF 908 00:42:59,391 --> 00:43:02,227 RESEARCH THINKING OUTSIDE THE 909 00:43:02,227 --> 00:43:06,198 BOX LOOKING AT VARIOUS EXPOSURES 910 00:43:06,198 --> 00:43:08,267 FROM ANTIBIOTIC USE TO BREAST 911 00:43:08,267 --> 00:43:11,603 FEEDING TO IN UTERO EXPOSURES, 912 00:43:11,603 --> 00:43:15,274 POLLUTANTS IN OUR FOOD AND 913 00:43:15,274 --> 00:43:25,083 WATER, AS WELL AS MICROPLASTICS. 914 00:43:25,083 --> 00:43:25,651 NOTHING DEFINITIVE HAS BEEN 915 00:43:25,651 --> 00:43:28,320 ESTABLISHED. 916 00:43:28,320 --> 00:43:30,622 THERE'S ALSO A LOT OF WORK WITH 917 00:43:30,622 --> 00:43:34,393 THE GUT MICROBIOME AND HOW THIS 918 00:43:34,393 --> 00:43:37,462 MIGHT INFLUENCE THE COLONIC 919 00:43:37,462 --> 00:43:40,532 MUCOSA WHICH PROTECTS US FROM 920 00:43:40,532 --> 00:43:41,767 DISEASE IN THE COLON. 921 00:43:41,767 --> 00:43:44,569 I THINK WE'RE GOING HEAR MORE 922 00:43:44,569 --> 00:43:45,837 FROM DR. MARKOWITZ ABOUT THIS IN 923 00:43:45,837 --> 00:43:53,345 THE NEXT SECTION. 924 00:43:53,345 --> 00:43:56,782 SO, WHILE WE AWAIT THE MORE 925 00:43:56,782 --> 00:43:58,150 DEFINITIVE CAUSE OF WHAT'S 926 00:43:58,150 --> 00:44:01,086 HAPPENING HERE, WE HAD A RAPIDLY 927 00:44:01,086 --> 00:44:02,254 INCREASING BURDEN OF DISEASE 928 00:44:02,254 --> 00:44:07,826 SHIFTING TO OUR MOST PRODUCTIVE 929 00:44:07,826 --> 00:44:08,093 CITIZENS. 930 00:44:08,093 --> 00:44:11,964 WE ALSO KNOW WE HAD AN EFFECTIVE 931 00:44:11,964 --> 00:44:14,933 SCREENING TEST THAT NOT ONLY 932 00:44:14,933 --> 00:44:16,268 PREVENTS CANCER DEATH BUT ALSO 933 00:44:16,268 --> 00:44:16,969 CAN PREVENT CANCER AT LEAST IN 934 00:44:16,969 --> 00:44:20,539 OLDER ADULTS. 935 00:44:20,539 --> 00:44:23,942 NOTABLY AMONG PEOPLE DIAGNOSED 936 00:44:23,942 --> 00:44:27,079 BEFORE 50, ALMOST HALF ARE IN 937 00:44:27,079 --> 00:44:30,615 PEOPLE IN THEIR LATE 40s. 938 00:44:30,615 --> 00:44:35,454 AND AN ADDITIONAL NEARLY 30% OF 939 00:44:35,454 --> 00:44:37,589 EARLY ONSET PATIENTS HAVE A 940 00:44:37,589 --> 00:44:41,793 FAMILY HISTORY OF THE DISEASE OR 941 00:44:41,793 --> 00:44:45,564 FAMILY HISTORY OF ADENOMAS OR 942 00:44:45,564 --> 00:44:47,265 GENETIC PREDISPOSITION. 943 00:44:47,265 --> 00:44:49,201 AND WE'LL HEAR MORE ABOUT THIS 944 00:44:49,201 --> 00:44:51,403 FROM DR. MARKOWITZ. 945 00:44:51,403 --> 00:44:53,839 PEOPLE IN THIS HIGHER RISK 946 00:44:53,839 --> 00:44:55,807 CATEGORY ARE RECOMMENDED TO 947 00:44:55,807 --> 00:44:56,408 START SCREENING EARLIER THAN 948 00:44:56,408 --> 00:45:00,846 AVERAGE RISK. 949 00:45:00,846 --> 00:45:03,682 SO THE AGE TO BEGIN SCREENING 950 00:45:03,682 --> 00:45:05,250 WAS LOWERED FROM 50 TO 45 YEARS 951 00:45:05,250 --> 00:45:08,854 FOR AVERAGE RISK ADULTS BY THE 952 00:45:08,854 --> 00:45:10,922 AMERICAN CANCER SOCIETY IN 2018 953 00:45:10,922 --> 00:45:14,559 AND THEN BY THE U.S. PREVENTIVE 954 00:45:14,559 --> 00:45:22,200 SERVICES TASK FORCE IN 2021. 955 00:45:22,200 --> 00:45:23,902 BOTH WERE QUALIFIED 956 00:45:23,902 --> 00:45:24,269 RECOMMENDATIONS. 957 00:45:24,269 --> 00:45:26,872 AT THE TIME THERE WAS EMPIRICAL 958 00:45:26,872 --> 00:45:28,407 EVIDENCE TO SHOW SCREENING WOULD 959 00:45:28,407 --> 00:45:32,811 BE EFFECTIVE IN PEOPLE UNDER 50 960 00:45:32,811 --> 00:45:36,048 AND IN FACT THERE WAS A LOT OF 961 00:45:36,048 --> 00:45:38,517 CRITICISM IN 2018 ACS WHEN THEY 962 00:45:38,517 --> 00:45:44,523 FIRST LOWERED THE AGE TO SCREEN. 963 00:45:44,523 --> 00:45:46,725 BUT I'M HAPPY TO REPORT IN THE 964 00:45:46,725 --> 00:45:48,293 YEARS SINCE THERE'S BEEN FAST 965 00:45:48,293 --> 00:45:49,895 ACCUMULATING EVIDENCE THAT 966 00:45:49,895 --> 00:45:54,199 INDEED THE PREVALENCE OF 967 00:45:54,199 --> 00:45:55,901 PRECANCEROUS LESIONS AND CANCER 968 00:45:55,901 --> 00:45:59,771 IS THE SAME IN PEOPLE IN THEIR 969 00:45:59,771 --> 00:46:03,442 LATE 40s AS THOSE IN THEIR EARLY 970 00:46:03,442 --> 00:46:04,743 50s. 971 00:46:04,743 --> 00:46:07,646 THESE ARE TWO OF THE EARLIER 972 00:46:07,646 --> 00:46:08,213 STUDIES THAT REPORTED THIS 973 00:46:08,213 --> 00:46:11,516 FINDING. 974 00:46:11,516 --> 00:46:13,518 AND THEN THIS IS THE MOST RECENT 975 00:46:13,518 --> 00:46:13,718 PAPER. 976 00:46:13,718 --> 00:46:21,159 THIS IS A STUDY OF KAISER B 977 00:46:21,159 --> 00:46:23,995 BENEFICIARIES WHO TESTED 978 00:46:23,995 --> 00:46:26,131 POSITIVE ON THE STOOL TEST, THE 979 00:46:26,131 --> 00:46:27,499 FIT TEST. 980 00:46:27,499 --> 00:46:32,537 THIS WAS LOOKING AT PEOPLE 35 TO 981 00:46:32,537 --> 00:46:34,773 49 THE NEWLY ELIGIBLE SCREENING 982 00:46:34,773 --> 00:46:37,642 GROUP COMPARED TO PEOPLE WHO ARE 983 00:46:37,642 --> 00:46:40,745 50 AND THIS IS COLONOSCOPY 984 00:46:40,745 --> 00:46:43,048 FOLLOW-UP OF A POSITIVE STOOL 985 00:46:43,048 --> 00:46:43,248 TEST. 986 00:46:43,248 --> 00:46:46,818 THEY FOUND INDEED REGARDLESS OF 987 00:46:46,818 --> 00:46:48,420 AGE, THERE WAS THE SAME 988 00:46:48,420 --> 00:46:51,723 PREVALENCE OF ADVANCED ADENOMA 989 00:46:51,723 --> 00:46:55,127 AND SERRATED LESIONS AND CANCER. 990 00:46:55,127 --> 00:46:59,364 ALL THIS REALLY SUPPORTS THE USE 991 00:46:59,364 --> 00:47:01,066 OF SCREENING TO DAMPEN THE 992 00:47:01,066 --> 00:47:04,469 DISEASE BURDEN. 993 00:47:04,469 --> 00:47:15,013 SO, WHERE ARE WE WITH SCREENING? 994 00:47:19,384 --> 00:47:22,187 THESE ARE RECOMMENDED TESTS. 995 00:47:22,187 --> 00:47:24,990 STOOL TESTING AND CT COLONOSCOPY 996 00:47:24,990 --> 00:47:26,024 AND THIS IS ANY RECOMMENDED 997 00:47:26,024 --> 00:47:29,461 TEST. 998 00:47:29,461 --> 00:47:35,267 IT WAS VERY EXCITING TO SEE THE 999 00:47:35,267 --> 00:47:37,702 INCREASE IN THE NEWLY ELIGIBLE 1000 00:47:37,702 --> 00:47:41,206 AGE GROUP 20% IN 2023 BUT STILL 1001 00:47:41,206 --> 00:47:42,674 FAR BELOW WHERE WE ARE WITH 1002 00:47:42,674 --> 00:47:49,181 PEOPLE 65 AND OLDER. 1003 00:47:49,181 --> 00:47:49,748 80% OF WHOM ARE CURRENT FOR 1004 00:47:49,748 --> 00:47:57,289 SCREENING. 1005 00:47:57,289 --> 00:48:00,458 I WANTED TO END ON A POSITIVE 1006 00:48:00,458 --> 00:48:01,259 NOTE. 1007 00:48:01,259 --> 00:48:02,561 THESE PAPERS ARE FROM A PAPER IN 1008 00:48:02,561 --> 00:48:04,162 PRESS RIGHT NOW. 1009 00:48:04,162 --> 00:48:07,666 AND THIS IS THAT WE'RE SEEING 1010 00:48:07,666 --> 00:48:10,735 EARLY SIGNS OF SCREENING UPTAKE 1011 00:48:10,735 --> 00:48:14,539 IN THE 45 TO 49 YEAR AGE GROUP. 1012 00:48:14,539 --> 00:48:17,809 THESE ARE INCIDENT RATES JUST 1013 00:48:17,809 --> 00:48:21,880 FROM 1998 TO 2021 OVER ALL ON 1014 00:48:21,880 --> 00:48:24,349 THE FAR LEFT AND FOR LOCALIZED 1015 00:48:24,349 --> 00:48:26,084 STAGE IN THE MIDDLE AND ADVANCED 1016 00:48:26,084 --> 00:48:32,624 STAGE DISEASE ON THE RIGHT. 1017 00:48:32,624 --> 00:48:34,059 FOR LOCALIZED STAGE DISEASE 1018 00:48:34,059 --> 00:48:36,161 THERE WAS A 7% INCREASE FROM 1019 00:48:36,161 --> 00:48:39,798 2018 TO 2021. 1020 00:48:39,798 --> 00:48:45,670 AND THIS FOLLOWS OF A STIFT 1021 00:48:45,670 --> 00:48:47,872 WHICH I SIGNIFICANT DECLINE IN 1022 00:48:47,872 --> 00:48:50,609 THE PREVIOUS DECADE OF 1.6% PER 1023 00:48:50,609 --> 00:48:51,176 YEAR. 1024 00:48:51,176 --> 00:48:55,480 THIS IS A STRONG SIGN THIS IS 1025 00:48:55,480 --> 00:48:57,716 THE DIAGNOSIS OF ASYMPTOMATIC 1026 00:48:57,716 --> 00:48:59,517 CANCERS BECAUSE OF THE UPTAKE OF 1027 00:48:59,517 --> 00:49:00,518 SCREENING. 1028 00:49:00,518 --> 00:49:03,321 BECAUSE AS I SAID EARLIER, 1029 00:49:03,321 --> 00:49:06,224 LOCALIZED STAGE DISEASE USUALLY 1030 00:49:06,224 --> 00:49:09,194 DOES NOT HAVE SYMPTOMS. 1031 00:49:09,194 --> 00:49:10,695 BUT IMPORTANT TO REALIZE THERE'S 1032 00:49:10,695 --> 00:49:14,699 STILL A VERY STEADY AND STEEP 1033 00:49:14,699 --> 00:49:16,768 INCREASE IN ADVANCED STAGE 1034 00:49:16,768 --> 00:49:21,573 DISEASE WHICH IS REGIONAL AND 1035 00:49:21,573 --> 00:49:22,173 COMBINED. 1036 00:49:22,173 --> 00:49:24,109 WE'RE HOPEFUL WITH MORE 1037 00:49:24,109 --> 00:49:25,243 SCREENING WE'LL BE ABLE TO 1038 00:49:25,243 --> 00:49:31,583 DAMPEN THIS TREND. 1039 00:49:31,583 --> 00:49:35,086 SO IN SUMMARY COLORECTAL CANCER 1040 00:49:35,086 --> 00:49:37,989 RATES ARE INCREASING IN PEOPLE 1041 00:49:37,989 --> 00:49:42,294 BORNE AFTER CIRCA 1950 WITH THE 1042 00:49:42,294 --> 00:49:43,595 BUR 1043 00:49:43,595 --> 00:49:46,631 BURDEN SHIFTING TO YOUNGER 1044 00:49:46,631 --> 00:49:48,867 PEOPLE IN THE RECTUM AND DISTAL 1045 00:49:48,867 --> 00:49:50,502 COLON AND ADVANCED STAGE 1046 00:49:50,502 --> 00:49:50,735 DISEASE. 1047 00:49:50,735 --> 00:49:52,270 I HOPE I'VE CONVINCED EVERYONE 1048 00:49:52,270 --> 00:49:53,138 THIS IS NOT AN EARLY ONSET 1049 00:49:53,138 --> 00:49:56,708 PROBLEM. 1050 00:49:56,708 --> 00:50:00,879 THIS IS A GLOBAL PROBLEM THAT 1051 00:50:00,879 --> 00:50:01,513 NEEDS TO BE UNDERSTOOD AND 1052 00:50:01,513 --> 00:50:06,751 ADDRESSED. 1053 00:50:06,751 --> 00:50:09,187 THIS INCREASE IS HAPPENING 1054 00:50:09,187 --> 00:50:11,623 INCREASINGLY ON A GLOBAL SCALE 1055 00:50:11,623 --> 00:50:12,390 IN MANY HIGH INCOME COUNTRIES 1056 00:50:12,390 --> 00:50:17,429 AROUND THE WORLD. 1057 00:50:17,429 --> 00:50:19,064 AND ESTABLISHED RISK FACTORS 1058 00:50:19,064 --> 00:50:21,633 DON'T APPEAR TO BE THE SOLE 1059 00:50:21,633 --> 00:50:25,503 CAUSE THOUGH CERTAINLY EXCESS 1060 00:50:25,503 --> 00:50:27,539 BODY WEIGHT AND OUR MORE 1061 00:50:27,539 --> 00:50:28,173 SEDENTARY LIFESTYLE ARE 1062 00:50:28,173 --> 00:50:29,441 CONTRIBUTING IN SOME WAY TO THE 1063 00:50:29,441 --> 00:50:29,708 INCREASE. 1064 00:50:29,708 --> 00:50:32,944 SO WHAT CAN WE DO NOW TO HELP 1065 00:50:32,944 --> 00:50:34,913 MITIGATE THIS GROWING BURDEN? 1066 00:50:34,913 --> 00:50:36,748 I DO THINK THERE'S A LOT THAT 1067 00:50:36,748 --> 00:50:38,383 CAN BE DONE. 1068 00:50:38,383 --> 00:50:39,317 ONE IS SCREENING. 1069 00:50:39,317 --> 00:50:41,119 WE'VE ALREADY TALKED ABOUT THAT. 1070 00:50:41,119 --> 00:50:43,254 IT CAN REALLY MAKE A DIFFERENCE 1071 00:50:43,254 --> 00:50:45,857 AND I WOULD POINT TO THE VERY 1072 00:50:45,857 --> 00:50:48,193 FIRST SLIDE I SHOWED. 1073 00:50:48,193 --> 00:50:52,097 WE SAW ACCELERATED DECREASES IN 1074 00:50:52,097 --> 00:50:55,700 BOTH INCIDENTS AND MORTALITY 1075 00:50:55,700 --> 00:50:58,203 WHEN THERE WAS WIDESPREAD 1076 00:50:58,203 --> 00:50:58,970 COLONOSCOPY UPTAKE IN THE 1077 00:50:58,970 --> 00:51:01,005 U.S. OVER ALL SO WE KNOW IT CAN 1078 00:51:01,005 --> 00:51:03,141 BE EFFECTIVE. 1079 00:51:03,141 --> 00:51:05,310 THERE ARE MANY PEOPLE DIAGNOSED 1080 00:51:05,310 --> 00:51:05,744 BEFORE 45. 1081 00:51:05,744 --> 00:51:08,179 SO INCREASING THE AWARENESS OF 1082 00:51:08,179 --> 00:51:11,116 SYMPTOMS AND JUST THE FACT THAT 1083 00:51:11,116 --> 00:51:13,051 DISEASE INCREASE IS INCREASING 1084 00:51:13,051 --> 00:51:16,488 IN YOUNGER ADULTS. 1085 00:51:16,488 --> 00:51:19,257 RECTAL BLEEDING AND ABDOMINAL 1086 00:51:19,257 --> 00:51:20,258 PAIN ARE THE TWO MOST COMMON 1087 00:51:20,258 --> 00:51:21,793 SYMPTOMS IN YOUNG ADULTS AND 1088 00:51:21,793 --> 00:51:23,828 THIS IS DIFFERENT THAN OLDER 1089 00:51:23,828 --> 00:51:26,398 PATIENTS BECAUSE THESE ARE 1090 00:51:26,398 --> 00:51:29,167 PREDOMINANTLY RECTAL CANCERS. 1091 00:51:29,167 --> 00:51:31,503 THIS IS THE SYMPTOMOLOGY. 1092 00:51:31,503 --> 00:51:35,607 AND BE THE ALSO REDUCING THE 1093 00:51:35,607 --> 00:51:38,176 STIGMA BECAUSE THAT DELAY IN 1094 00:51:38,176 --> 00:51:40,412 PATIENT FOLLOW-UP AT THE CLINIC 1095 00:51:40,412 --> 00:51:44,382 WITH THEIR SYMPTOMS IS OFTEN 1096 00:51:44,382 --> 00:51:46,251 TIMES BECAUSE OF EMBARRASSMENT. 1097 00:51:46,251 --> 00:51:49,354 SO REDUCING STIGMA OF THIS 1098 00:51:49,354 --> 00:51:49,988 DISEASE AND THE SYMPTOMS AROUND 1099 00:51:49,988 --> 00:51:52,690 IT. 1100 00:51:52,690 --> 00:51:56,594 I'D LIKE TO GIVE A BIG BIG THANK 1101 00:51:56,594 --> 00:51:59,230 YOU TO CANCER REGISTRARS IN THE 1102 00:51:59,230 --> 00:52:01,766 U.S. AND GLOBALLY THAT ALLOW US 1103 00:52:01,766 --> 00:52:04,436 TO DO ALL OF THIS WORK AS WELL 1104 00:52:04,436 --> 00:52:07,105 AS MY ACS COLLABORATORS. 1105 00:52:07,105 --> 00:52:10,108 I THANK YOU SO MUCH FOR YOUR 1106 00:52:10,108 --> 00:52:20,285 ATTENTION. 1107 00:52:46,277 --> 00:52:48,947 >> THERE'S BEEN A FOCUS ON 1108 00:52:48,947 --> 00:52:53,485 GENETIC AND MOLECULAR ASPECTS OF 1109 00:52:53,485 --> 00:52:54,686 COLORECTAL CANCER IN THE 1110 00:52:54,686 --> 00:53:04,162 INHERITABLE AND SPORADIC FORMS. 1111 00:53:04,162 --> 00:53:04,762 SANDY, WOULD YOU PLEASE CARRY 1112 00:53:04,762 --> 00:53:07,532 ON. 1113 00:53:07,532 --> 00:53:14,706 >> WIN, AM I VISIBLE? 1114 00:53:14,706 --> 00:53:16,508 >> YOUR BACKGROUND SCREEN IS 1115 00:53:16,508 --> 00:53:17,075 VISIBLE. 1116 00:53:17,075 --> 00:53:18,409 YOU'RE NOT IN THAT ROOM ON THE 1117 00:53:18,409 --> 00:53:21,379 BEACH. 1118 00:53:21,379 --> 00:53:23,848 BUT MAYBE YOU CAN START SHARING. 1119 00:53:23,848 --> 00:53:26,351 >> LET'S SEE IF I CAN FIGURE OUT 1120 00:53:26,351 --> 00:53:31,556 HOW TO GET MYSELF VISIBLE. 