Colon Cancer A preventable disease

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Slide 1 :

Colon Cancer: A preventable disease Klaus Gottlieb, MD, FACP, FACG Spokane, WA

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Colon Cancer in the US Estimated new cases in 2001: 135,400 Estimated cancer deaths in 2001: 56,700 Life time risk 6 % males = females 2nd leading cause of cancer mortality American Cancer Society Surveillance Data

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Colon Cancer: Bridging the Gap Primary Prevention Secondary Prevention What can we do now: For average risk individuals For high risk individuals What may be possible in the future

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The Adenoma-Carcinoma Sequence

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Molecular Genetic Events

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High Risk Individuals One first degree relative triples risk Members of HNPCC families have a tenfold increase in life time risk Familial Polyposis patients are almost certain to get colon cancer at a young age Ulcerative Colitis sufferers have an increased risk depending on the duration of the disease

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Hereditary Non Polyposis Colon Cancer (HNPCC) Amsterdam Criteria Three or more relativeswith CRC (one must be first-degree relative of other two) Involves at least two generations One or more relatives with CRC before age 50 Endometrial cancer?

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HNPCC Clinical Characteristics Cancers are early onset cancer, usually under age 50Colorectal cancers usually demonstrate tumor microsatellite instability (MSI)Individuals with HNPCC develop polyps, but not in large numbers2/3 of colorectal cancers occur proximal to the splenic flexure of the colon (right sided)

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Genetic Testing for HNPCC Microsatellite Instability Testing in Identifying HNPCCMSI analysis identifies a genetic alteration in colorectal cancer that is characteristic (although not diagnostic) of HNPCC. In families with a moderate history of cancer, the presence of MSI indicates the likelihood of HNPCC. Genetic testing is warranted because MSI is present in 15% of sporadic cancer. Full sequencing for mutation analysis A commercially available test determines whether or not a person has a mutation in the MLH1 or MSH2 gene.

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Colon Cancer Prevention for Average Risk Individuals

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FOBT: A personal view Somewhat effective because it randomizes people between colonoscopy and doing nothing The random event is the presence or absence of irritated hemorrhoids

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In the Minnesota Colon Cancer Control Study, annual fecal occult blood testing reduced mortality from colorectal cancer by at least 33.4% The high positivity rate of FOBT (about 10%) may have occured for reasons other than a bleeding cancer or polyp Some of the benefit of FOBT screening may come from "chance" selection of persons for colonoscopic examination Authors used a simple mathematical model to simulate the course of a cohort of screened persons, incorporating published data including those from the Minnesota study Results suggest that one third