1121 00:53:31,556 --> 00:53:33,358 >> OKAY. 1122 00:53:33,358 --> 00:53:35,093 THERE YOU ARE. 1123 00:53:35,093 --> 00:53:36,594 >> AND YOU CAN HEAR ME? 1124 00:53:36,594 --> 00:53:47,005 >> YES, WE CAN HEAR YOU. 1125 00:54:04,289 --> 00:54:07,759 AND YOU'RE PROBABLY SEEING NOW 1126 00:54:07,759 --> 00:54:09,561 THE MAC PRESENTER MODE. 1127 00:54:09,561 --> 00:54:13,831 >> NOT QUITE. 1128 00:54:13,831 --> 00:54:14,198 THERE IT IS. 1129 00:54:14,198 --> 00:54:18,736 >> OKAY. 1130 00:54:18,736 --> 00:54:22,807 WELL, WIN, THANKS VERY MUCH FOR 1131 00:54:22,807 --> 00:54:29,213 INVITING ME TO PRESENT IN THIS 1132 00:54:29,213 --> 00:54:30,381 CERTAINLY DISTINGUISHED SEMINAR 1133 00:54:30,381 --> 00:54:38,556 SERIES WITH A GREAT LEGACY. 1134 00:54:38,556 --> 00:54:40,758 REBECCA JUST TALKED ABOUT THE 1135 00:54:40,758 --> 00:54:42,560 EPIDEMIOLOGY OF THE ONSET OF 1136 00:54:42,560 --> 00:54:46,230 YOUNG COLORECTAL CANCER AND I 1137 00:54:46,230 --> 00:54:48,199 CAN PROVIDE THE MOLECULAR 1138 00:54:48,199 --> 00:54:50,602 EXPLANATION FOR THE OBSERVATION 1139 00:54:50,602 --> 00:54:52,103 BUT NO BODY HAS ONE. 1140 00:54:52,103 --> 00:54:54,572 WHAT I'M GOING TO DO IS TALK 1141 00:54:54,572 --> 00:54:56,040 ABOUT WHAT'S BEEN LEARNED FROM 1142 00:54:56,040 --> 00:54:59,477 THE STUDY OF YOUNG ONSET CO 1143 00:54:59,477 --> 00:55:03,915 COLORECTAL CANCER IN FAMILIES IN 1144 00:55:03,915 --> 00:55:05,583 THE HOPE IT PROVIDES OPTIMISM 1145 00:55:05,583 --> 00:55:08,286 THE PROBLEMS ARE SOLVABLE AND 1146 00:55:08,286 --> 00:55:10,455 ALSO REASON TO CONTINUE ON 1147 00:55:10,455 --> 00:55:12,223 BECAUSE IT TURNS OUT ANSWERING 1148 00:55:12,223 --> 00:55:15,560 THESE TYPES OF QUESTIONS TURNED 1149 00:55:15,560 --> 00:55:20,231 OUT TO HAVE BROAD IMPACT BEYOND 1150 00:55:20,231 --> 00:55:23,267 JUST IS THE INITIAL POPULATION 1151 00:55:23,267 --> 00:55:25,970 THAT'S BEING THE OBJECT OF 1152 00:55:25,970 --> 00:55:26,170 STUDY. 1153 00:55:26,170 --> 00:55:27,872 I'M GOING TO TALK ABOUT STUDIES 1154 00:55:27,872 --> 00:55:32,577 THAT WERE DONE IN YOUNG ONSET 1155 00:55:32,577 --> 00:55:34,178 HEREDITARY COLORECTAL CANCER 1156 00:55:34,178 --> 00:55:36,814 GOING BACK NOW 20 SOMETHING 1157 00:55:36,814 --> 00:55:40,184 YEARS BETWEEN OUR GROUP AND 1158 00:55:40,184 --> 00:55:42,186 COLLABORATORS. 1159 00:55:42,186 --> 00:55:43,988 THESE ARE MY DISCLOSURES. 1160 00:55:43,988 --> 00:55:49,594 I WILL BE TALKING ABOUT 1161 00:55:49,594 --> 00:55:50,328 HETEROLO 1162 00:55:50,328 --> 00:55:53,931 HETEROLOGIES AND INTERESTS. 1163 00:55:53,931 --> 00:55:55,733 LET'S TALK A LITTLE BIT ABOUT 1164 00:55:55,733 --> 00:55:57,402 COLORECTAL CANCER FOR A MOMENT. 1165 00:55:57,402 --> 00:55:59,637 IT HAS PROGRESSIVE CLINICAL 1166 00:55:59,637 --> 00:55:59,904 STAGES. 1167 00:55:59,904 --> 00:56:02,407 THE FIRST STAGE IS SHOWN ON THE 1168 00:56:02,407 --> 00:56:04,642 LEFT IS NOT CANCER AT ALL. 1169 00:56:04,642 --> 00:56:08,212 IT'S A BENIGN PRECURSOR FOR THE 1170 00:56:08,212 --> 00:56:09,447 COLORECTAL CANCER IN THE FORM OF 1171 00:56:09,447 --> 00:56:11,849 A TUBULAR ADENOMA AND YOU SEE IT 1172 00:56:11,849 --> 00:56:15,586 AS A BUMP IN THE WALL OF THE 1173 00:56:15,586 --> 00:56:21,793 COLON IN THIS EXAMINATION AND 1174 00:56:21,793 --> 00:56:23,861 OVERTIME THESE BENIGN TUMORS CAN 1175 00:56:23,861 --> 00:56:27,899 PROGRESS AND BECOME INVASIVE 1176 00:56:27,899 --> 00:56:30,034 COLORECTAL CANCERS AS YOU SEE 1177 00:56:30,034 --> 00:56:35,139 HERE WHERE THE COLON'S BEEN OPEN 1178 00:56:35,139 --> 00:56:37,508 TO EXPOSE THE TUMOR ON THE 1179 00:56:37,508 --> 00:56:37,742 INSIDE. 1180 00:56:37,742 --> 00:56:39,977 WITH TIME THEY CAN SPREAD BEYOND 1181 00:56:39,977 --> 00:56:43,314 THE WALL OF THE COLON. 1182 00:56:43,314 --> 00:56:44,182 MOST CHARACTERISTICALLY SPREAD 1183 00:56:44,182 --> 00:56:45,717 TO THE LIVER AND METASTATIC 1184 00:56:45,717 --> 00:56:48,686 DISEASE WHICH IS LARGELY 1185 00:56:48,686 --> 00:56:48,986 INCURRABLE. 1186 00:56:48,986 --> 00:56:53,825 HERE YOU SEE A PICTURE OF COLON 1187 00:56:53,825 --> 00:56:54,525 CANCER AND PATIENTS EXPOSED IN 1188 00:56:54,525 --> 00:57:00,598 THE OPERATING ROOM. 1189 00:57:00,598 --> 00:57:04,168 NOW, THROUGH THE EFFORTS OF MANY 1190 00:57:04,168 --> 00:57:06,003 LABORATORIES AND PREDOMINANTLY A 1191 00:57:06,003 --> 00:57:07,772 LOT OF HAS BEEN LEARNED ABOUT 1192 00:57:07,772 --> 00:57:09,273 THE GENES THAT DRIVE THE 1193 00:57:09,273 --> 00:57:10,608 DEVELOPMENT OF COLORECTAL 1194 00:57:10,608 --> 00:57:11,542 CANCER. 1195 00:57:11,542 --> 00:57:14,412 THIS IS A FIGURE FROM A REVIEW 1196 00:57:14,412 --> 00:57:17,281 IN THE NEW ENGLAND JOURNAL OF 1197 00:57:17,281 --> 00:57:18,182 MEDICINE SEVERAL YEARS AGO. 1198 00:57:18,182 --> 00:57:22,053 AND ON THE TOP YOU SEE GENES 1199 00:57:22,053 --> 00:57:25,123 THAT ARE INVOLVED IN THESE 1200 00:57:25,123 --> 00:57:29,060 PROGRESSIVE STAGES OF COLORECTAL 1201 00:57:29,060 --> 00:57:29,761 CANCER. 1202 00:57:29,761 --> 00:57:34,632 THE GENES DRIVES THE DEVELOPMENT 1203 00:57:34,632 --> 00:57:40,538 OF COLORECTAL CANCER AND THESE 1204 00:57:40,538 --> 00:57:44,709 ARE GENES THAT ARE ACTIVATED AND 1205 00:57:44,709 --> 00:57:48,579 SOME ARE DEACTIVATED AN YOU SEE 1206 00:57:48,579 --> 00:57:54,986 GRAY FACTOR PATHWAYS THE COX 2 1207 00:57:54,986 --> 00:58:05,463 THE TARGET OF NON STEROIDAL 1208 00:58:06,998 --> 00:58:09,734 INFLAMMATORY DRUGS AND OPPOSING 1209 00:58:09,734 --> 00:58:11,769 FACTORS SUCH AS GROWTH FACTOR 1210 00:58:11,769 --> 00:58:12,136 DATA. 1211 00:58:12,136 --> 00:58:15,807 WHAT I'M GOING TO TELL YOU IS 1212 00:58:15,807 --> 00:58:17,608 STUDIES FROM OUR LAB THAT PUT 1213 00:58:17,608 --> 00:58:18,276 SEVERAL OF THE GENES AND 1214 00:58:18,276 --> 00:58:23,381 PATHWAYS DEPICTED ON THE MAP 1215 00:58:23,381 --> 00:58:25,349 INTO OUR UNDERSTANDING OF 1216 00:58:25,349 --> 00:58:26,450 COLORECTAL CANCER. 1217 00:58:26,450 --> 00:58:28,486 AND THESE STUDIES COMMENCED 1218 00:58:28,486 --> 00:58:31,522 THROUGH OUR STUDIES OF 1219 00:58:31,522 --> 00:58:38,196 HEREDITARY COLON CANCER OR AS IS 1220 00:58:38,196 --> 00:58:41,833 OFTEN KNOWN AND WHAT YOU SEE IS 1221 00:58:41,833 --> 00:58:45,369 THE FAMILY SLIDE OF A PATIENT 1222 00:58:45,369 --> 00:58:47,505 TWO AND A HALF DECADES AGO. 1223 00:58:47,505 --> 00:58:50,141 HE WAS A 33-YEAR-OLD ACCOUNTANT 1224 00:58:50,141 --> 00:58:56,714 FROM A CLEVELAND SUBURB AND HAD 1225 00:58:56,714 --> 00:59:04,689 COLORECTEL CANCER AND EVEN MORE 1226 00:59:04,689 --> 00:59:08,726 AND WHAT IS MORE SURPRISING IS 1227 00:59:08,726 --> 00:59:12,463 THE FAMILY HISTORY SIMILAR ONSET 1228 00:59:12,463 --> 00:59:15,399 COLORECTAL CANCER KILLED HIS 1229 00:59:15,399 --> 00:59:17,869 FATHER AND GRANDFATHER. 1230 00:59:17,869 --> 00:59:19,136 MOREOVER, WHEN WE INQUIRED ABOUT 1231 00:59:19,136 --> 00:59:21,772 OTHER MEMBERS OF THE FAMILY, WE 1232 00:59:21,772 --> 00:59:24,141 FOUND THERE WERE YOUNG ONSET 1233 00:59:24,141 --> 00:59:25,610 ENDOMETRIAL AND OVARIAN CANCERS 1234 00:59:25,610 --> 00:59:26,410 IN FEMALE MEMBERS OF THIS 1235 00:59:26,410 --> 00:59:30,181 KINDRED. 1236 00:59:30,181 --> 00:59:33,951 NOW, TODAY THIS IS RECOGNIZED AS 1237 00:59:33,951 --> 00:59:34,452 PROTOTYPICAL SYNDROME. 1238 00:59:34,452 --> 00:59:38,723 AT THE TIME I FIRST SAW THE 1239 00:59:38,723 --> 00:59:45,529 INDIVIDUAL THE SYNDROME WASN'T 1240 00:59:45,529 --> 00:59:49,734 YET IN THE MEDICAL TEXTBOOKS AND 1241 00:59:49,734 --> 00:59:51,669 SKEPTICALLY VIEWED AS BAD LUCK 1242 00:59:51,669 --> 00:59:53,504 THE COOCCURRENCE OF COMMON 1243 00:59:53,504 --> 00:59:54,605 CANCERS BUT IF YOU LOOKED HARD 1244 00:59:54,605 --> 01:00:00,244 ENOUGH YOU WOULD FIND. 1245 01:00:00,244 --> 01:00:04,615 WE RECOGNIZE THIS AS POTENTIALLY 1246 01:00:04,615 --> 01:00:06,851 REPRESENTING A NEW GENETIC 1247 01:00:06,851 --> 01:00:09,353 SYNDROME AND SO WE HARVESTED THE 1248 01:00:09,353 --> 01:00:10,588 PATIENT'S TUMOR AFTER HIS DEMISE 1249 01:00:10,588 --> 01:00:18,529 AND SUCCEEDED IN GROWING THAT 1250 01:00:18,529 --> 01:00:19,931 POSTHUMOUS SAMPLE IN THE 1251 01:00:19,931 --> 01:00:21,032 LABORATORY AND THEN TURNED TO 1252 01:00:21,032 --> 01:00:22,633 OTHER PATIENTS WE WERE ABLE TO 1253 01:00:22,633 --> 01:00:26,170 IDENTIFY WITH SIMILAR HISTORIES 1254 01:00:26,170 --> 01:00:29,907 AND ULTIMATELY WERE ABLE TO 1255 01:00:29,907 --> 01:00:30,942 ESTABLISH A SMALL PANEL OF CELL 1256 01:00:30,942 --> 01:00:33,945 LINES WE CONTRIBUTED TO THE 1257 01:00:33,945 --> 01:00:38,382 EFFORTS FOCUSSED ON GENETIC 1258 01:00:38,382 --> 01:00:42,353 INTERROGATION OF THE SYNDROME 1259 01:00:42,353 --> 01:00:43,821 AND NO EFFORTS LED TO THE 1260 01:00:43,821 --> 01:00:44,956 IDENTIFICATION THAT OUR PATIENT 1261 01:00:44,956 --> 01:00:46,958 AND OTHER PATIENTS CONTRIBUTED 1262 01:00:46,958 --> 01:00:50,728 TO THE STUDY ALL HAD IN BORN 1263 01:00:50,728 --> 01:00:52,897 ERRORS IN A SYSTEM KNOWN AS 1264 01:00:52,897 --> 01:00:56,634 SYSTEM DNA MISMATCH REPAIR. 1265 01:00:56,634 --> 01:00:59,136 THAT COULD BE SIMPLY THOUGHT OF 1266 01:00:59,136 --> 01:01:01,572 AS A DNA SPELL CHECKER. 1267 01:01:01,572 --> 01:01:03,774 IT'S A PROTEIN COMPLEX OF FOUR 1268 01:01:03,774 --> 01:01:07,478 DIFFERENT SUB UNITS AND IT RUNS 1269 01:01:07,478 --> 01:01:14,018 ALONG THE DOUBLE HELIX 1270 01:01:14,018 --> 01:01:18,289 REPLICATION AND THOSE CREATE A 1271 01:01:18,289 --> 01:01:21,292 SMALL BUBBLE IN THE DOUBLE HELIX 1272 01:01:21,292 --> 01:01:24,462 WHERE YOU DON'T HAVE 1273 01:01:24,462 --> 01:01:34,171 COMPLEMEN 1274 01:01:34,171 --> 01:01:36,640 COMPLEMENTARY BASIS IS OPPOSITE 1275 01:01:36,640 --> 01:01:39,010 ONE ANOTHER AND THE PATIENT HAD 1276 01:01:39,010 --> 01:01:41,412 BEEN BORN WITH INACTIVATION OF 1277 01:01:41,412 --> 01:01:48,252 THE MH2 SUB UNIT OF THE CHECKER 1278 01:01:48,252 --> 01:01:53,657 AND MOST PATIENTS HAD A SUB UNIT 1279 01:01:53,657 --> 01:01:58,229 OF THE SPELL CHECKER AND THIS 1280 01:01:58,229 --> 01:02:01,332 WAS A SYNDROME NOT JUST BAD LUCK 1281 01:02:01,332 --> 01:02:05,236 BUT DUE TO FORTUNATE MISCUES. 1282 01:02:05,236 --> 01:02:09,173 AND THE MOMENT THIS DISCOVERY 1283 01:02:09,173 --> 01:02:11,308 WAS MADE WAS WHAT WOULD THE 1284 01:02:11,308 --> 01:02:13,744 CONNECTION BE BETWEEN HAVING A 1285 01:02:13,744 --> 01:02:17,148 MUTATION THAT INACTIVATED THE 1286 01:02:17,148 --> 01:02:19,650 MISMATCH REPAIR DNA SYSTEM SPELL 1287 01:02:19,650 --> 01:02:23,587 CHECKER AND THE COLORECTAL 1288 01:02:23,587 --> 01:02:23,821 CANCER? 1289 01:02:23,821 --> 01:02:25,156 OUR TEAM HYPOTHESIZED THERE MUST 1290 01:02:25,156 --> 01:02:28,926 BE A GENE CRUCIAL TO THE 1291 01:02:28,926 --> 01:02:31,562 PREVENTION OF COLORECTAL CANCER 1292 01:02:31,562 --> 01:02:33,631 AND HAD SOME SORT OF STRUCTURE 1293 01:02:33,631 --> 01:02:35,366 IT WAS CRUCIALLY DEPENDENT ON 1294 01:02:35,366 --> 01:02:38,669 THE DNA MISMATCH REPAIR SYSTEM 1295 01:02:38,669 --> 01:02:41,072 TO MAINTAIN ITS GENOMIC 1296 01:02:41,072 --> 01:02:43,507 INTEGRITY AND WE SUCCEEDED IN 1297 01:02:43,507 --> 01:02:44,942 IDENTIFYING SUCH A GENE AND IT 1298 01:02:44,942 --> 01:02:51,916 WAS THE TYPE 2 RECEPTOR FOR THE 1299 01:02:51,916 --> 01:02:54,685 TGF BETA AND THE TGF BETA TYPE 2 1300 01:02:54,685 --> 01:02:58,622 RECEPTORS ARE A SIMPLE TYPE 1 1301 01:02:58,622 --> 01:03:01,125 PROTEIN AND INTERMINUS OUTSIDE 1302 01:03:01,125 --> 01:03:03,427 THE CELL AND C TERMINUS INSIDE 1303 01:03:03,427 --> 01:03:03,828 THE CELL. 1304 01:03:03,828 --> 01:03:06,697 WHAT WE NOTED WAS THERE WAS A 1305 01:03:06,697 --> 01:03:07,465 VERY UNUSUAL SEQUENCE IN THE 1306 01:03:07,465 --> 01:03:10,601 GENE ENCODING THIS RECEPTOR 1307 01:03:10,601 --> 01:03:16,240 WHICH WAS 10 REPEATS OF THE SAME 1308 01:03:16,240 --> 01:03:18,109 DNA BASE ALL IN A ROW. 1309 01:03:18,109 --> 01:03:19,944 AS YOU WOULD IMAGINE IF YOU 1310 01:03:19,944 --> 01:03:24,682 TRIED TO SAY AAAAAAAA AND STOP 1311 01:03:24,682 --> 01:03:30,187 EXACTLY ON THE 10th A YOU MAY 1312 01:03:30,187 --> 01:03:34,058 STUTTER AND THE POLYMERASE HAS 1313 01:03:34,058 --> 01:03:34,792 THE SAME PROBLEM. 1314 01:03:34,792 --> 01:03:38,229 THERE'S ENORMOUS RELIANCE ON THE 1315 01:03:38,229 --> 01:03:42,133 DNA SPELL CHECKER TO CORRECT THE 1316 01:03:42,133 --> 01:03:43,934 STUTTERING ACROSS THE RUN THE 1317 01:03:43,934 --> 01:03:46,737 DNA POLYMERASE HAS TROUBLE 1318 01:03:46,737 --> 01:03:47,705 FAITHFULLY COPYING. 1319 01:03:47,705 --> 01:03:49,206 SUCH AS WHEN WE LOOKED AT ALL 1320 01:03:49,206 --> 01:03:51,308 THE COLON CANCERS THAT AROSE IN 1321 01:03:51,308 --> 01:03:54,145 PATIENTS WITH THE SYNDROME, WE 1322 01:03:54,145 --> 01:03:55,846 FOUND THIS GENE HAD BEEN 1323 01:03:55,846 --> 01:03:58,582 INACTIVATED IN 100% OF THE 1324 01:03:58,582 --> 01:04:01,385 TUMORS AND THE INACTIVATIONS 1325 01:04:01,385 --> 01:04:03,854 WERE STUTTERING OF THE DNA 1326 01:04:03,854 --> 01:04:05,823 POLYMERASE THAT ADDED OR 1327 01:04:05,823 --> 01:04:07,391 SUBTRACTED AN A OR TWO As FROM 1328 01:04:07,391 --> 01:04:10,127 THE GENE WHEN IT WAS COPIED. 1329 01:04:10,127 --> 01:04:12,129 ALL THESE STUTTERING ERRORS HAVE 1330 01:04:12,129 --> 01:04:13,631 THE SAME EFFECT. 1331 01:04:13,631 --> 01:04:15,599 THEY CREATED A STOP MUTATION IN 1332 01:04:15,599 --> 01:04:17,801 THE GENE AND CREATED A PROTEIN 1333 01:04:17,801 --> 01:04:20,971 THAT WAS NOW TRUNCATED AND NO 1334 01:04:20,971 --> 01:04:22,306 LONGER ACROSS THE CELL MEMBRANE 1335 01:04:22,306 --> 01:04:23,207 AS THEY WERE ABLE TO SIGNAL INTO 1336 01:04:23,207 --> 01:04:27,411 THE CELL. 1337 01:04:27,411 --> 01:04:31,282 WHAT IS IT TGF BETA DOES AND WHY 1338 01:04:31,282 --> 01:04:33,617 WOULD THE BETA RECEPTOR MATTER? 1339 01:04:33,617 --> 01:04:35,719 THIS IS WHAT THE HISTOLOGY OF 1340 01:04:35,719 --> 01:04:37,188 THE COLON LOOKS LIKE. 1341 01:04:37,188 --> 01:04:40,624 HERE YOU HAVE THE BANDS OF 1342 01:04:40,624 --> 01:04:42,193 MUSCLE THAT SQUEEZED OR ENABLE 1343 01:04:42,193 --> 01:04:44,728 THE COLON TO CONTRACT AND REPEL 1344 01:04:44,728 --> 01:04:46,263 THE DIGESTIVE CONTENTS THROUGH 1345 01:04:46,263 --> 01:04:50,000 THE GUT. 1346 01:04:50,000 --> 01:04:55,973 AND UP HERE SEE THE EPITHELIAL 1347 01:04:55,973 --> 01:04:58,042 CELLS THE COLUMNS OF CELLS AND 1348 01:04:58,042 --> 01:05:00,444 THIS IS THE INNER LINING OF THE 1349 01:05:00,444 --> 01:05:04,915 COLON, THE FECAL STREAM IS UP 1350 01:05:04,915 --> 01:05:07,885 HERE ABOVE THESE EPITHELIAL 1351 01:05:07,885 --> 01:05:10,688 LINING AND THIS EPITHELIA IS 1352 01:05:10,688 --> 01:05:12,156 AMONG THE FASTEST 1353 01:05:12,156 --> 01:05:14,792 PROLIFERATING -- AND THE ENTIRE 1354 01:05:14,792 --> 01:05:17,294 TISSUE REMOVES ITSELF ON A 1355 01:05:17,294 --> 01:05:17,962 WEEKLY BASIS. 1356 01:05:17,962 --> 01:05:20,364 SO WHAT HAPPENS IS NEW CELLS ARE 1357 01:05:20,364 --> 01:05:22,766 GENERATED AT THE BASE OF THE 1358 01:05:22,766 --> 01:05:23,968 COLUMNS AND THEN MATURE CELLS 1359 01:05:23,968 --> 01:05:29,673 DIE AND SLOUGHED OFF INTO THE 1360 01:05:29,673 --> 01:05:32,610 LUMEN -- AND IT PLAYS A CRUCIAL 1361 01:05:32,610 --> 01:05:34,945 ROLE IN THE CONTROL THAT LEADS 1362 01:05:34,945 --> 01:05:36,747 TO THE MATURATION AND DEATH OF 1363 01:05:36,747 --> 01:05:39,283 THE CELLS AFTER A FEW DAYS' 1364 01:05:39,283 --> 01:05:40,050 TIME. 1365 01:05:40,050 --> 01:05:43,254 SO HERE WE HAVE A CARTOON COLON 1366 01:05:43,254 --> 01:05:43,687 CELL. 1367 01:05:43,687 --> 01:05:45,589 HERE IS TGF BETA AND THE 1368 01:05:45,589 --> 01:05:47,958 RECEPTOR AND OF COURSE WHAT 1369 01:05:47,958 --> 01:05:51,795 HAPPENS IS WHEN THE LIGAND TGF 1370 01:05:51,795 --> 01:05:56,166 BETA ENGAGE THE RECEPTOR IT 1371 01:05:56,166 --> 01:05:59,803 SENDS A SIGNAL TO THE NUCLEUS OF 1372 01:05:59,803 --> 01:06:03,974 THE CELL LEADING TO THE 1373 01:06:03,974 --> 01:06:07,244 APOPTOTIC CELL DEATHS AND THE 1374 01:06:07,244 --> 01:06:11,515 FINDING OF UBIQUITOUS IN THE 1375 01:06:11,515 --> 01:06:13,684 PATIENTS IN THE PATIENTS WITH 1376 01:06:13,684 --> 01:06:15,552 THE DEFECTIVE SPELL CHECKER LED 1377 01:06:15,552 --> 01:06:18,989 US TO REALIZE THERE WERE SEVERAL 1378 01:06:18,989 --> 01:06:19,323 IMPLICATIONS. 1379 01:06:19,323 --> 01:06:21,992 FIRST IT SAID THE TGF BETA TYPE 1380 01:06:21,992 --> 01:06:27,097 2 RECEPTOR IS A GENE MUTAT 1381 01:06:27,097 --> 01:06:30,467 MUTATIONALLY INACTIVATED IN 1382 01:06:30,467 --> 01:06:32,102 COLORECTAL CANCER AND THE 1383 01:06:32,102 --> 01:06:36,140 SIGNALLING PATHWAY WAS LIKELY A 1384 01:06:36,140 --> 01:06:38,942 TUMOR SUPPRESSER FUNCTION. 1385 01:06:38,942 --> 01:06:41,679 AND THIRDLY IT ESTABLISHED THESE 1386 01:06:41,679 --> 01:06:44,915 MUTATIONS AS PUNITIVE MECHANISMS 1387 01:06:44,915 --> 01:06:47,518 THAT CONNECT DEFECTS AND 1388 01:06:47,518 --> 01:06:49,453 MISMATCH REPAIR WITH THE 1389 01:06:49,453 --> 01:06:51,155 INACTIVATION OF THE TUMOR 1390 01:06:51,155 --> 01:06:52,289 SUPPRESSER GENE ENABLING THE 1391 01:06:52,289 --> 01:06:53,123 DEVELOPMENT OF COLON CANCERS IN 1392 01:06:53,123 --> 01:06:54,658 THE INDIVIDUALS. 1393 01:06:54,658 --> 01:06:57,861 SO TO TURN THIS INTO A SIMPLE 1394 01:06:57,861 --> 01:07:00,164 CARTOON, ONE CAN THINK OF TGF 1395 01:07:00,164 --> 01:07:04,768 BETA AS THE WALL OF APOPTOTIC 1396 01:07:04,768 --> 01:07:06,937 CELL DEATH IN THE COLON. 1397 01:07:06,937 --> 01:07:12,109 NORMALLY ALL COLON CANCERS ENTER 1398 01:07:12,109 --> 01:07:14,845 AN APOPTOTIC CELL DEATH PHASE 1399 01:07:14,845 --> 01:07:17,014 BUT THOSE WITH THE SPELL CHECKER 1400 01:07:17,014 --> 01:07:18,582 THERE'S A TIME BOMB UNDER THE 1401 01:07:18,582 --> 01:07:20,517 TGF BETA WALL OF DEATH AND WHEN 1402 01:07:20,517 --> 01:07:22,119 THE TIME BOMB RESULTS IN 1403 01:07:22,119 --> 01:07:23,620 MUTATIONS IN THE TGF BETA 1404 01:07:23,620 --> 01:07:26,924 RECEPTOR AND NOW YOU BLOW A HOLE 1405 01:07:26,924 --> 01:07:28,826 IN THE FUNCTIONAL MECHANISM AND 1406 01:07:28,826 --> 01:07:30,127 THE POTENTIAL CANCER CELLS 1407 01:07:30,127 --> 01:07:32,162 INSTEAD OF BEING SLOUGHED OFF 1408 01:07:32,162 --> 01:07:34,131 INTO THE LUMEN OF THE COLON AND 1409 01:07:34,131 --> 01:07:38,769 NOW PERSISTS AND PROGRESS. 1410 01:07:38,769 --> 01:07:41,205 SO WE HAVE THE BEGINNING OF A 1411 01:07:41,205 --> 01:07:44,441 PATHWAY IN WHICH LESIONS AND DNA 1412 01:07:44,441 --> 01:07:47,211 MISMATCH REPAIR TARGET THE TUMOR 1413 01:07:47,211 --> 01:07:49,513 SUPPRESSER GENE LEADING TO THE 1414 01:07:49,513 --> 01:07:51,715 ONSET OF YOUNG ONSET COLON 1415 01:07:51,715 --> 01:07:53,183 CANCERS TYPICALLY BEFORE THE AGE 1416 01:07:53,183 --> 01:07:55,386 OF 35 IN THE KINDREDS. 1417 01:07:55,386 --> 01:07:59,790 WE FURTHER VALIDATED TGF BETA 1418 01:07:59,790 --> 01:08:01,358 RECEPTORS WERE SUPPRESSER GENES 1419 01:08:01,358 --> 01:08:03,827 BY OF AND FINDING MUTATIONS AT 1420 01:08:03,827 --> 01:08:05,596 OTHER SITES IN THE GENE THAT 1421 01:08:05,596 --> 01:08:09,199 DEVELOPED INSPORADIC COLON 1422 01:08:09,199 --> 01:08:11,001 CANCERS IN WHICH THE DNA SPELL 1423 01:08:11,001 --> 01:08:14,671 CHECKER WAS OKAY AND THE TRACT 1424 01:08:14,671 --> 01:08:18,075 WAS NOT MUTATED BUT OTHER 1425 01:08:18,075 --> 01:08:22,146 REGIONS THE GENE COULD BE 1426 01:08:22,146 --> 01:08:25,015 TARGETED AND TOGETHER WE SHOWED 1427 01:08:25,015 --> 01:08:29,019 AN INDIVIDUAL IN THE TGF BETA 1428 01:08:29,019 --> 01:08:30,587 RECEPTOR WITH WILD TYPE IN THE 1429 01:08:30,587 --> 01:08:32,656 COLORECTAL CANCER IS THE 1430 01:08:32,656 --> 01:08:34,525 SIGNALLING PATHWAY WAS STILL 1431 01:08:34,525 --> 01:08:37,327 INACTIVATED AND THAT THROUGH 1432 01:08:37,327 --> 01:08:39,463 MUTATIONS IN THE SPLAT COMPLEX 1433 01:08:39,463 --> 01:08:42,065 CONNECT THE TGF BETA RECEPTORS 1434 01:08:42,065 --> 01:08:48,305 WITH THE NUCLEUS AND WHAT WOULD 1435 01:08:48,305 --> 01:08:50,374 MATTER SO MUCH THAT THIS PATHWAY 1436 01:08:50,374 --> 01:08:54,178 WOULD BE UNDER THIS EXQUISITE 1437 01:08:54,178 --> 01:08:56,380 PRESSURE FROM MUTATIONAL 1438 01:08:56,380 --> 01:08:56,713 INACTIVATION? 1439 01:08:56,713 --> 01:08:57,748 TO ADDRESS THAT QUESTION WE DID 1440 01:08:57,748 --> 01:09:01,251 AN EARLY FORM OF WHAT TODAY 1441 01:09:01,251 --> 01:09:04,354 WOULD BE CONSIDERED A BIO 1442 01:09:04,354 --> 01:09:05,389 INFORMATICS EXPERIMENT AND USED 1443 01:09:05,389 --> 01:09:08,325 EXPRESSION MICROARRAYS DEVELOPED 1444 01:09:08,325 --> 01:09:17,401 AT THAT TIME TO ASK A BULIAN 1445 01:09:17,401 --> 01:09:20,571 ENQUESTION OF HOW MANY WERE 1446 01:09:20,571 --> 01:09:24,741 TURNED OFF IN COLORECTAL 1447 01:09:24,741 --> 01:09:25,075 CANCERS. 1448 01:09:25,075 --> 01:09:27,244 WHILE THERE'S THOUSANDS OF GENES 1449 01:09:27,244 --> 01:09:30,481 DOWN REGULATED IN COLON CANCER 1450 01:09:30,481 --> 01:09:32,749 WE FOUND THERE WERE ONLY EIGHT 1451 01:09:32,749 --> 01:09:35,285 GENES UPREGULATED BY TEN FOLD OR 1452 01:09:35,285 --> 01:09:38,989 MORE BY TGF BETA IN THE NORMAL 1453 01:09:38,989 --> 01:09:40,624 COLON AND ONLY 25 DOWN REGULATED 1454 01:09:40,624 --> 01:09:43,060 BY 10 OR MORE IN COLON CANCER 1455 01:09:43,060 --> 01:09:45,362 AND ONLY ONE GENE MET BOTH 1456 01:09:45,362 --> 01:09:55,906 CONDITIONS AND THAT WAS 15 PR 1457 01:10:01,278 --> 01:10:03,113 PROSTAGLAND AND IT DIDN'T 1458 01:10:03,113 --> 01:10:06,183 CONNECT TO CANCER OF ANY KIND IN 1459 01:10:06,183 --> 01:10:16,426 MODEL SYSTEMS. 1460 01:10:17,528 --> 01:10:20,097 WHEN WE ASKED WHAT IT DID WE 1461 01:10:20,097 --> 01:10:22,566 BEGAN TO FORMULATE A HYPOTHESIS 1462 01:10:22,566 --> 01:10:24,101 BECAUSE IT TURNED OUT TO ENCODE 1463 01:10:24,101 --> 01:10:25,836 AN ENZYME. 1464 01:10:25,836 --> 01:10:31,408 THE FUNCTION WAS TO CATALYZE THE 1465 01:10:31,408 --> 01:10:35,078 DE INSTRUCTION OF THE 1466 01:10:35,078 --> 01:10:37,981 PROSTAGLANDIN 2 AND OXIDIZES TO 1467 01:10:37,981 --> 01:10:41,485 THE GROUP ON THE MODEL AND THAT 1468 01:10:41,485 --> 01:10:45,589 INACTIVATES THE PGE2 TO ACT AS A 1469 01:10:45,589 --> 01:10:46,056 LIGAND AND TO SIGNAL. 1470 01:10:46,056 --> 01:10:46,123 1471 01:10:56,633 --> 01:10:58,602 AND IT WAS A GROWTH FACTOR IN 1472 01:10:58,602 --> 01:11:02,205 THE COLON AND KNOWN TO BE 1473 01:11:02,205 --> 01:11:04,474 INCREASED IN COLORECTAL CANCER 1474 01:11:04,474 --> 01:11:09,313 BY THE ACTIVATION OF THE COX 2 1475 01:11:09,313 --> 01:11:17,254 ENZYME THAT SYNTHESIZES IT AND 1476 01:11:17,254 --> 01:11:19,423 RECEPTORS HAD BEEN IDENTIFIED 1477 01:11:19,423 --> 01:11:23,360 AND ALL G PROTEIN COUPLED 1478 01:11:23,360 --> 01:11:25,462 RECEPTORS AND SHOWED THEY COULD 1479 01:11:25,462 --> 01:11:32,069 SIGNAL THROUGH CYCLIN D1 AND 1480 01:11:32,069 --> 01:11:33,403 ACTIVATE MIGRATION AND ALL 1481 01:11:33,403 --> 01:11:35,872 PHENOTYPES ASSOCIATED WITH 1482 01:11:35,872 --> 01:11:36,139 NEOPLASIA. 1483 01:11:36,139 --> 01:11:45,415 SO WE HYPOTHESIZED THAT PERHAPS 1484 01:11:45,415 --> 01:11:47,017 15PGDH HAD BEEN OVERLOOKED AND 1485 01:11:47,017 --> 01:11:49,052 MAY BE ABLE TO DOWN REGULATE THE 1486 01:11:49,052 --> 01:11:50,220 PATHWAY AND ENABLE ITS 1487 01:11:50,220 --> 01:11:53,757 HOMEOSTATIC CONTROL. 1488 01:11:53,757 --> 01:11:55,892 SO TO EXPLORE THAT HYPOTHESIS WE 1489 01:11:55,892 --> 01:12:00,664 WERE ABLE TO OBTAIN THE KNOCKOUT 1490 01:12:00,664 --> 01:12:03,000 MOUSE JUST MADE BY BETH KOLLERS 1491 01:12:03,000 --> 01:12:05,836 LAB AT THE UNIVERSITY OF NORTH 1492 01:12:05,836 --> 01:12:06,103 CAROLINA. 1493 01:12:06,103 --> 01:12:07,471 SHE GRACIOUSLY SHARED THAT MOUSE 1494 01:12:07,471 --> 01:12:12,309 WITH US AND THE MOUSE WAS ON A 1495 01:12:12,309 --> 01:12:18,181 C57 BLACK BACKGROUND NOTORIOUSLY 1496 01:12:18,181 --> 01:12:19,583 RESISTANT TO THE INDUCTION OF 1497 01:12:19,583 --> 01:12:21,351 COLON TUMORS. 1498 01:12:21,351 --> 01:12:24,321 INDEED WHEN WE TREATED A WILD 1499 01:12:24,321 --> 01:12:26,189 TYPE C57 BLACK 6 MOUSE WE COULD 1500 01:12:26,189 --> 01:12:29,159 NOT INDUCE COLON TUMORS. 1501 01:12:29,159 --> 01:12:33,764 BUT WHEN WE TREATED THE KNOCKOUT 1502 01:12:33,764 --> 01:12:35,399 MOUSE WE FOUND THEY WERE 1503 01:12:35,399 --> 01:12:36,900 SUSCEPTIBLE TO THE 1504 01:12:36,900 --> 01:12:38,669 CARCINOGENESIS AND YOU CAN SEE 1505 01:12:38,669 --> 01:12:41,204 ONE SUCH TUMOR AND WHEN WE DID 1506 01:12:41,204 --> 01:12:44,141 THIS EXPERIMENT ACROSS A COHORT 1507 01:12:44,141 --> 01:12:46,376 OF MICE, NONE OF THE WILD TYPE 1508 01:12:46,376 --> 01:12:49,246 MICE THAT WERE CARCINOGEN 1509 01:12:49,246 --> 01:12:55,185 EXPOSED DEVELOPED TUMORS BUT THE 1510 01:12:55,185 --> 01:12:58,622 HETTER ZYGOUS MOUSE DEVELOPED 1511 01:12:58,622 --> 01:13:01,358 COLON TUMORS WITH TUBULAR 1512 01:13:01,358 --> 01:13:04,594 ADENOMAS IN YELLOW WITH HIGH 1513 01:13:04,594 --> 01:13:05,462 GRADE DYSPLASIA SHOWN IN RED. 1514 01:13:05,462 --> 01:13:07,798 AND WE ASKED WHAT WAS GOING ON 1515 01:13:07,798 --> 01:13:09,466 AT THE MICROSCOPIC LEVEL AND IF 1516 01:13:09,466 --> 01:13:12,269 WE LOOKED AT CARCINOGEN TREATED 1517 01:13:12,269 --> 01:13:15,472 MICE COLONS FROM A WILD TYPE OR 1518 01:13:15,472 --> 01:13:18,208 KNOCKOUT MOUSE, WHAT YOU CAN SEE 1519 01:13:18,208 --> 01:13:19,342 IS IN THE WILD TYPE MOUSE THERE 1520 01:13:19,342 --> 01:13:21,511 IS A LESION. 1521 01:13:21,511 --> 01:13:24,781 YOU HAVE THIS LARGE CRYPT BUT 1522 01:13:24,781 --> 01:13:30,654 IT'S HISTOLOGICALLY BLAND IN THE 1523 01:13:30,654 --> 01:13:32,355 KNOCKOUT MOUSE THERE'S BEEN 1524 01:13:32,355 --> 01:13:34,191 PROLIFERATION AND ONE CAN 1525 01:13:34,191 --> 01:13:38,028 VISUALIZE THAT BY STAINING THE 1526 01:13:38,028 --> 01:13:42,499 LESIONS WITH THE PROLIFIC MARKER 1527 01:13:42,499 --> 01:13:44,668 AND THE LARGE CRYPTS ARE 1528 01:13:44,668 --> 01:13:47,337 ESPECIALLY SHUT DOWN. 1529 01:13:47,337 --> 01:13:48,839 THEY'RE NOT PROLIFERATING 1530 01:13:48,839 --> 01:13:50,006 PARTICULARLY RAPIDLY AND IN THE 1531 01:13:50,006 --> 01:13:52,743 KNOCKOUT MOUSE YOU SEE THE 1532 01:13:52,743 --> 01:13:55,345 PROLIFERATIVE CELLS AND GOING UP 1533 01:13:55,345 --> 01:13:58,181 TO THE TO THE OF THE CRYPT WHERE 1534 01:13:58,181 --> 01:14:00,050 NORMALLY YOU'D SEE APOPTOTIC 1535 01:14:00,050 --> 01:14:02,152 CELL DEATH AND WHAT IS DRIVING 1536 01:14:02,152 --> 01:14:05,288 THIS IS THE CYCLIN D1 PATHWAY 1537 01:14:05,288 --> 01:14:08,125 YOU CAN VISUALIZE AND SEEING THE 1538 01:14:08,125 --> 01:14:10,160 NUCLEAR LOCALIZATION IN THE 1539 01:14:10,160 --> 01:14:12,262 KNOCKOUT MOUSE AND ONE CAN 1540 01:14:12,262 --> 01:14:14,164 QUANTITATE THIS AND SEE IN THE 1541 01:14:14,164 --> 01:14:23,607 WILD TYPE MOUSE AND STIPALED 1542 01:14:23,607 --> 01:14:27,911 MOUSE THE ACTIVATION OF CYCLIN 1543 01:14:27,911 --> 01:14:28,612 D1 PATHWAY. 1544 01:14:28,612 --> 01:14:30,113 SO WHAT WE WERE ABLE TO PUT 1545 01:14:30,113 --> 01:14:32,015 TOGETHER WAS A ROUGH OUTLINE OF 1546 01:14:32,015 --> 01:14:35,018 WHAT WAS HAPPENING. 1547 01:14:35,018 --> 01:14:44,528 IT WAS UNDERSTOOD THAT COX-2 WAS 1548 01:14:44,528 --> 01:14:46,930 UPREGULATED AND INCREASED 1549 01:14:46,930 --> 01:14:49,232 PROSTAGLANDIN AND THAT WAS 1550 01:14:49,232 --> 01:14:50,700 ASSOCIATED WITH THE COLON 1551 01:14:50,700 --> 01:14:51,935 ADENOMAS AND WERE ABLE TO SHOW 1552 01:14:51,935 --> 01:14:54,171 WHAT IS GOING ON IS IF YOU HAVE 1553 01:14:54,171 --> 01:14:56,773 A MUTATED CELL OR INITIATED CELL 1554 01:14:56,773 --> 01:15:00,510 IN THE CRYPT OF A COLON, IT'S 1555 01:15:00,510 --> 01:15:08,351 OFTEN QUIESCENT BUT THIS GIVES 1556 01:15:08,351 --> 01:15:12,255 RISE TO THESE PRECURSOR REGIONS 1557 01:15:12,255 --> 01:15:14,524 THE ADENOMAS AND ITS NORMALLY 1558 01:15:14,524 --> 01:15:18,361 HAS A PHYSIOLOGIC REGULATOR IN 1559 01:15:18,361 --> 01:15:24,201 THE FORM OF 15-PGDH AND 1560 01:15:24,201 --> 01:15:29,606 REGULATION OF TGF-BETA AND THERE 1561 01:15:29,606 --> 01:15:32,209 WAS UNDER APPRECIATED CROSS TALK 1562 01:15:32,209 --> 01:15:33,977 THAT ALLOWED IT TO NEGATIVELY 1563 01:15:33,977 --> 01:15:34,511 REGULATE THE CELLS. 1564 01:15:34,511 --> 01:15:38,415 WE HAD A SIMPLE STORY. 1565 01:15:38,415 --> 01:15:40,383 LOW PGDH IS BAD FOR YOU AND 1566 01:15:40,383 --> 01:15:43,787 ALLOWS FOR PROLIFERATION IN THE 1567 01:15:43,787 --> 01:15:44,221 COLON. 1568 01:15:44,221 --> 01:15:46,890 THE FLY IN THE OINTMENT, IF YOU 1569 01:15:46,890 --> 01:15:48,859 WILL, WAS WHEN WE MEASURED 1570 01:15:48,859 --> 01:15:53,897 LEVELS OF PGDH IN THE COLON 1571 01:15:53,897 --> 01:15:56,600 ACROSS INDIVIDUALS WE FOUND 1572 01:15:56,600 --> 01:15:59,669 HETERODISPERSION IN THE 1573 01:15:59,669 --> 01:16:01,771 POPULATIONS AND LEVELS ACROSS A 1574 01:16:01,771 --> 01:16:02,205 GROUP OF PATIENTS. 1575 01:16:02,205 --> 01:16:03,540 I THINK 20 IN NUMBER. 1576 01:16:03,540 --> 01:16:06,176 YOU CAN SEE THERE'S NEARLY A 1577 01:16:06,176 --> 01:16:07,510 12-POINT RANGE IN THE HUMAN 1578 01:16:07,510 --> 01:16:08,812 POPULATION WITH VERY LONG TAIL 1579 01:16:08,812 --> 01:16:12,282 OF INDIVIDUALS WITH VERY LOW 1580 01:16:12,282 --> 01:16:14,951 LEVELS OF COLONIC PGDH. 1581 01:16:14,951 --> 01:16:17,287 WHEN YOU SEE THIS KIND OF 1582 01:16:17,287 --> 01:16:19,856 GENETIC SIGNAL IT USUALLY MEANS 1583 01:16:19,856 --> 01:16:22,025 YOU'VE MISSED HALF THE STORY AND 1584 01:16:22,025 --> 01:16:24,094 THERE IS SOME SELECTIVE 1585 01:16:24,094 --> 01:16:25,528 ADVANTAGE FOR INDIVIDUALS WITH 1586 01:16:25,528 --> 01:16:26,529 LOW PGDH. 1587 01:16:26,529 --> 01:16:29,099 THE QUESTION IS WHAT WOULD THAT 1588 01:16:29,099 --> 01:16:31,601 SELECTIVE ADVANTAGE BE? 1589 01:16:31,601 --> 01:16:32,969 OF COURSE THROUGH MUCH OF 1590 01:16:32,969 --> 01:16:33,904 EVOLUTION THE CONCERN WITH 1591 01:16:33,904 --> 01:16:36,840 EVOLUTION IS NOT PROTECTING YOUR 1592 01:16:36,840 --> 01:16:38,775 COLON FROM PROLIFERATING IN YOUR 1593 01:16:38,775 --> 01:16:42,178 OLD AGE BUT RATHER ENABLING YOU 1594 01:16:42,178 --> 01:16:45,015 TO SURVIVE INFECTIONS. 1595 01:16:45,015 --> 01:16:48,451 ENABLING YOU TO SURVIVE 1596 01:16:48,451 --> 01:16:58,995 INFECTIOUS DIARRHEAS -- AND 1597 01:17:03,099 --> 01:17:06,603 REPAIR THE DAMAGE TO THE MUCOSA 1598 01:17:06,603 --> 01:17:09,039 AND THOUGHT WE COULD LOOK AT THE 1599 01:17:09,039 --> 01:17:11,474 REPAIR OF THE MODEL AND THE 1600 01:17:11,474 --> 01:17:15,578 MODEL WE CHOSE WAS ULCERATIVE 1601 01:17:15,578 --> 01:17:17,547 COLITIS WHERE MICE ARE FED A 1602 01:17:17,547 --> 01:17:19,749 CHEMICAL IN THE DIET, AND YOU 1603 01:17:19,749 --> 01:17:24,621 CAN SEE IN THE MOUSE COLONOSCOPY 1604 01:17:24,621 --> 01:17:27,390 THE MICE DEVELOPED THE WHITE 1605 01:17:27,390 --> 01:17:29,159 ULCERATIONS UNDER THE MICROSCOPE 1606 01:17:29,159 --> 01:17:30,961 AND THIS IS AN EPITHELIAL ULCER 1607 01:17:30,961 --> 01:17:36,433 WHERE IT'S GONE AND THESE ARE 1608 01:17:36,433 --> 01:17:36,766 INFLAMMATORY. 1609 01:17:36,766 --> 01:17:41,972 WE FOUND WE COULD WITH DSF 1610 01:17:41,972 --> 01:17:44,607 ULCERATE ABOUT 8% OF THE COLON 1611 01:17:44,607 --> 01:17:47,344 OF THIS WILD TYPE MOUSE AND THE 1612 01:17:47,344 --> 01:17:48,812 KNOCKOUT MOUSE WAS COMPLETELY 1613 01:17:48,812 --> 01:17:49,079 RESISTANT. 1614 01:17:49,079 --> 01:17:51,214 THERE WERE NO ULCERS WHATSOEVER 1615 01:17:51,214 --> 01:17:53,717 IN THE KNOCKOUT MOUSE. 1616 01:17:53,717 --> 01:17:56,987 EVEN IN AREAS WHERE THE 1617 01:17:56,987 --> 01:17:59,189 EPITHELIUM REMAINED VISIBLY IN 1618 01:17:59,189 --> 01:18:04,094 THE COLONO SCOPE IN THE WILD 1619 01:18:04,094 --> 01:18:06,196 TYPE THE EPITHELIUM WAS BEING 1620 01:18:06,196 --> 01:18:08,631 ERODED UNDERNEATH AND IN THE 1621 01:18:08,631 --> 01:18:09,833 KNOCKOUT MOUSE THERE WERE NO 1622 01:18:09,833 --> 01:18:14,037 EROSIONS WHATSOEVER AND COULD 1623 01:18:14,037 --> 01:18:17,440 QUANTITATE THIS SHOWING THIS 1624 01:18:17,440 --> 01:18:18,074 CRYPTITIS OCCURRING UNDERNEATH 1625 01:18:18,074 --> 01:18:21,277 THE EPITHELIUM OF THE WILD TYPE 1626 01:18:21,277 --> 01:18:24,114 MOUSE AND NEAR COMPLETE 1627 01:18:24,114 --> 01:18:25,715 RESISTANCE TO THE LOSS OF CRYPTS 1628 01:18:25,715 --> 01:18:27,117 IN THE KNOCKOUT MOUSE. 1629 01:18:27,117 --> 01:18:33,123 WHEN WE ASKED WHY WAS THE 1630 01:18:33,123 --> 01:18:39,696 KNOCKOUT MOUSE RESISTANT TO THE 1631 01:18:39,696 --> 01:18:42,165 ULCERATIONS THESE ARE SHOWN IN 1632 01:18:42,165 --> 01:18:44,267 THE FLUORESCENT STRAIN AND THE 1633 01:18:44,267 --> 01:18:45,935 RED DOTS ARE THE PROLIFERATING 1634 01:18:45,935 --> 01:18:48,972 CELLS AND IF THIS IS A NORMAL 1635 01:18:48,972 --> 01:18:51,374 WILD TYPE MOUSE YOU CAN SEE WHEN 1636 01:18:51,374 --> 01:18:53,810 THE MOUSE IS FED DSS BY THE 1637 01:18:53,810 --> 01:18:54,944 EIGHTH DAY OF EXPOSURE, MOST OF 1638 01:18:54,944 --> 01:18:56,312 THE RED DOTS ARE GONE. 1639 01:18:56,312 --> 01:18:58,081 MOST THE PROLIFERATING CELLS 1640 01:18:58,081 --> 01:18:58,715 HAVE BEEN KILLED OFF. 1641 01:18:58,715 --> 01:19:02,318 BUT IF YOU LOOK AT THE KNOCKOUT 1642 01:19:02,318 --> 01:19:05,855 MOUSE IT STARTS LOOKING JUST 1643 01:19:05,855 --> 01:19:07,791 LIKE THE WILD TYPE MOUSE BUT IN 1644 01:19:07,791 --> 01:19:10,193 THE FACE OF THE STRESS IT'S 1645 01:19:10,193 --> 01:19:14,164 ACTUALLY ABLE TO UPREGULATE THE 1646 01:19:14,164 --> 01:19:17,567 PROLIFERATION AND REPLENISH THE 1647 01:19:17,567 --> 01:19:21,304 COLONS AS FAST AS THE CELLS ARE 1648 01:19:21,304 --> 01:19:24,307 KILLED OFF AND THEN UNTREATED 1649 01:19:24,307 --> 01:19:27,343 THE WILD TYPE MOUSE LOSES 1650 01:19:27,343 --> 01:19:28,011 PROLIFERATIVE MOUSE THE KNOCKOUT 1651 01:19:28,011 --> 01:19:31,948 MOUSE GAINS THEM. 1652 01:19:31,948 --> 01:19:35,218 SO, IT APPEARS UNDER SEVERAL 1653 01:19:35,218 --> 01:19:38,254 CONTEXT HAVING LOW ACTIVITY OF 1654 01:19:38,254 --> 01:19:43,159 THE DATA SIGNALLING PATHWAY IS 1655 01:19:43,159 --> 01:19:44,928 ACTUALLY GOOD FOR YOU BECAUSE IT 1656 01:19:44,928 --> 01:19:46,729 ALLOWS YOU TO REPAIR TISSUE 1657 01:19:46,729 --> 01:19:46,996 DAMAGE. 1658 01:19:46,996 --> 01:19:49,666 WE WONDERED COULD WE DEVELOP A 1659 01:19:49,666 --> 01:19:52,769 DRUG THAT WOULD ALLOW US TO SHUT 1660 01:19:52,769 --> 01:19:53,570 THIS PATHWAY OFF IN THE CONTEXT 1661 01:19:53,570 --> 01:19:55,405 OF DISEASES WHERE YOU MIGHT WANT 1662 01:19:55,405 --> 01:19:59,142 TO SHUT IT OFF? 1663 01:19:59,142 --> 01:20:03,580 WE USED GENETIC ENGINEERING 1664 01:20:03,580 --> 01:20:05,782 TECHNOLOGY AND YOU CAN SEE CELLS 1665 01:20:05,782 --> 01:20:09,986 AND VISUALIZE THE LEVEL OF PGDH 1666 01:20:09,986 --> 01:20:12,489 BY HOW MUCH LIGHT THE CELLS ARE 1667 01:20:12,489 --> 01:20:14,324 GIVING OFF AND USED THAT ASSAY 1668 01:20:14,324 --> 01:20:16,860 TO SCREEN A QUARTER OF A MILLION 1669 01:20:16,860 --> 01:20:18,461 SMALL MOLECULES WITH 1670 01:20:18,461 --> 01:20:20,497 COLLABORATION WITH A TEAM AT THE 1671 01:20:20,497 --> 01:20:21,064 UNIVERSITY OF TEXAS SEARCH 1672 01:20:21,064 --> 01:20:24,734 WARRANT. 1673 01:20:24,734 --> 01:20:27,036 -- SOUTHWESTERN AND OUT OF THAT 1674 01:20:27,036 --> 01:20:30,240 SCREEN WE IDENTIFIED THIS 1675 01:20:30,240 --> 01:20:36,880 MOLECULE AS SWO33291 WHICH WAS 1676 01:20:36,880 --> 01:20:40,617 POTENT IN INHIBITING THE 1677 01:20:40,617 --> 01:20:42,652 ENZYMATIC ACTIVITY AND HAD A 1678 01:20:42,652 --> 01:20:45,255 BINDING CONSTANT OF LESS THAN 1679 01:20:45,255 --> 01:20:52,028 ONE NANOMOLE AR FOR INHIBITING 1680 01:20:52,028 --> 01:20:56,633 THE PDGH AND STABLE AND ACTIVE 1681 01:20:56,633 --> 01:20:58,868 WHEN INJECTED INTO MICE AND SEE 1682 01:20:58,868 --> 01:21:02,672 IT AGAIN THE DISEASE PATTERN OF 1683 01:21:02,672 --> 01:21:06,176 A WILD TYPE MOUSE THE DSS AND 1684 01:21:06,176 --> 01:21:08,978 THE INDUCTION OF THE ULCERS THE 1685 01:21:08,978 --> 01:21:11,948 PREVENTION BY KNOCKING OUT PDGH 1686 01:21:11,948 --> 01:21:20,390 AND THE PREVENTION OF THE ULCERS 1687 01:21:20,390 --> 01:21:22,559 BY GIVING THE DRUG AND SAME IS 1688 01:21:22,559 --> 01:21:26,162 TRUE ALSO FOR THE CRYPTITIS 1689 01:21:26,162 --> 01:21:26,429 SCORE. 1690 01:21:26,429 --> 01:21:32,602 SO NOW WE HAD A PICTURE THAT 1691 01:21:32,602 --> 01:21:38,508 SAID NORMALLY YOU HAVE THE 1692 01:21:38,508 --> 01:21:42,745 PROSTAGLANDIN AND PRODUCED BY 1693 01:21:42,745 --> 01:21:48,618 COX 1 OR COX 2 AND IN THE 1694 01:21:48,618 --> 01:21:54,057 TISSUES THE LEVEL OF PGDH2 IS 1695 01:21:54,057 --> 01:21:57,393 REGULATED BY THE COMPLEX. 1696 01:21:57,393 --> 01:22:00,496 IF WE DISTRIBUTE THE INHIBITOR 1697 01:22:00,496 --> 01:22:11,040 WE CAN NOW BLOCK THAT KETABOLIC 1698 01:22:14,777 --> 01:22:18,881 PATHWAY AND POTENTIATES THE 1699 01:22:18,881 --> 01:22:19,782 PROLIFERATING CELL. 1700 01:22:19,782 --> 01:22:22,752 AND WE NOW HAVE HAD A CHEMICAL 1701 01:22:22,752 --> 01:22:24,821 PROBE WE COULD DO CHEMICAL 1702 01:22:24,821 --> 01:22:26,155 BIOLOGY AND LOOKED AT HOW 1703 01:22:26,155 --> 01:22:28,791 CONSERVED THE PATHWAY WAS. 1704 01:22:28,791 --> 01:22:34,931 AND WE FOUND INHIBITING COULD 1705 01:22:34,931 --> 01:22:37,200 POTENTIATE REPAIR AFTER INJURY 1706 01:22:37,200 --> 01:22:38,501 TO THE LIVER AND COULD 1707 01:22:38,501 --> 01:22:40,536 POTENTIATE REPAIR IN THE BONE 1708 01:22:40,536 --> 01:22:43,973 MARROW AND IN EXPERIMENTS WE 1709 01:22:43,973 --> 01:22:48,911 SHOWED WE COULD MARKEDLY 1710 01:22:48,911 --> 01:22:53,416 UPREGULATE THE POPULATION OF THE 1711 01:22:53,416 --> 01:22:54,851 HEMATOPOIETIC SYSTEM THROUGH 1712 01:22:54,851 --> 01:22:56,085 UPREGULATE THE BONE MARROW AND 1713 01:22:56,085 --> 01:23:00,957 TURNING ON THE PRODUCTION OF TWO 1714 01:23:00,957 --> 01:23:04,460 STEM CELL CYTOKINES AND XCL12. 1715 01:23:04,460 --> 01:23:07,063 HOW IS IT THE MOLECULE IS SO 1716 01:23:07,063 --> 01:23:07,297 POTENT? 1717 01:23:07,297 --> 01:23:09,866 HOW DID WE GET TO LUCKY? 1718 01:23:09,866 --> 01:23:12,535 TWO YEARS AGO WE WERE ABLE TO 1719 01:23:12,535 --> 01:23:15,838 SOLVE THE CRYO EM STRUCTURE OF 1720 01:23:15,838 --> 01:23:20,543 THE FAMILY OF DRUG ABOUT TO 1721 01:23:20,543 --> 01:23:21,177 15PDGH. 1722 01:23:21,177 --> 01:23:30,153 THE STUDY SHOWED ITSELF IS A 1723 01:23:30,153 --> 01:23:33,122 HOMO DIMER AND THE MOLECULE 1724 01:23:33,122 --> 01:23:38,227 BOUND TO THE PROTEIN AND YOU SEE 1725 01:23:38,227 --> 01:23:40,496 THE OBVIOUS MYSTERY WHICH IS THE 1726 01:23:40,496 --> 01:23:43,499 DRUG IS BURIED DEEP INSIDE THE 1727 01:23:43,499 --> 01:23:43,733 PROTEIN. 1728 01:23:43,733 --> 01:23:46,002 SO HOW IN THE WORLD DID IT GET 1729 01:23:46,002 --> 01:23:47,837 THERE AND GET INSIDE. 1730 01:23:47,837 --> 01:23:51,207 WE HAVE A SHIP IN THE BOTTLE 1731 01:23:51,207 --> 01:23:51,441 PROBLEM. 1732 01:23:51,441 --> 01:23:53,509 IT TURNED OUT TO BE THE GOLD 1733 01:23:53,509 --> 01:23:55,345 HELIX CAN MOVE AND FUNCTION AS A 1734 01:23:55,345 --> 01:23:59,048 TRAP DOOR TO OPEN AND CLOSE AND 1735 01:23:59,048 --> 01:24:03,453 REVEAL THIS HIDDEN POCKET IN 1736 01:24:03,453 --> 01:24:03,686 15PDGH. 1737 01:24:03,686 --> 01:24:05,655 AND THE TRAP DOOR MECHANISM 1738 01:24:05,655 --> 01:24:08,124 TURNS OUT TO BE PHYSIOLOGIC. 1739 01:24:08,124 --> 01:24:09,892 THE POCKET IS THE POCKET BY 1740 01:24:09,892 --> 01:24:14,630 WHICH PG2 NORMALLY BINDS TO 1741 01:24:14,630 --> 01:24:18,601 52PDGH AND WHEN THE DOOR CLOSES 1742 01:24:18,601 --> 01:24:23,539 THE MECHANISM BY THE TWO AMINO 1743 01:24:23,539 --> 01:24:28,244 ACIDS CAN DESTROY PDG2 AND 1744 01:24:28,244 --> 01:24:30,012 THEY'RE WIRING THE DOOR SHUT. 1745 01:24:30,012 --> 01:24:32,348 SO WHEN THE TRAP DOOR CLOSES ON 1746 01:24:32,348 --> 01:24:35,818 THE DRUG AS YOU SAW IN THE CRYO 1747 01:24:35,818 --> 01:24:38,187 EM STRUCTURE IT BINDS TO THE 1748 01:24:38,187 --> 01:24:42,058 DOOR AND NOW THE ENZYME IS 1749 01:24:42,058 --> 01:24:42,692 INACTIVATED. 1750 01:24:42,692 --> 01:24:45,828 SINCE THE INITIAL PUBLICATION, 1751 01:24:45,828 --> 01:24:48,097 WE'VE IDENTIFIED THIS PATHWAY IS 1752 01:24:48,097 --> 01:24:50,733 CONSERVED AND ENGAGED IN 1753 01:24:50,733 --> 01:24:52,201 MULTIPLE AND WHAT WE SEE IN 1754 01:24:52,201 --> 01:24:54,270 MODELS OF HUMAN DISEASE 1755 01:24:54,270 --> 01:24:56,439 INCLUDING REGULATING THE BONE 1756 01:24:56,439 --> 01:25:02,812 MARROW RECOVERY AFTER BONE 1757 01:25:02,812 --> 01:25:06,015 MARROW TRANSPLANTATION AND 1758 01:25:06,015 --> 01:25:09,385 REGULATING THE RATE OF 1759 01:25:09,385 --> 01:25:12,355 DEVELOPMENT OF APLASTIC ANEMIA 1760 01:25:12,355 --> 01:25:15,925 AND ENABLING PROTECTION FROM 1761 01:25:15,925 --> 01:25:20,696 ISCHEMIC INJURY AND THE 1762 01:25:20,696 --> 01:25:22,965 REGULATION OF TISSUE REPAIR 1763 01:25:22,965 --> 01:25:25,401 TURNS OUT TO BE DEEPLY CONSERVED 1764 01:25:25,401 --> 01:25:27,236 ACROSS MULTIPLE TISSUES IN THE 1765 01:25:27,236 --> 01:25:28,805 MOUSE BODY AND HOPEFULLY IN THE 1766 01:25:28,805 --> 01:25:31,707 HUMAN AS WELL AND WITH THAT 1767 01:25:31,707 --> 01:25:33,009 UNDERSTANDING WE WANTED TO GO 1768 01:25:33,009 --> 01:25:34,744 FORWARD AND SEE IF WE COULD 1769 01:25:34,744 --> 01:25:36,078 BRING THIS FORWARD FOR POTENTIAL 1770 01:25:36,078 --> 01:25:38,181 HUMAN USE. 1771 01:25:38,181 --> 01:25:41,017 WE WERE ABLE TO COME UP WITH THE 1772 01:25:41,017 --> 01:25:44,086 ACCELERATOR LIFE SCIENCE 1773 01:25:44,086 --> 01:25:50,426 PARTNERS FOR A BIO TECH START 1774 01:25:50,426 --> 01:25:53,729 UP AND WERE CAPITALIZED BY A 1775 01:25:53,729 --> 01:25:56,632 NUMBER OF LARGE PHARMACEUTICAL 1776 01:25:56,632 --> 01:26:04,006 COMPANIES AND ABBVIE AND LILY 1777 01:26:04,006 --> 01:26:05,475 AND JOHNSON AND JOHNSON AND MUCH 1778 01:26:05,475 --> 01:26:09,312 TO OUR SURPRISE IN 2021, AMGEN 1779 01:26:09,312 --> 01:26:12,114 CAME KNOCKING ON THE DOOR AND 1780 01:26:12,114 --> 01:26:15,918 SAID THEY WERE INTERESTED AND 1781 01:26:15,918 --> 01:26:16,719 ACQUIRED THE LICENSE TO THE 1782 01:26:16,719 --> 01:26:18,020 COMPOUNDS WE DEVELOPED AND ARE 1783 01:26:18,020 --> 01:26:19,522 NOW CARRYING THE TECHNOLOGY 1784 01:26:19,522 --> 01:26:21,090 FORWARD CURRENTLY IN PRECLINICAL 1785 01:26:21,090 --> 01:26:23,025 DRUG DEVELOPMENT. 1786 01:26:23,025 --> 01:26:27,230 SO WE HOPE WE WILL SEE THE 1787 01:26:27,230 --> 01:26:29,098 POTENTIAL OF THIS PATHWAY TESTED 1788 01:26:29,098 --> 01:26:34,036 IN THE MODELS OF HUMAN DISEASE. 1789 01:26:34,036 --> 01:26:44,547 SO, WE WENT FROM THE MISMATCH 1790 01:26:48,618 --> 01:26:50,086 REPAIR SYSTEM TO IDENTIFYING 1791 01:26:50,086 --> 01:26:52,488 MUTATIONS IN THE BETA RECEPTORS, 1792 01:26:52,488 --> 01:26:56,659 IDENTIFYING A PATHWAY THAT 1793 01:26:56,659 --> 01:27:02,498 ULTIMATELY CONVERGED ON 15PDGH 1794 01:27:02,498 --> 01:27:07,136 AND INHIBIT THE SIGNALLING. 1795 01:27:07,136 --> 01:27:08,604 BUT AS THE ANOTHER BIG HUGE 1796 01:27:08,604 --> 01:27:12,174 QUESTION, THE GORILLA IN THE 1797 01:27:12,174 --> 01:27:12,375 ROOM. 1798 01:27:12,375 --> 01:27:17,613 WHILE SHE SYNDROME ACCOUNTS FOR 1799 01:27:17,613 --> 01:27:21,784 5% OF THE COLORECTAL CANCERS THE 1800 01:27:21,784 --> 01:27:25,187 TGF BETA SIGNALLING PATHWAY AND 1801 01:27:25,187 --> 01:27:29,125 THE MNEMONIC MUTATION AND THE 1802 01:27:29,125 --> 01:27:32,562 TRACK OF THE RGF BETA 2 WAS 1803 01:27:32,562 --> 01:27:35,831 FOUND IN 15% OF COLORECTAL 1804 01:27:35,831 --> 01:27:39,268 CANCERS AND FOUND IN NEARLY HALF 1805 01:27:39,268 --> 01:27:41,837 THAT AROSE IN THE RIGHT SIDE IN 1806 01:27:41,837 --> 01:27:46,175 THE ASCENDING COLON. 1807 01:27:46,175 --> 01:27:49,178 WE AND MANY OTHER LABORATORIES 1808 01:27:49,178 --> 01:27:52,181 TRIED TO UNDERSTAND HOW THIS 1809 01:27:52,181 --> 01:27:54,183 HUMAN HEREDITARY CANCER WAS 1810 01:27:54,183 --> 01:27:57,253 BEING PHENOCOPIED BY 15% OF 1811 01:27:57,253 --> 01:27:58,554 INDIVIDUALS WHO DEVELOPED 1812 01:27:58,554 --> 01:27:59,655 COLORECTAL CANCER? 1813 01:27:59,655 --> 01:28:02,124 AND WE LOOKED FOR OTHER MEMBERS 1814 01:28:02,124 --> 01:28:07,029 OF THE DNA MISMATCH REPAIR. 1815 01:28:07,029 --> 01:28:15,605 WITHOUT SUCCESS. 1816 01:28:15,605 --> 01:28:18,174 WE LOOKED FOR SPLICE MUTATIONS. 1817 01:28:18,174 --> 01:28:19,542 THE ANSWER TURNED OUT TO BE IN 1818 01:28:19,542 --> 01:28:22,912 THE LAST PLACE WE LOOKED. 1819 01:28:22,912 --> 01:28:31,754 IT WAS IN THE COLON EPIGENOME. 1820 01:28:31,754 --> 01:28:32,054 N 1821 01:28:32,054 --> 01:28:35,257 IF THIS IS A SCHEMATIC SHOWING 1822 01:28:35,257 --> 01:28:38,594 THE LOCATION OF ONE OF GENES OF 1823 01:28:38,594 --> 01:28:40,763 THE DNA SPELL CHECKER HERE IN 1824 01:28:40,763 --> 01:28:41,697 THE WILD TYPE INDIVIDUALS YOU 1825 01:28:41,697 --> 01:28:46,602 SEE TWO GOOD COPIES OF GENES 1826 01:28:46,602 --> 01:28:49,672 BOTH BEING EXPRESSED. 1827 01:28:49,672 --> 01:28:52,341 AND IN LYNCH SYNDROME ONE 1828 01:28:52,341 --> 01:28:58,180 INHERITS A COPY OF THE HMLH1 AND 1829 01:28:58,180 --> 01:29:01,951 WHEN THE COPY IS LOST THE SPELL 1830 01:29:01,951 --> 01:29:06,522 CHECKER IS ACTIVATED AND NEOPLAY 1831 01:29:06,522 --> 01:29:13,195 SLA -- NEOPLASIA ACTIVATE AND IT 1832 01:29:13,195 --> 01:29:18,000 WAS COVERING UP THE PROMOTER OF 1833 01:29:18,000 --> 01:29:21,370 THE GENE SO IT COULDN'T BE 1834 01:29:21,370 --> 01:29:22,004 TURNED ON. 1835 01:29:22,004 --> 01:29:28,778 WHILE EPIGENETIC GENE SILENCING 1836 01:29:28,778 --> 01:29:30,012 CAN ACTIVATE GENES IN CANCER AND 1837 01:29:30,012 --> 01:29:33,449 IN 1988 THIS WAS ONE OF THE 1838 01:29:33,449 --> 01:29:38,287 FIRST SAMPLES OF SILENCING OF 1839 01:29:38,287 --> 01:29:40,690 THE GENE AND SO MUCH SURPRISED 1840 01:29:40,690 --> 01:29:43,993 BY THE OBSERVATION WE WERE 1841 01:29:43,993 --> 01:29:46,228 CONCERNED IT WAS A CORRELATIVE 1842 01:29:46,228 --> 01:29:47,930 AND MAY BE A CASE OF TRUE, TRUE 1843 01:29:47,930 --> 01:29:50,166 AND UNRELATED. 1844 01:29:50,166 --> 01:29:54,336 SO TO TRY TO GET FURTHER 1845 01:29:54,336 --> 01:29:56,906 EVIDENCE THE EPIGENETIC GENE 1846 01:29:56,906 --> 01:29:58,307 SILENCING COULD BE CAUSING 1847 01:29:58,307 --> 01:30:03,412 CANCER WE TURNED TO ANOTHER 1848 01:30:03,412 --> 01:30:05,481 HEREDITARY CANCER MODEL OF DI 1849 01:30:05,481 --> 01:30:10,119 DIFFUSED GASTRIC CANCER IS 1850 01:30:10,119 --> 01:30:13,723 CAUSED BY INHERITANCE OF THE 1851 01:30:13,723 --> 01:30:17,893 MUTANT FORM OF THE CDH1 GENE. 1852 01:30:17,893 --> 01:30:19,862 AND HERE IS A BIOPSY FROM THE 1853 01:30:19,862 --> 01:30:23,032 STOMACH OF AN INDIVIDUAL WHO HAS 1854 01:30:23,032 --> 01:30:26,068 INHERITED THE MUTATION. 1855 01:30:26,068 --> 01:30:27,703 IT'S BEING STAINED HERE IN THE 1856 01:30:27,703 --> 01:30:30,706 NORMAL PART AND YOU SEE THE 1857 01:30:30,706 --> 01:30:33,075 BROWN STAIN SHOWING THE PROTEIN 1858 01:30:33,075 --> 01:30:35,511 AND HERE IS THIS PATIENT'S 1859 01:30:35,511 --> 01:30:35,911 TUMOR. 1860 01:30:35,911 --> 01:30:38,080 THESE ARE HORRIBLE TUMORS. 1861 01:30:38,080 --> 01:30:43,052 YOU CAN SEE THEIR DIFFUSE CELLS 1862 01:30:43,052 --> 01:30:47,356 AND YOU CAN SEE IN THE TUMOR 1863 01:30:47,356 --> 01:30:51,994 THERE ARE TWO PRESERVED NORMAL 1864 01:30:51,994 --> 01:30:54,163 CYSTS THAT RETAINED EXPRESSION. 1865 01:30:54,163 --> 01:30:58,801 IN THE TUMORS IT'S BEEN 1866 01:30:58,801 --> 01:31:00,536 ACTIVATED AND WE ASKED HOW THAT 1867 01:31:00,536 --> 01:31:01,103 LAND. 1868 01:31:01,103 --> 01:31:02,972 IT HAPPENS BY THE DEVELOPMENT OF 1869 01:31:02,972 --> 01:31:06,308 A SECOND MUTATION THAT 1870 01:31:06,308 --> 01:31:08,144 INACTIVATES THE INHERITED WILD 1871 01:31:08,144 --> 01:31:11,280 TYPE ALLELE AND FOUND IT AGAIN 1872 01:31:11,280 --> 01:31:12,281 HAPPENS BY METHYLATION THAT 1873 01:31:12,281 --> 01:31:18,053 COVERS UP THE PROMOTER OF THE CD 1874 01:31:18,053 --> 01:31:25,861 H1 GENE ENCODING CADHERIN AND 1875 01:31:25,861 --> 01:31:26,962 IT'S THE SECOND HIT THAT GIVES 1876 01:31:26,962 --> 01:31:28,831 RISE TO THE CANCERS IN THESE 1877 01:31:28,831 --> 01:31:38,174 INDIVIDUALS WE NOW HAD THAT THE 1878 01:31:38,174 --> 01:31:40,276 METHYLATION WASN'T JUST 1879 01:31:40,276 --> 01:31:41,477 CORRELATED WITH CANCER BUT COULD 1880 01:31:41,477 --> 01:31:42,077 INITIATE IT. 1881 01:31:42,077 --> 01:31:45,514 IT LED TO STUDIES IN OUR 1882 01:31:45,514 --> 01:31:47,983 LABORATORY ASKING HOW COMMON IT 1883 01:31:47,983 --> 01:31:50,186 WAS AND FOUND THE METHYLATION 1884 01:31:50,186 --> 01:31:52,988 WAS HUGELY COMMON AND AFFECTED A 1885 01:31:52,988 --> 01:31:55,524 HUGE NUMBER OF GENES. 1886 01:31:55,524 --> 01:31:57,760 MANY WHICH DOESN'T SEEM TO BE 1887 01:31:57,760 --> 01:32:00,329 DIRECTLY INVOLVED IN 1888 01:32:00,329 --> 01:32:02,298 CARCINOGENESIS AND SERVED AS 1889 01:32:02,298 --> 01:32:02,898 BIOMARKERS USEFUL FOR EARLY 1890 01:32:02,898 --> 01:32:13,242 DETECTION OF CANCER. 1891 01:32:13,609 --> 01:32:16,445 WE TARGETED THE METHYLATION AND 1892 01:32:16,445 --> 01:32:19,381 HAVING A CLUSTER AS SHOWN IN THE 1893 01:32:19,381 --> 01:32:24,720 YELLOW BALLS OF IN THE FIRST 1894 01:32:24,720 --> 01:32:30,492 EXON AND FOUND IN COLON CANCER 1895 01:32:30,492 --> 01:32:31,927 80% OF THE TIME THEY BECAME 1896 01:32:31,927 --> 01:32:35,164 METHYLATED AND COULD EASILY 1897 01:32:35,164 --> 01:32:38,267 DETECT IT USING METHYLATION 1898 01:32:38,267 --> 01:32:40,069 SPECIFIC ASSAY. 1899 01:32:40,069 --> 01:32:42,171 WITH THE BIOMARKER IN HAND WE 1900 01:32:42,171 --> 01:32:44,506 WONDERED IF WE CAN USE THIS TO 1901 01:32:44,506 --> 01:32:46,041 DEVELOP A TEST FOR EARLY 1902 01:32:46,041 --> 01:32:47,943 DETECTION OF COLON CANCER. 1903 01:32:47,943 --> 01:32:50,179 THIS LED TO ONE OF THE FIRST 1904 01:32:50,179 --> 01:32:54,450 EXPERIMENTS. 1905 01:32:54,450 --> 01:32:57,620 OF TRYING TO DETECT METHYLATED 1906 01:32:57,620 --> 01:33:00,589 DNA AND HERE IS THE FIRST 1907 01:33:00,589 --> 01:33:02,458 EXPERIMENT PULLING DNA FROM A 1908 01:33:02,458 --> 01:33:04,460 STOOL SO THE COLON CANCER 1909 01:33:04,460 --> 01:33:07,863 PATIENTS YOU SEE THE DETECTION 1910 01:33:07,863 --> 01:33:11,100 OF THE METHYLATE D DNA IN THE 1911 01:33:11,100 --> 01:33:21,644 STOOLS OF COLON CANCER PATIENTS. 1912 01:33:31,453 --> 01:33:35,658 AND THERE WAS 84% SENSITIVITY TO 1913 01:33:35,658 --> 01:33:36,759 DETECT CURABLE CANCER STAGE 1 1914 01:33:36,759 --> 01:33:40,329 AND 2 CANCERS WITH SPECIFICITY 1915 01:33:40,329 --> 01:33:45,367 FROM 83% TO 90%. 1916 01:33:45,367 --> 01:33:49,805 WE BROUGHT THAT STUDY OUT IN 1917 01:33:49,805 --> 01:33:52,041 JNCI. 1918 01:33:52,041 --> 01:33:54,376 AND LAUNCHED THIS TEST 1919 01:33:54,376 --> 01:33:56,612 COMMERCIALLY IN COLLABORATION 1920 01:33:56,612 --> 01:34:04,420 WITH LAB CORP THE MARKETING ARM 1921 01:34:04,420 --> 01:34:07,323 AND ESTABLISHED YOU CAN DETECT 1922 01:34:07,323 --> 01:34:08,757 COLON CANCER THROUGH DE 1923 01:34:08,757 --> 01:34:11,660 METHYLATED DNA AND THIS IS THE 1924 01:34:11,660 --> 01:34:13,295 UNDERLYING TECHNOLOGY WHICH 1925 01:34:13,295 --> 01:34:17,533 TODAY DRIVES THE SECOND 1926 01:34:17,533 --> 01:34:21,370 IMPLEMENTATION OF COLOGUARD 1927 01:34:21,370 --> 01:34:22,738 STILL BEING OFFERED DIRECTLY BY 1928 01:34:22,738 --> 01:34:24,306 EXACT SCIENCES. 1929 01:34:24,306 --> 01:34:27,776 WITH THE UNDERSTANDING THAT 1930 01:34:27,776 --> 01:34:29,211 METHYLATED DNA WOULD BE A 1931 01:34:29,211 --> 01:34:30,779 BIOMARKER TO ENABLE EARLY 1932 01:34:30,779 --> 01:34:32,514 DETECTION OF G.I. CANCERS. 1933 01:34:32,514 --> 01:34:34,416 WE WONDERED IF THERE WERE OTHER 1934 01:34:34,416 --> 01:34:35,284 G.I. CANCERS TO TAKE ADVANTAGE 1935 01:34:35,284 --> 01:34:37,219 OF THE OBSERVATION. 1936 01:34:37,219 --> 01:34:40,723 AND ONE IN PARTICULAR WE WERE 1937 01:34:40,723 --> 01:34:44,827 INTERESTED UP WAS ESOPHAGEAL 1938 01:34:44,827 --> 01:34:49,832 CARCINOMA EAC BECAUSE IT WAS 1939 01:34:49,832 --> 01:34:54,436 SHINE ESOPHAGEAL CANCER CA 1940 01:34:54,436 --> 01:34:57,539 CARCINOMA WAS THE FASTEST 1941 01:34:57,539 --> 01:35:02,177 GROWING TUMOR AND YOU SEE THE IN 1942 01:35:02,177 --> 01:35:05,547 INCIDENTS OVER TIME. 1943 01:35:05,547 --> 01:35:10,119 IT WAS SELDOM DETECTED EARLY AND 1944 01:35:10,119 --> 01:35:11,854 THERE WAS DIFFICULT IN 1945 01:35:11,854 --> 01:35:14,023 SWALLOWING AND SURVIVAL WITH THE 1946 01:35:14,023 --> 01:35:18,527 CANCER IS ABYSMAL LESS THAN 20% 1947 01:35:18,527 --> 01:35:20,129 ON PAR WITH PANCREAS CANCER. 1948 01:35:20,129 --> 01:35:23,999 WE WERE AWARE THERE WAS AN 1949 01:35:23,999 --> 01:35:24,299 OPPORTUNITY. 1950 01:35:24,299 --> 01:35:28,871 AS COLORECTAL CANCERS HAVE THIS 1951 01:35:28,871 --> 01:35:34,176 AND THERE'S A PRECURSOR. 1952 01:35:34,176 --> 01:35:37,312 THERE'S A LESION CALLED 1953 01:35:37,312 --> 01:35:38,714 BARRETT'S ESOPHAGUS AND THOUGHT 1954 01:35:38,714 --> 01:35:45,054 TO ARISE IN PATIENTS WITH 1955 01:35:45,054 --> 01:35:46,188 EPISODIC HEART BURN AND 1956 01:35:46,188 --> 01:35:49,625 RECOGNIZING ALLOWS AN 1957 01:35:49,625 --> 01:35:54,430 ENDOSCOPIST TO ABLATE THE 1958 01:35:54,430 --> 01:35:57,533 DISEASE AND DETER THE PROGRESS 1959 01:35:57,533 --> 01:35:58,400 OF DISEASE. 1960 01:35:58,400 --> 01:36:00,869 AND HOW WITH WE GOING TO SAMPLE 1961 01:36:00,869 --> 01:36:04,473 THE ESOPHAGUS? 1962 01:36:04,473 --> 01:36:09,144 TO DO THAT WE DEVELOPED A FUN 1963 01:36:09,144 --> 01:36:13,649 LITTLE DEVICE NOW KNOWN AS 1964 01:36:13,649 --> 01:36:14,149 ESOCHECK. 1965 01:36:14,149 --> 01:36:24,693 A CAPSULE THE SIZE OF A VITAMIN 1966 01:36:26,228 --> 01:36:30,165 AND IT WOULD BALLOON AND THE 1967 01:36:30,165 --> 01:36:32,868 BALLOON COULD BE POPPED OUT 1968 01:36:32,868 --> 01:36:35,137 WHERE THE ESOPHAGUS ARISES AND 1969 01:36:35,137 --> 01:36:39,641 THE AIR CAN BE WITHDRAWN AND 1970 01:36:39,641 --> 01:36:41,376 SHRINK THE BALLOON BACK DOWN TO 1971 01:36:41,376 --> 01:36:47,416 THE SIZE OF A VITAMIN PILL AND 1972 01:36:47,416 --> 01:36:48,617 PAIRED IT BACK AND DID A 1973 01:36:48,617 --> 01:36:50,152 CLINICAL TRIAL. 1974 01:36:50,152 --> 01:36:56,024 THIS WAS BROUGHT OUT IN SCIENCE 1975 01:36:56,024 --> 01:36:59,962 TRANSLATIONAL MEDICINE AND THE 1976 01:36:59,962 --> 01:37:04,299 BALLOON AND METHYLATED DNA WAS 1977 01:37:04,299 --> 01:37:08,036 SENSITIVE FOR FINDING BARRETT'S 1978 01:37:08,036 --> 01:37:09,538 ESOPHAGUS IN INDIVIDUALS WITH 1979 01:37:09,538 --> 01:37:13,208 LONG STANDING HEART BURN. 1980 01:37:13,208 --> 01:37:16,044 THE ABILITY TO IDENTIFY WAS 1981 01:37:16,044 --> 01:37:18,780 RECOGNIZED AS SPECIALLY AN 1982 01:37:18,780 --> 01:37:20,582 IMPACTFUL TECHNOLOGY AND THE 1983 01:37:20,582 --> 01:37:22,951 YEAR THE PAPER WAS PUBLISHED WAS 1984 01:37:22,951 --> 01:37:25,154 HIGHLIGHTED IN THE NCI 1985 01:37:25,154 --> 01:37:27,756 DIRECTOR'S ANNUAL REPORT TO 1986 01:37:27,756 --> 01:37:31,193 CONGRESS WITH THIS NICE INFO 1987 01:37:31,193 --> 01:37:31,426 GRAPHIC. 1988 01:37:31,426 --> 01:37:40,536 SO WHAT'S HAPPENED IS WE WERE 1989 01:37:40,536 --> 01:37:44,173 ABLE IT BRING IT TO LICENSE. 1990 01:37:44,173 --> 01:37:45,908 IN 2009 THE BALLOON DEVICE 1991 01:37:45,908 --> 01:37:49,678 RECEIVED FDA APPROVAL AND THE 1992 01:37:49,678 --> 01:37:51,413 METHYLATED DNA PANEL RECEIVED 1993 01:37:51,413 --> 01:37:53,282 BREAKTHROUGH DEVICE DESIGNATION 1994 01:37:53,282 --> 01:37:55,817 AND IN 2022 THE COMBINATION OF 1995 01:37:55,817 --> 01:38:04,626 WHAT IS NOW THE ESO CHECK DEVICE 1996 01:38:04,626 --> 01:38:07,863 WERE INCORPORATED INTO THE 1997 01:38:07,863 --> 01:38:10,299 SCREENING RECOMMENDATIONS INTO 1998 01:38:10,299 --> 01:38:14,970 THE GASTROENTEROLOGICAL 1999 01:38:14,970 --> 01:38:15,270 ASSOCIATION. 2000 01:38:15,270 --> 01:38:22,177 THIS IS NOW AN EMERGING STANDARD 2001 01:38:22,177 --> 01:38:25,113 APPROACH FOR SCREENING AND 2002 01:38:25,113 --> 01:38:27,049 PREVENTION OF ESOPHAGEAL 2003 01:38:27,049 --> 01:38:27,316 CARCINOMA. 2004 01:38:27,316 --> 01:38:30,152 SINCE OUR ORIGINAL PAPER IN 2005 01:38:30,152 --> 01:38:34,156 SCIENCE TRANSLATIONAL MEDICINE 2006 01:38:34,156 --> 01:38:35,824 FOLLOW VALIDATION STUDIES. 2007 01:38:35,824 --> 01:38:37,826 AND THOSE ESTABLISHED THE 2008 01:38:37,826 --> 01:38:39,061 POSITIVE PREDICTIVE VALUE OF THE 2009 01:38:39,061 --> 01:38:42,497 TECHNOLOGY IS ABOUT 30% WHICH IS 2010 01:38:42,497 --> 01:38:43,899 BETTER THAN ALMOST ANY OTHER 2011 01:38:43,899 --> 01:38:50,005 SCREENING ASSAY IN CLINICAL USE. 2012 01:38:50,005 --> 01:38:52,174 SO, STARTING WITH STUDIES OF 2013 01:38:52,174 --> 01:38:54,343 LYNCH SYNDROME WE WERE ABLE TO 2014 01:38:54,343 --> 01:38:56,678 FROM EARLY ONSET CANCER SYNDROME 2015 01:38:56,678 --> 01:39:00,382 OF YOUNG INDIVIDUALS IDENTIFY 2016 01:39:00,382 --> 01:39:02,150 GENETIC PATHWAY THAT LED TO 2017 01:39:02,150 --> 01:39:05,454 EARLY ONSET COLON CANCER. 2018 01:39:05,454 --> 01:39:07,489 STUDIES OF THAT PATHWAY 2019 01:39:07,489 --> 01:39:10,826 INTERROGATION OF THE PATHWAY LED 2020 01:39:10,826 --> 01:39:14,229 TO THE IDENTIFICATION OF 2021 01:39:14,229 --> 01:39:16,331 PROSTAGLANDIN HYDROGENASE FOR 2022 01:39:16,331 --> 01:39:19,368 TISSUE REGENERATION AND GIVEN 2023 01:39:19,368 --> 01:39:24,706 RISE TO A NEW CANDIDATE DRUG FOR 2024 01:39:24,706 --> 01:39:25,674 TREATING ULCERATIVE COLITIS AND 2025 01:39:25,674 --> 01:39:29,745 OTHER DISEASES AND LED TO THE 2026 01:39:29,745 --> 01:39:33,048 DNA METHYLATION AS A WIDESPREAD 2027 01:39:33,048 --> 01:39:34,149 PHENOMENON IN CANCER. 2028 01:39:34,149 --> 01:39:38,520 AND ALLOWED US TO GIVE RISE TO 2029 01:39:38,520 --> 01:39:42,858 FIRST THE USE OF METHYLATED DNA 2030 01:39:42,858 --> 01:39:45,827 IN STOOL AS A BIOMARKER FOR 2031 01:39:45,827 --> 01:39:48,764 EARLY CANCER DETECTION AND 2032 01:39:48,764 --> 01:39:51,466 METHYLATED DNA EFFORTING IN 2033 01:39:51,466 --> 01:39:52,434 ESOPHAGEAL SAMPLES FOR EARLY 2034 01:39:52,434 --> 01:39:58,173 DETECTION OF DISEASE. 2035 01:39:58,173 --> 01:39:59,608 SO THIS WAS THE WONDERFUL 2036 01:39:59,608 --> 01:40:02,244 WONDERFUL TEAM OF INDIVIDUALS 2037 01:40:02,244 --> 01:40:06,181 WHO PARTNERED TOGETHER IN THE 2038 01:40:06,181 --> 01:40:10,585 PGDH STUDIES. 2039 01:40:10,585 --> 01:40:13,822 AND HERE THE TEAM THAT PARTNERED 2040 01:40:13,822 --> 01:40:16,692 ON THE STUDIES ON THE ESOPHAGUS 2041 01:40:16,692 --> 01:40:20,162 AND WANT TO ACKNOWLEDGE THE 2042 01:40:20,162 --> 01:40:24,266 FUNDING SOURCES QUITE 2043 01:40:24,266 --> 01:40:29,171 PROMINENTLY FROM THE NIH AND 2044 01:40:29,171 --> 01:40:33,141 R-35 AND BETTER NET PROGRAM AS 2045 01:40:33,141 --> 01:40:37,112 WELL AS INCUBATOR AWARDS THAT WE 2046 01:40:37,112 --> 01:40:40,649 RECEIVED TO DEVELOP THESE 2047 01:40:40,649 --> 01:40:48,156 TECHNOLOGIES INCLUDING FROM THE 2048 01:40:48,156 --> 01:40:52,561 HARINGTON INSTITUTE AND KECK 2049 01:40:52,561 --> 01:40:55,263 SCHOOL OF MEDICINE AND THE 2050 01:40:55,263 --> 01:41:02,704 SUPPORT I RECEIVED AS A HOWARD 2051 01:41:02,704 --> 01:41:03,772 HUGHES INVESTIGATOR. 2052 01:41:03,772 --> 01:41:05,307 THAT BRINGS ME TO THE CONCLUSION 2053 01:41:05,307 --> 01:41:06,541 OF THE WORK AND I'M HAPPY TO 2054 01:41:06,541 --> 01:41:16,485 PAUSE AND SEE IF I CAN RETURN 2055 01:41:16,485 --> 01:41:18,186 THE CONTROL OF THE SYMPOSIUM 2056 01:41:18,186 --> 01:41:23,425 BACK TO WIN. 2057 01:41:23,425 --> 01:41:25,293 >> YOU'RE BACK. 2058 01:41:25,293 --> 01:41:29,264 DR. ARIAS, CAN YOU UNMUTE 2059 01:41:29,264 --> 01:41:30,198 YOURSELF? 2060 01:41:30,198 --> 01:41:32,801 WE HAD TO MUTE YOU. 2061 01:41:32,801 --> 01:41:35,170 IN MUTE YOURSELF, DR. ARIAS, UP 2062 01:41:35,170 --> 01:41:38,206 IN THE CORNER THERE. 2063 01:41:38,206 --> 01:41:38,273 2064 01:41:47,949 --> 01:41:48,617 >> THANK YOU VERY MUCH. 2065 01:41:48,617 --> 01:41:52,154 WE'VE HAD A SERIES OF QUESTIONS 2066 01:41:52,154 --> 01:41:54,790 AND THANK YOU BOTH FOR VERY 2067 01:41:54,790 --> 01:41:58,193 PROVOCATIVE AND INTERESTING 2068 01:41:58,193 --> 01:41:59,661 PRESENTATIONS. 2069 01:41:59,661 --> 01:42:02,431 SO, LET ME BEGIN ONE A QUESTION 2070 01:42:02,431 --> 01:42:06,735 WE HAD SEVERAL TIMES. 2071 01:42:06,735 --> 01:42:13,308 AND THAT IS WHETHER COLON CANCER 2072 01:42:13,308 --> 01:42:16,411 IN PARTICULAR IS ALWAYS RELATED 2073 01:42:16,411 --> 01:42:22,350 TO THE FORMATION OF A POLYP OR 2074 01:42:22,350 --> 01:42:26,188 ARE THERE OTHER FORMS THAT FOR 2075 01:42:26,188 --> 01:42:29,291 EXAMPLE MIGHT BEGIN WITH AN 2076 01:42:29,291 --> 01:42:31,059 ULCERATIVE PHENOTYPE. 2077 01:42:31,059 --> 01:42:32,627 IS A POLYP AN ESSENTIAL PART IN 2078 01:42:32,627 --> 01:42:36,731 THE DEVELOPMENT OF SPORADIC -- 2079 01:42:36,731 --> 01:42:38,600 >> THERE ARE NUANCES TO THAT 2080 01:42:38,600 --> 01:42:44,105 QUESTION. 2081 01:42:44,105 --> 01:42:48,743 SO THE CLASSIC TUBULAR ADENOMA 2082 01:42:48,743 --> 01:42:50,178 INITIATED BY THE PATIENTS IS 2083 01:42:50,178 --> 01:42:56,785 VERY MUCH A FEATURE OF THE GREAT 2084 01:42:56,785 --> 01:43:00,555 PROBABLY ALMOST ALL CANCERS THAT 2085 01:43:00,555 --> 01:43:02,491 ARISE IN THE RECTUM AND 2086 01:43:02,491 --> 01:43:07,863 DESCENDING AND TRANSVERSE COLON. 2087 01:43:07,863 --> 01:43:09,798 IN THE DESCENDING COLON THERE'S 2088 01:43:09,798 --> 01:43:14,269 A FEATURE OF SERRATED ADENOMAS 2089 01:43:14,269 --> 01:43:16,671 AND THESE ARE FLAT LESIONS AND 2090 01:43:16,671 --> 01:43:18,773 INDEED FOR MANY YEARS THEY WERE 2091 01:43:18,773 --> 01:43:23,311 NOT APPRECIATED ENDOSCOPICALLY 2092 01:43:23,311 --> 01:43:26,181 BECAUSE THEY DON'T HAVE THAT 2093 01:43:26,181 --> 01:43:27,916 TYPICAL MUSHROOM APPEARANCE 2094 01:43:27,916 --> 01:43:31,786 THROUGH A COLONOSCOPE. 2095 01:43:31,786 --> 01:43:32,954 THERE'S MORE CHANGES IN THE 2096 01:43:32,954 --> 01:43:41,696 TEXTURE OF THE COATING. 2097 01:43:41,696 --> 01:43:44,933 NONETHELESS, WHEN THEY'RE 2098 01:43:44,933 --> 01:43:47,035 BIOPSIED THEY ARE CALLED 2099 01:43:47,035 --> 01:43:51,573 SERRATED ADENOMAS. 2100 01:43:51,573 --> 01:43:53,508 IN CERTAIN DISEASE SETTINGS SUCH 2101 01:43:53,508 --> 01:43:57,479 AS ULCERATIVE COLITIS ONE CAN 2102 01:43:57,479 --> 01:44:01,416 FIND THE EMERGENCE OF LESIONS 2103 01:44:01,416 --> 01:44:05,320 THAT HAVE THIS PLASTIC HISTOLOGY 2104 01:44:05,320 --> 01:44:09,457 THAT APPEAR TO BE IN A DIRECTLY 2105 01:44:09,457 --> 01:44:13,361 DEVELOPED DYSPLASIAS IN THE 2106 01:44:13,361 --> 01:44:17,799 COLONIC MUCOSA WITHOUT THE 2107 01:44:17,799 --> 01:44:19,801 CLASSIC EITHER TUBULAR OR 2108 01:44:19,801 --> 01:44:23,371 SERRATED ADENOMA. 2109 01:44:23,371 --> 01:44:26,241 INDEED THESE ARE HARD TO DETECT 2110 01:44:26,241 --> 01:44:30,278 SCOPICALLY AND ONE MUCH THE 2111 01:44:30,278 --> 01:44:34,215 REASONS INDIVIDUALS WITH 2112 01:44:34,215 --> 01:44:36,885 ULCERATIVE COLITIS ARE SURVEYED 2113 01:44:36,885 --> 01:44:39,588 WITH BIOPSIES TO SEE WHERE THE 2114 01:44:39,588 --> 01:44:41,790 LESIONS ARE ARRIVING. 2115 01:44:41,790 --> 01:44:44,960 CLOSELY RELATED TO THIS ARE 2116 01:44:44,960 --> 01:44:50,665 POTENTIALLY A RARER FORM OF 2117 01:44:50,665 --> 01:44:52,934 COLON CANCER RESPONSIBLE FOR 2118 01:44:52,934 --> 01:44:58,206 SINGLE DIGIT PERCENTAGES OF 2119 01:44:58,206 --> 01:45:00,642 COLORECTAL CANCER AND SIGNET 2120 01:45:00,642 --> 01:45:04,879 RATE COLON CANCER IS ENRICHED IN 2121 01:45:04,879 --> 01:45:06,881 THE EARLY ONSET COLON CANCERS. 2122 01:45:06,881 --> 01:45:10,452 IT'S ENRICHED IN INDIVIDUALS. 2123 01:45:10,452 --> 01:45:15,657 I WOULD SAY THE GENESIS OF 2124 01:45:15,657 --> 01:45:18,627 SIGNET COLON CANCER IS LESS 2125 01:45:18,627 --> 01:45:20,061 SIGNIFICANT AND THE PRESENCE OF 2126 01:45:20,061 --> 01:45:23,231 THE GENE THOUGH PRESENT IS LESS 2127 01:45:23,231 --> 01:45:27,636 COMMON IN SIGNET COLON CANCERS 2128 01:45:27,636 --> 01:45:30,672 THAN CLASSIC SPORADIC COLON 2129 01:45:30,672 --> 01:45:34,142 CANCER. 2130 01:45:34,142 --> 01:45:38,213 TO FIRST APPROVXIMATION TO DO 2131 01:45:38,213 --> 01:45:40,215 THEY ALL ORIGINATE IN POLYPS, 2132 01:45:40,215 --> 01:45:41,583 THEY ARE DO. 2133 01:45:41,583 --> 01:45:44,886 TO A MORE GRAND RESPONSE THERE 2134 01:45:44,886 --> 01:45:48,723 ARE SOME SPECIFIC EXCEPTIONS TO 2135 01:45:48,723 --> 01:45:52,927 THAT GENERALIZATION INCLUDING 2136 01:45:52,927 --> 01:45:55,764 COLORECTAL CANCERS THAT ARISE IN 2137 01:45:55,764 --> 01:45:58,299 THE SETTING OF ULCERATIVE 2138 01:45:58,299 --> 01:46:06,141 COLITIS AND THEY DO TEND TO 2139 01:46:06,141 --> 01:46:07,108 ARISE IN A YOUNGER POPULATION 2140 01:46:07,108 --> 01:46:10,745 AND INDEED THIS IS A DISEASE 2141 01:46:10,745 --> 01:46:13,348 THAT'S BEEN OF INTEREST FOR 2142 01:46:13,348 --> 01:46:15,617 LABORATORY AND WE'VE BEEN 2143 01:46:15,617 --> 01:46:18,086 SUPPORTED BY A CROWD SOURCE 2144 01:46:18,086 --> 01:46:20,789 CONSORTIUM OF FAMILIES WHO HAVE 2145 01:46:20,789 --> 01:46:23,091 HAD PATIENTS WITH THESE DISEASE 2146 01:46:23,091 --> 01:46:26,194 WITH SIGNIFICANT COLON CANCER 2147 01:46:26,194 --> 01:46:29,564 AND THE PATIENTS AS YOUNG AS 14 2148 01:46:29,564 --> 01:46:31,499 YEARS OLD SO YOU SEE SHOCKINGLY 2149 01:46:31,499 --> 01:46:32,801 YOUNG INDIVIDUALS WITH THIS 2150 01:46:32,801 --> 01:46:34,936 DISEASE. 2151 01:46:34,936 --> 01:46:35,570 >> THANK YOU. 2152 01:46:35,570 --> 01:46:38,840 SO REBECCA, SEVERAL PEOPLE HAVE 2153 01:46:38,840 --> 01:46:41,810 BEEN CURIOUS ABOUT WHAT DO YOU 2154 01:46:41,810 --> 01:46:45,647 THINK HAPPENED IN 1990 AND HOW 2155 01:46:45,647 --> 01:46:50,385 DOES AN EPIDEMIOLOGIST GO ABOUT 2156 01:46:50,385 --> 01:46:58,760 TRYING TO SORT OUT POSSIBLE 2157 01:46:58,760 --> 01:47:09,170 MECHANISMS TO BE TESTED? 2158 01:47:21,449 --> 01:47:23,485 >> IT'S NOT SOMETHING THAT 2159 01:47:23,485 --> 01:47:25,053 CHANGED IN THE 1990s BUT THE 2160 01:47:25,053 --> 01:47:26,154 MIDDLE OF THE 20th CENTURY. 2161 01:47:26,154 --> 01:47:27,088 THAT'S WHEN WE START THE TO SEE 2162 01:47:27,088 --> 01:47:32,393 THE ELEVATED RISK. 2163 01:47:32,393 --> 01:47:33,194 AND EVEN EARLIER FOR RECTAL 2164 01:47:33,194 --> 01:47:34,362 CANCER. 2165 01:47:34,362 --> 01:47:39,367 I MEAN, IF WE THINK ABOUT -- 2166 01:47:39,367 --> 01:47:41,069 THINK ABOUT WHEN I WAS A KID AND 2167 01:47:41,069 --> 01:47:43,338 WHAT I WAS EATING FOR DINNER 2168 01:47:43,338 --> 01:47:44,572 VERSUS WHAT MOST PEOPLE ARE 2169 01:47:44,572 --> 01:47:47,108 EATING FOR DINNER NOW, OUR FOOD 2170 01:47:47,108 --> 01:47:50,478 SUPPLY HAS CHANGED TREMENDOUSLY. 2171 01:47:50,478 --> 01:47:52,113 MY GUESS IS IT WILL HAVE 2172 01:47:52,113 --> 01:47:56,818 SOMETHING TO DO WITH SOMETHING 2173 01:47:56,818 --> 01:47:57,152 TH 2174 01:47:57,152 --> 01:47:58,219 THAT'S BEING CONSUMED BECAUSE 2175 01:47:58,219 --> 01:48:00,588 THAT'S WHAT YOU WOULD THINK OF 2176 01:48:00,588 --> 01:48:03,758 WHEN YOU THINK OF THE GUT AND 2177 01:48:03,758 --> 01:48:05,627 INFLUENCES THERE. 2178 01:48:05,627 --> 01:48:07,595 I THINK IT'S GOING TO REQUIRE A 2179 01:48:07,595 --> 01:48:09,330 PROSPECTIVE COHORT SO PEOPLE CAN 2180 01:48:09,330 --> 01:48:13,868 BE STUDIED AND FOLLOWED OVER 2181 01:48:13,868 --> 01:48:14,169 TIME. 2182 01:48:14,169 --> 01:48:16,237 UNFORTUNATELY, MOST COHORTS ARE 2183 01:48:16,237 --> 01:48:17,272 OLDER ADULTS. 2184 01:48:17,272 --> 01:48:20,975 SO I KNOW THAT THERE IS THERE 2185 01:48:20,975 --> 01:48:24,012 ARE NEWER COHORTS JUST BEING 2186 01:48:24,012 --> 01:48:25,280 STARTED BUT UNFORTUNATELY THAT 2187 01:48:25,280 --> 01:48:29,150 IS GOING TO TAKE A VERY LONG 2188 01:48:29,150 --> 01:48:39,260 TIME. 2189 01:48:43,431 --> 01:48:44,899 >> WE'VE IDENTIFIED SOMETHING 2190 01:48:44,899 --> 01:48:46,167 BUT SO FAR THERE ISN'T 2191 01:48:46,167 --> 01:48:49,337 ANYTHING -- I THINK THERE'S SO 2192 01:48:49,337 --> 01:48:50,605 MANY MIXED EXPOSURES. 2193 01:48:50,605 --> 01:48:52,607 THERE'S SO MUCH GOING ON IN THE 2194 01:48:52,607 --> 01:48:52,907 ENVIRONMENT. 2195 01:48:52,907 --> 01:48:57,512 WHETHER IT'S PESTICIDES OR 2196 01:48:57,512 --> 01:49:01,182 CHANGES IN FOOD AND THE 2197 01:49:01,182 --> 01:49:04,185 MICROPLASTIC EXPOSURES. 2198 01:49:04,185 --> 01:49:05,353 AUTOPSY STUDIES ARE SHOWING 2199 01:49:05,353 --> 01:49:09,624 MICROPLASTICS IN THE BRAIN 2200 01:49:09,624 --> 01:49:12,560 BREAKING THROUGH THE BLOOD BRAIN 2201 01:49:12,560 --> 01:49:12,794 BARRIER. 2202 01:49:12,794 --> 01:49:17,398 IT'S OVERWHELMING TO THINK. 2203 01:49:17,398 --> 01:49:19,734 >> I EXPECT PART OF THE 2204 01:49:19,734 --> 01:49:21,936 CHALLENGE IS GOING TO BE VERY 2205 01:49:21,936 --> 01:49:23,571 OFTEN WHAT ONE IS LOOKING AT IS 2206 01:49:23,571 --> 01:49:26,774 THE INTERACTION OF AN 2207 01:49:26,774 --> 01:49:28,142 ENVIRONMENTAL EXPOSURE AT A 2208 01:49:28,142 --> 01:49:30,812 GENETIC SUSCEPTIBILITY. 2209 01:49:30,812 --> 01:49:33,281 IF YOU LOOK AT THE HISTORY OF 2210 01:49:33,281 --> 01:49:37,886 SYNDROME, IT WAS ACTUALLY FIRST 2211 01:49:37,886 --> 01:49:42,190 DESCRIBED AT THE UNIVERSITY OF 2212 01:49:42,190 --> 01:49:45,293 MICHIGAN AT THE TURN OF THE 2213 01:49:45,293 --> 01:49:48,663 CENTURY OVER A CENTURY AGO AND 2214 01:49:48,663 --> 01:49:57,071 THERE WAS A SEAMSTRESS HE 2215 01:49:57,071 --> 01:50:01,109 CHASTISED AND SHE DIED YOUNG AND 2216 01:50:01,109 --> 01:50:04,679 WHAT HE DESCRIBED WAS GASTRIC 2217 01:50:04,679 --> 01:50:04,913 CANCER. 2218 01:50:04,913 --> 01:50:09,651 AND HE DESCRIBED A KINDRED THE 2219 01:50:09,651 --> 01:50:11,352 SEAMSTRESS'S KINDRED OF 2220 01:50:11,352 --> 01:50:11,753 HEREDITARY CANCER. 2221 01:50:11,753 --> 01:50:14,522 THE SAMPLED WERE PRESERVED AT 2222 01:50:14,522 --> 01:50:16,824 THE UNIVERSITY OF MICHIGAN AND 2223 01:50:16,824 --> 01:50:24,933 THE SEAMSTRESS HAD LYNCH 2224 01:50:24,933 --> 01:50:28,670 SYNDROME AND THEY DEVELOPED 2225 01:50:28,670 --> 01:50:31,306 GASTRIC NOT COLON CANCER. 2226 01:50:31,306 --> 01:50:34,676 CLEARLY A GENETIC SUSCEPTIBILITY 2227 01:50:34,676 --> 01:50:45,186 IN THE EXPRESSION AND AT THE 2228 01:50:52,860 --> 01:50:56,631 TURN OF THE 20th CENTURY GASTRIC 2229 01:50:56,631 --> 01:51:01,069 CANCER WAS COMMON NOT COLON AND 2230 01:51:01,069 --> 01:51:04,605 THINGS ARE ASSOCIATED WITH 2231 01:51:04,605 --> 01:51:10,878 GASTRIC CANCER. 2232 01:51:10,878 --> 01:51:13,381 THERE MAY BE A UBIQUITOUS 2233 01:51:13,381 --> 01:51:15,483 ENVIRONMENTAL EXPOSURE FOR THE 2234 01:51:15,483 --> 01:51:18,286 ONSET OF EARLY AGE COLORECTAL 2235 01:51:18,286 --> 01:51:21,255 CANCER NOW BUT IT'S NOT 100% OF 2236 01:51:21,255 --> 01:51:23,191 YOUNG PEOPLE GETTING COLON 2237 01:51:23,191 --> 01:51:23,825 CANCER. 2238 01:51:23,825 --> 01:51:25,226 IT'S A SMALL SUBSET. 2239 01:51:25,226 --> 01:51:28,062 MY GUESS IS THE SMALL SUBSET HAS 2240 01:51:28,062 --> 01:51:29,430 A PARTICULAR GENETIC 2241 01:51:29,430 --> 01:51:30,932 SUSCEPTIBILITY AND WHATEVER THAT 2242 01:51:30,932 --> 01:51:31,833 ENVIRONMENTAL EXPOSURE IS. 2243 01:51:31,833 --> 01:51:32,633 THE SAME THING IS TRUE OF 2244 01:51:32,633 --> 01:51:42,777 SMOKERS. 2245 01:51:43,611 --> 01:51:46,080 IT WAS UBIQUITOUS AND ALL THE 2246 01:51:46,080 --> 01:51:52,453 G.I.'S WERE GIVING CIGARETTES 2247 01:51:52,453 --> 01:52:02,530 A 2248 01:52:05,266 --> 01:52:10,671 AND ABOUT WHAT UNDER LIES THOSE 2249 01:52:10,671 --> 01:52:14,042 WHO SMOKED AND DEVELOPED LUNG 2250 01:52:14,042 --> 01:52:15,543 CANCER THOSE THAT LIVED TO A 2251 01:52:15,543 --> 01:52:17,879 RIPE OLD AGE. 2252 01:52:17,879 --> 01:52:19,647 THE EPIDEMIOLOGY WILL NEED TO BE 2253 01:52:19,647 --> 01:52:22,750 INFORMED BY SOME SHREWD GUESSES 2254 01:52:22,750 --> 01:52:23,985 TO WHAT THE SUSCEPTIBLE 2255 01:52:23,985 --> 01:52:32,994 POPULATION LOOKS LIKE. 2256 01:52:32,994 --> 01:52:37,565 >> ARE THERE OTHER STUDIES ALONG 2257 01:52:37,565 --> 01:52:39,600 BACTERIAL FREE MICE THAT ALSO 2258 01:52:39,600 --> 01:52:44,205 HAVE MUTATIONS IN THE TGF BETA 2259 01:52:44,205 --> 01:52:51,512 SYSTEM THAT MAY LEND SOME CLUES 2260 01:52:51,512 --> 01:52:52,680 AS TO THE ROLE OF THE MICROBIOME 2261 01:52:52,680 --> 01:52:54,315 AND THE DEVELOPMENT OF CANCER. 2262 01:52:54,315 --> 01:52:58,886 >> THE MICROBIOME PLAYS A 2263 01:52:58,886 --> 01:53:00,121 CRUCIAL ROLE IN VIRTUALLY EVERY 2264 01:53:00,121 --> 01:53:00,588 MOUSE MODEL. 2265 01:53:00,588 --> 01:53:08,129 THE DSS MODEL I PRESENTED IS A 2266 01:53:08,129 --> 01:53:08,863 MICROBIOME DEPENDENT MODEL 2267 01:53:08,863 --> 01:53:12,400 RAISED IN A GERM-FREE 2268 01:53:12,400 --> 01:53:13,067 ENVIRONMENT. 2269 01:53:13,067 --> 01:53:23,611 DON'T DEVELOP AND SO THERE HAVE 2270 01:53:50,605 --> 01:53:55,510 BEEN A COUPLE OF SPECIES BUGS 2271 01:53:55,510 --> 01:53:59,413 AND REASONABLY CONVINCINGLY 2272 01:53:59,413 --> 01:54:03,017 ASSOCIATED WITH COLON 2273 01:54:03,017 --> 01:54:03,384 CARCINOGENESIS. 2274 01:54:03,384 --> 01:54:06,187 THERE ARE STRAINS OF E. COLI 2275 01:54:06,187 --> 01:54:13,261 THAT PRODUCE COLOBACTINS AND CAN 2276 01:54:13,261 --> 01:54:18,199 DAMAGE DNA AND THE MUTATIONAL 2277 01:54:18,199 --> 01:54:20,401 SIGNATURE OF BACTINS ARE 2278 01:54:20,401 --> 01:54:22,036 DISTINCT ENOUGH TO BE DETECTED 2279 01:54:22,036 --> 01:54:23,638 IN COLON CANCERS BUT WE'RE 2280 01:54:23,638 --> 01:54:26,574 TALKING A SMALL SLICE OF PIE. 2281 01:54:26,574 --> 01:54:30,211 THERE'S BEEN STUDIES WITH 2282 01:54:30,211 --> 01:54:32,013 FUSERBACTERIUM ASSOCIATED AS 2283 01:54:32,013 --> 01:54:33,681 BEING INCREASED IN THE 2284 01:54:33,681 --> 01:54:37,718 MICROBIOME OF HUMANS WITH COLON 2285 01:54:37,718 --> 01:54:39,787 CANCER AND TRANSPLANTED INTO 2286 01:54:39,787 --> 01:54:41,289 MICE AND CAN INCREASE THE 2287 01:54:41,289 --> 01:54:42,056 INCIDENTS OF TUMORS IN MOUSE 2288 01:54:42,056 --> 01:54:50,865 MODELS. 2289 01:54:50,865 --> 01:54:54,202 THAT'S MORE OF A CORRELATIVE 2290 01:54:54,202 --> 01:54:58,206 DEVELOPMENT WHEN THERE'S NOT A 2291 01:54:58,206 --> 01:54:59,340 MUTATIONAL FINGERPRINT SAYING 2292 01:54:59,340 --> 01:55:01,008 IT'S NOT JUST THEIR FELLOW 2293 01:55:01,008 --> 01:55:01,676 TRAVELLERS THAT LIKE TO GROW ON 2294 01:55:01,676 --> 01:55:07,848 TUMORS. 2295 01:55:07,848 --> 01:55:09,984 WHAT WE'RE SAYING IS WE KNOW THE 2296 01:55:09,984 --> 01:55:12,086 MICROBIOME MATTERS AND HOW IT 2297 01:55:12,086 --> 01:55:12,486 WORKS. 2298 01:55:12,486 --> 01:55:17,792 >> SO REBECCA, IN YOUR TALK YOU 2299 01:55:17,792 --> 01:55:25,166 MENTIONED AS POSSIBLE FACTORS IN 2300 01:55:25,166 --> 01:55:29,437 THE DEVELOPMENT OF COLORECTAL 2301 01:55:29,437 --> 01:55:35,443 CANCER AND THE EFFECT OF WATER 2302 01:55:35,443 --> 01:55:36,377 CONTAMINATION AND ALL SORTS OF 2303 01:55:36,377 --> 01:55:38,212 THINGS AND YOU MADE A COMMENT 2304 01:55:38,212 --> 01:55:40,214 SHOWING DIFFERENT ARTICLES 2305 01:55:40,214 --> 01:55:41,515 PUBLISHED BUT YOU SAID THAT NONE 2306 01:55:41,515 --> 01:55:43,417 OF THESE ARE DEFINITIVE. 2307 01:55:43,417 --> 01:55:46,921 SO WE HAVE AN INTERESTING 2308 01:55:46,921 --> 01:55:49,290 QUESTION, THAT IS WHAT 2309 01:55:49,290 --> 01:55:52,793 CONSTITUTES A DEFINITIVE 2310 01:55:52,793 --> 01:55:54,362 EPIDEMIOLOGIC STUDY DEALING WITH 2311 01:55:54,362 --> 01:55:58,299 ANY OF THESE OR MAYBE IT'S A 2312 01:55:58,299 --> 01:55:59,734 GENERAL CONSIDERATION OF 2313 01:55:59,734 --> 01:56:02,036 EPIDEMIOLOGY ITSELF. 2314 01:56:02,036 --> 01:56:02,670 DO YOU WANT TO INFORM US ABOUT 2315 01:56:02,670 --> 01:56:05,373 THAT? 2316 01:56:05,373 --> 01:56:07,842 >> I WOULD SAY THAT I MEANT BY 2317 01:56:07,842 --> 01:56:16,017 THAT THAT NONE OF THEM ARE FULLY 2318 01:56:16,017 --> 01:56:21,489 CONSISTENT WITH THE INCIDENCE 2319 01:56:21,489 --> 01:56:25,259 PATTERNS SO SURVEILLANCE OFFERS 2320 01:56:25,259 --> 01:56:26,894 CLUES AND WE LOOK AT DIFFERENCES 2321 01:56:26,894 --> 01:56:30,998 BY RACE AND ETHNICITY AND ATOMIC 2322 01:56:30,998 --> 01:56:34,035 SUBSITE AND BIOLOGICAL CHARA 2323 01:56:34,035 --> 01:56:36,570 CHARACTERISTICS AND ALL THESE 2324 01:56:36,570 --> 01:56:36,804 THINGS. 2325 01:56:36,804 --> 01:56:41,542 THERE HASN'T BEEN ANY STUDY THAT 2326 01:56:41,542 --> 01:56:51,085 I'VE SEEN WHERE YOU SAY AHA, 2327 01:56:51,085 --> 01:56:54,322 THIS MAKES SENSE AND MAY BE A 2328 01:56:54,322 --> 01:56:57,391 COMBINATION OF MANY CONTRIBUTING 2329 01:56:57,391 --> 01:56:57,758 FACTORS. 2330 01:56:57,758 --> 01:57:00,728 GENETIC SUSCEPTIBILITY IS ALWAYS 2331 01:57:00,728 --> 01:57:03,197 ASTOUNDING TO ME THAT ONLY 23% 2332 01:57:03,197 --> 01:57:05,933 OF HEAVY SMOKERS DEVELOP LUNG 2333 01:57:05,933 --> 01:57:08,569 CANCER DESPITE THE RISK BEING 25 2334 01:57:08,569 --> 01:57:11,539 TIMES THAT OF NON-SMOKERS. 2335 01:57:11,539 --> 01:57:12,106 IT'S HARD TO WRAP YOUR HEAD 2336 01:57:12,106 --> 01:57:22,249 AROUND. 2337 01:57:29,156 --> 01:57:30,491 IT'S COMPLICATED. 2338 01:57:30,491 --> 01:57:32,426 THAT'S ALL I MEANT FOR THAT IS 2339 01:57:32,426 --> 01:57:34,929 IT DOESN'T NECESSARILY FIT ABOUT 2340 01:57:34,929 --> 01:57:36,797 WHAT WE KNOW ABOUT THE PATTERNS 2341 01:57:36,797 --> 01:57:37,598 WE'RE SEEING. 2342 01:57:37,598 --> 01:57:40,301 >> WHY DO YOU THINK CANCERS OF 2343 01:57:40,301 --> 01:57:46,240 THE SMALL INTESTINE ARE RARE, 2344 01:57:46,240 --> 01:57:47,174 RARE, RARE? 2345 01:57:47,174 --> 01:57:52,313 WHEREAS CANCERS OF THE LARGE 2346 01:57:52,313 --> 01:57:57,184 INTESTINE AS YOU'VE DESCRIBED 2347 01:57:57,184 --> 01:57:59,387 ARE MAJOR HEALTH CHALLENGES. 2348 01:57:59,387 --> 01:58:00,855 >> A CLASSIC QUESTION TO WHICH 2349 01:58:00,855 --> 01:58:03,124 THERE IS NOT AN ANSWER. 2350 01:58:03,124 --> 01:58:06,193 THOUGH THE BACTERIA POPULATION 2351 01:58:06,193 --> 01:58:08,729 OF THE SMALL BOWEL IS MUCH 2352 01:58:08,729 --> 01:58:11,532 SCANTER THAN IN THE LARGE BOWEL. 2353 01:58:11,532 --> 01:58:13,467 WE USED TO THINK THE SMALL BOWEL 2354 01:58:13,467 --> 01:58:16,637 IS STERILE, THAT'S NOT THE CASE 2355 01:58:16,637 --> 01:58:20,908 BUT HAS A MUCH LOWER MICROBIOME 2356 01:58:20,908 --> 01:58:24,645 BOTH NUMERICALLY IN TERMS OF 2357 01:58:24,645 --> 01:58:25,246 SPECIES. 2358 01:58:25,246 --> 01:58:27,715 IF THERE IS A MICROBIOME 2359 01:58:27,715 --> 01:58:28,783 CO-FACTOR IT'S LIKELY MISSING IN 2360 01:58:28,783 --> 01:58:37,291 THE SMALL BOWEL. 2361 01:58:37,291 --> 01:58:38,826 I DON'T THINK WE UNDERSTAND WHY 2362 01:58:38,826 --> 01:58:42,463 ONE ORGAN IS PROTECTED AND THE 2363 01:58:42,463 --> 01:58:43,731 OTHER IS NOT. 2364 01:58:43,731 --> 01:58:46,600 >> COULD IT BE RELATED TO 2365 01:58:46,600 --> 01:58:47,701 CELLULAR TURNOVER RATES? 2366 01:58:47,701 --> 01:58:58,112 >> NO, THEY'RE SIMILAR. 2367 01:59:06,387 --> 01:59:09,523 >> THERE'S CELLS IN THE LARGE 2368 01:59:09,523 --> 01:59:12,660 INTESTINE AND NOT IN THE COLON. 2369 01:59:12,660 --> 01:59:15,529 >> REBECCA HOW EFFECTIVE ARE 2370 01:59:15,529 --> 01:59:18,899 TESTING THE STOOL FOR BLOOD? 2371 01:59:18,899 --> 01:59:21,936 HOW EFFECTIVE IS THAT AS A 2372 01:59:21,936 --> 01:59:25,206 SIMPLER PROCEDURE THAN 2373 01:59:25,206 --> 01:59:26,540 COLONOSCOPY IN EARLY DETECTION 2374 01:59:26,540 --> 01:59:29,543 OF COLON CANCER? 2375 01:59:29,543 --> 01:59:33,147 >> IT'S A GREAT QUESTION BECAUSE 2376 01:59:33,147 --> 01:59:36,283 THE ABSOLUTE RISK OF DISEASE IN 2377 01:59:36,283 --> 01:59:41,922 PEOPLE UNDER 50 IS STILL VERY 2378 01:59:41,922 --> 01:59:45,392 LOW. 2379 01:59:45,392 --> 01:59:47,995 AND THERE'S AN IMPORTANT OPTION 2380 01:59:47,995 --> 01:59:48,996 AND BECAUSE IT'S MORE 2381 01:59:48,996 --> 01:59:52,066 CONVENIENCE AND YOU CAN DO IT IN 2382 01:59:52,066 --> 01:59:52,299 PRIVATE. 2383 01:59:52,299 --> 01:59:54,201 THESE PEOPLE ARE BUSY. 2384 01:59:54,201 --> 01:59:57,938 80% OF PEOPLE DIAGNOSED WITH 2385 01:59:57,938 --> 01:59:59,907 EARLY ONSET COLORECTAL CANCER 2386 01:59:59,907 --> 02:00:02,443 HAVE SMALL CHILDREN SO IT'S A 2387 02:00:02,443 --> 02:00:03,043 DIFFERENT POPULATION THAN IT 2388 02:00:03,043 --> 02:00:08,082 USED TO BE. 2389 02:00:08,082 --> 02:00:12,853 AND IN TERMS OF AND IN TEMS OF 2390 02:00:12,853 --> 02:00:14,188 REDUCES DEATHS COMPARABLY IT 2391 02:00:14,188 --> 02:00:16,223 DOESN'T REDUCE INCIDENTS IN THE 2392 02:00:16,223 --> 02:00:22,196 SAME WAY AS COLONOSCOPY. 2393 02:00:22,196 --> 02:00:27,568 ALTHOUGH IT SHOWS A REDUCTION IN 2394 02:00:27,568 --> 02:00:30,037 INCIDENTS UP TO 20% FOR STOOL 2395 02:00:30,037 --> 02:00:30,471 TESTING. 2396 02:00:30,471 --> 02:00:31,639 THE PROBLEM WITH STOOL TESTING 2397 02:00:31,639 --> 02:00:34,208 IS IT HAS TO BE DONE ON A 2398 02:00:34,208 --> 02:00:42,182 REGULAR BASIS SO IF IT'S A FECAL 2399 02:00:42,182 --> 02:00:43,651 BLOOD TEST IT HAS TO BE DONE 2400 02:00:43,651 --> 02:00:43,918 ANNUALLY. 2401 02:00:43,918 --> 02:00:45,686 IT'S DIFFICULT TO ENSURE PEOPLE 2402 02:00:45,686 --> 02:00:46,820 ARE DOING THAT AND THEN IF 2403 02:00:46,820 --> 02:00:48,556 THERE'S A POSITIVE TEST IT HAS 2404 02:00:48,556 --> 02:00:53,794 TO BE FOLLOWED UP WITH A 2405 02:00:53,794 --> 02:00:54,995 COLONOSCOPY. 2406 02:00:54,995 --> 02:00:57,698 THERE ARE CHALLENGES BUT THIS IS 2407 02:00:57,698 --> 02:01:01,035 HOW THEY SCREEN IN MOST OTHER 2408 02:01:01,035 --> 02:01:01,302 COUNTRIES. 2409 02:01:01,302 --> 02:01:04,171 THEY USE STOOL TESTING. 2410 02:01:04,171 --> 02:01:08,409 SO IT'S EFFECTIVE AND I THINK IT 2411 02:01:08,409 --> 02:01:11,779 SHOULD BE GIVEN AS AN OPTION TO 2412 02:01:11,779 --> 02:01:14,615 THESE YOUNGER ADULTS ESPECIALLY 2413 02:01:14,615 --> 02:01:15,182 WHO DON'T HAVE OTHER RISK 2414 02:01:15,182 --> 02:01:19,153 FACTORS. 2415 02:01:19,153 --> 02:01:21,188 >> WE HAVE ANOTHER HERE. 2416 02:01:21,188 --> 02:01:23,591 DOES YOUR DATA SUGGEST WHAT IS 2417 02:01:23,591 --> 02:01:26,193 YOUR DATA SUGGEST AS TO WHETHER 2418 02:01:26,193 --> 02:01:29,597 SCREENING COLONOSCOPY IS A GOOD 2419 02:01:29,597 --> 02:01:32,232 THING FOR PEOPLE SAY OVER THE 2420 02:01:32,232 --> 02:01:36,103 AGE OF I THINK IT WOULD BE 70 OR 2421 02:01:36,103 --> 02:01:37,805 75 IN YOUR DATA? 2422 02:01:37,805 --> 02:01:42,509 WHEN DO YOU STOP DOING ROUTINE 2423 02:01:42,509 --> 02:01:43,978 COLONOSCOPY BASED ON 2424 02:01:43,978 --> 02:01:44,411 EPIDEMIOLOGIC DATA? 2425 02:01:44,411 --> 02:01:48,582 >> THAT'S A GREAT QUESTION. 2426 02:01:48,582 --> 02:01:53,153 THE ACS GUIDELINES DIFFER FROM 2427 02:01:53,153 --> 02:01:57,791 THE U.S. GUIDELINE US BECAUSE WE 2428 02:01:57,791 --> 02:01:58,959 RECOMMEND PEOPLE SHOULD SCREEN 2429 02:01:58,959 --> 02:02:00,828 AS LONG AS THEY HAVE A 10-YEAR 2430 02:02:00,828 --> 02:02:03,197 LIFE EXPECTANCY, ARE IN GOOD 2431 02:02:03,197 --> 02:02:03,597 HEALTH. 2432 02:02:03,597 --> 02:02:05,666 PEOPLE ARE LIVING LONGER AND 2433 02:02:05,666 --> 02:02:10,204 IT'S REALLY HARD TO IDENTIFY 2434 02:02:10,204 --> 02:02:11,672 THAT CUT POINT. 2435 02:02:11,672 --> 02:02:13,240 WHEREAS THE TASK FORCE 2436 02:02:13,240 --> 02:02:14,808 RECOMMENDS PEOPLE STOP SCREENING 2437 02:02:14,808 --> 02:02:15,776 AT 75. 2438 02:02:15,776 --> 02:02:18,679 I THINK IT SHOULD BE AN 2439 02:02:18,679 --> 02:02:22,182 INDIVIDUAL CHOICE BETWEEN THE 2440 02:02:22,182 --> 02:02:29,723 PATIENT AND THEIR PHYSICIAN. 2441 02:02:29,723 --> 02:02:31,425 IT'S A LOT OF SCREENING. 2442 02:02:31,425 --> 02:02:34,028 WE HAD SCREENING OVER 75 IN THAT 2443 02:02:34,028 --> 02:02:37,131 PREVALENCE FIGURE AND PEOPLE DO 2444 02:02:37,131 --> 02:02:43,303 SCREEN AND SO I AM NOT A 2445 02:02:43,303 --> 02:02:46,206 SCREENING EFFORT WOULD SAY IT'S 2446 02:02:46,206 --> 02:02:47,808 AN INDIVIDUAL CHOICE OVER 75. 2447 02:02:47,808 --> 02:02:49,510 >> I CONCUR. 2448 02:02:49,510 --> 02:02:53,681 >> SANDY, AS YOU LOOK TO THE 2449 02:02:53,681 --> 02:02:58,185 FUTURE, DO YOU SEE PROJECTS LIKE 2450 02:02:58,185 --> 02:03:02,089 ALL OF US AND THESE MASSIVE 2451 02:03:02,089 --> 02:03:07,027 ACCUMULATION OF SEQUENCE DATA 2452 02:03:07,027 --> 02:03:07,561 AND LARGE NUMBERS OF THE 2453 02:03:07,561 --> 02:03:10,097 POPULATION? 2454 02:03:10,097 --> 02:03:13,300 DO YOU SEE THAT AS A POTENTIAL 2455 02:03:13,300 --> 02:03:16,737 WAY FOR IDENTIFYING RISK FACTORS 2456 02:03:16,737 --> 02:03:17,571 OVER THE LONG RUN FOR COLON 2457 02:03:17,571 --> 02:03:21,341 CANCER? 2458 02:03:21,341 --> 02:03:29,717 WHAT IS YOUR -- WHAT COMES NEXT? 2459 02:03:29,717 --> 02:03:33,754 >> THERE'S BEEN LARGE NUMBERS OF 2460 02:03:33,754 --> 02:03:35,756 GENOME WIDE ASSOCIATION STUDIES 2461 02:03:35,756 --> 02:03:40,661 FOR COLON CANCER. 2462 02:03:40,661 --> 02:03:43,697 THERE'S TENS OF THOUSANDS OF 2463 02:03:43,697 --> 02:03:49,803 INDIVIDUALS WITH RISK ALLELES. 2464 02:03:49,803 --> 02:03:52,372 I'M NOT SURE ANY OF IT HAS BEEN 2465 02:03:52,372 --> 02:03:53,240 CLINICALLY ACTIONABLE AND MY 2466 02:03:53,240 --> 02:03:55,609 GUESS WOULD BE THE POWER OF IT 2467 02:03:55,609 --> 02:03:59,747 HAS BEEN RESTRICTED BECAUSE IT 2468 02:03:59,747 --> 02:04:03,117 HASN'T BEEN WELL INTEGRATED WITH 2469 02:04:03,117 --> 02:04:04,918 THE TYPE OF EPIDEMIOLOGY THAT 2470 02:04:04,918 --> 02:04:08,956 REBECCA REPRESENTS. 2471 02:04:08,956 --> 02:04:14,194 AND IF YOU WANT TO FIND RISK 2472 02:04:14,194 --> 02:04:17,731 FACTORS FOR COLORECTAL CANCER 2473 02:04:17,731 --> 02:04:19,767 YOU'LL PROBABLY HAVE TO ANNOTATE 2474 02:04:19,767 --> 02:04:23,737 THE DATABASES NOT JUST WITH 2475 02:04:23,737 --> 02:04:27,241 GENETIC ALLELES BUT WITH MASSIVE 2476 02:04:27,241 --> 02:04:28,008 AMOUNTS OF DEMOGRAPHIC DATA AND 2477 02:04:28,008 --> 02:04:28,942 EXPOSURE DATA SO YOU CAN 2478 02:04:28,942 --> 02:04:29,443 RECOGNIZE THE PATTERNS. 2479 02:04:29,443 --> 02:04:29,510 2480 02:04:30,677 --> 02:04:35,616 >> OKAY. 2481 02:04:35,616 --> 02:04:36,850 WE'RE ALMOST OUT OF TIME. 2482 02:04:36,850 --> 02:04:38,719 >> I THINK WE ARE. 2483 02:04:38,719 --> 02:04:40,020 >> WOULD YOU PLEASE HAVE THE 2484 02:04:40,020 --> 02:04:48,729 LAST WORD AS TO WHAT YOU SEE ARE 2485 02:04:48,729 --> 02:04:51,698 THE CHALLENGES AND WHAT DOES THE 2486 02:04:51,698 --> 02:04:53,300 FUTURE HOLD WITH RESPECT 2487 02:04:53,300 --> 02:04:54,234 PARTICULARLY WITH EPIDEMIOLOGY 2488 02:04:54,234 --> 02:04:57,538 IN THE STUDY OF THIS DISEASE? 2489 02:04:57,538 --> 02:05:01,375 >> I THINK THAT THERE SHOULD BE 2490 02:05:01,375 --> 02:05:03,110 A LITTLE BIT -- THERE'S A LOT 2491 02:05:03,110 --> 02:05:05,179 OF -- IT'S VERY IMPORTANT TO 2492 02:05:05,179 --> 02:05:07,614 FOCUS ON RESEARCH AND TRY TO 2493 02:05:07,614 --> 02:05:10,184 IDENTIFY THE CAUSE BUT GIVEN ALL 2494 02:05:10,184 --> 02:05:11,451 THE CHALLENGES THAT WE'VE 2495 02:05:11,451 --> 02:05:15,489 DISCUSSED HERE, I THINK THERE 2496 02:05:15,489 --> 02:05:17,090 SHOULD BE A LITTLE MORE EMPHASIS 2497 02:05:17,090 --> 02:05:20,961 ON WHAT WE CAN DO NOW. 2498 02:05:20,961 --> 02:05:23,096 WE HAVE THIS GROWING BURDEN. 2499 02:05:23,096 --> 02:05:23,664 IT'S A VERY UNIQUE PATIENT 2500 02:05:23,664 --> 02:05:29,903 POPULATION. 2501 02:05:29,903 --> 02:05:31,638 THE WAY THESE PEOPLE ARE BEING 2502 02:05:31,638 --> 02:05:36,743 TREATED IS NOT MEETING THEIR 2503 02:05:36,743 --> 02:05:36,944 NEEDS. 2504 02:05:36,944 --> 02:05:40,080 A LOT OF COLORECTAL PATIENTS 2505 02:05:40,080 --> 02:05:42,916 COME OUT OF TREATMENT BEING 2506 02:05:42,916 --> 02:05:44,585 INFERTILE AND THERE WAS NO 2507 02:05:44,585 --> 02:05:47,788 CONVERSATION ABOUT OPTIONS FOR 2508 02:05:47,788 --> 02:05:48,255 PRESERVING FERTILITY. 2509 02:05:48,255 --> 02:05:50,624 I THINK IT TYPICALLY IS THIS 2510 02:05:50,624 --> 02:05:53,160 WOULD NOT BE A DISEASE OF 2511 02:05:53,160 --> 02:05:55,229 SOMEONE CONCERNED ABOUT THEIR 2512 02:05:55,229 --> 02:05:55,495 FERTILITY. 2513 02:05:55,495 --> 02:05:59,466 I THINK THERE'S A LOT OF GAPS 2514 02:05:59,466 --> 02:06:01,068 THAT NEED TO BE CONSIDERED TO 2515 02:06:01,068 --> 02:06:04,204 HELP THESE PEOPLE WHO ARE 2516 02:06:04,204 --> 02:06:07,307 DEALING WITH THIS NOW. 2517 02:06:07,307 --> 02:06:11,245 WHENEVER WE LOOK FOR THE CAUSE 2518 02:06:11,245 --> 02:06:14,181 AND PERHAPS SCREENING MORE TOOL 2519 02:06:14,181 --> 02:06:17,484 TESTING AND ALSO I THINK STIGMA 2520 02:06:17,484 --> 02:06:23,857 IS A HUGE ISSUE. 2521 02:06:23,857 --> 02:06:26,293 THAT FAMOUS ACTOR THE BLACK 2522 02:06:26,293 --> 02:06:29,696 PANTHER ACTOR I'M FORGETTING HIS 2523 02:06:29,696 --> 02:06:32,833 NAME, NO ONE EVEN KNEW HE HAD 2524 02:06:32,833 --> 02:06:35,869 COLORECTAL CANCER UNTIL HE 2525 02:06:35,869 --> 02:06:36,103 PASSED. 2526 02:06:36,103 --> 02:06:37,938 I THINK IF WE COULD TALK ABOUT 2527 02:06:37,938 --> 02:06:40,507 THIS MORE LIKE WE'RE DOING TODAY 2528 02:06:40,507 --> 02:06:43,277 AND REDUCE THE STIGMA AND TALK 2529 02:06:43,277 --> 02:06:45,712 ABOUT SYMPTOMS, YOU KNOW, TALK 2530 02:06:45,712 --> 02:06:47,881 ABOUT RECTUM. 2531 02:06:47,881 --> 02:06:50,183 IT'S VERY INTERESTING. 2532 02:06:50,183 --> 02:06:52,619 WE CAN'T EVEN LOOK AT RECTAL 2533 02:06:52,619 --> 02:06:54,888 CANCER DEATHS SEPARATE FROM 2534 02:06:54,888 --> 02:06:56,290 COLON CANCER DEATHS BECAUSE 2535 02:06:56,290 --> 02:06:58,892 THERE'S SO MUCH 2536 02:06:58,892 --> 02:06:59,693 MISCLASSIFICATION BECAUSE FOR 2537 02:06:59,693 --> 02:07:01,261 YEARS PEOPLE REFERRED TO 2538 02:07:01,261 --> 02:07:04,865 COLORECTAL CANCER AS COLON 2539 02:07:04,865 --> 02:07:05,532 CANCER. 2540 02:07:05,532 --> 02:07:08,802 AND WE'D GET INQUIRIES FROM 2541 02:07:08,802 --> 02:07:10,037 CONSTITUENTS WELL, THE 2542 02:07:10,037 --> 02:07:13,073 INFORMATION SAYS COLON CANCER 2543 02:07:13,073 --> 02:07:14,541 AND THIS SAYS RECTAL CANCER AND 2544 02:07:14,541 --> 02:07:17,511 I DON'T KNOW IF THIS APPLIES TO 2545 02:07:17,511 --> 02:07:17,744 ME. 2546 02:07:17,744 --> 02:07:21,348 SO A LITTLE IN OUR MESSAGING 2547 02:07:21,348 --> 02:07:23,650 COULD GO A LONG WAY AND 2548 02:07:23,650 --> 02:07:24,751 CLARIFIES THE ETIOLOGY. 2549 02:07:24,751 --> 02:07:27,721 >> LISTEN, WE HAVE REACHED OUR 2550 02:07:27,721 --> 02:07:31,158 LIMIT BUT ON BEHALF OF ALL THE 2551 02:07:31,158 --> 02:07:33,827 PEOPLE LISTENING AND WE'LL SEND 2552 02:07:33,827 --> 02:07:36,530 YOU SOME INFORMATION AS TO HOW 2553 02:07:36,530 --> 02:07:37,798 MANY THERE WERE AND WHERE 2554 02:07:37,798 --> 02:07:40,734 THEY'RE DOING IT BUT WE WANT TO 2555 02:07:40,734 --> 02:07:43,937 REALLY THANK YOU VERY MUCH FOR 2556 02:07:43,937 --> 02:07:47,908 BRINGING TO LIGHT SOMETHING THAT 2557 02:07:47,908 --> 02:07:52,145 IS INCREASINGLY BECOMING A MORE 2558 02:07:52,145 --> 02:07:53,947 SERIOUS PROBLEM PARTICULARLY FOR 2559 02:07:53,947 --> 02:07:57,184 YOUNG PEOPLE AND PUTTING THIS IN 2560 02:07:57,184 --> 02:08:02,622 THE PERSPECTIVE OF BOTH THE 2561 02:08:02,622 --> 02:08:05,659 EPIDEMIOLOGY AND STUDIES OF 2562 02:08:05,659 --> 02:08:08,829 BASIC MECHANISMS DERIVED FROM 2563 02:08:08,829 --> 02:08:12,466 INHERITABLE DISORDERS PUTS US AT 2564 02:08:12,466 --> 02:08:15,435 THE FOREFRONT OF WHERE WE ARE 2565 02:08:15,435 --> 02:08:16,336 AND APPRECIATE YOU TAKING THE 2566 02:08:16,336 --> 02:08:18,572 TIME TO DO THIS. 2567 02:08:18,572 --> 02:08:20,273 THANK YOU AGAIN AND I THINK WE 2568 02:08:20,273 --> 02:08:22,242 HAVE TO DISCONNECT AT THIS POINT 2569 02:08:22,242 --> 02:08:32,652 AS OUR TIME HAS RUN OUT.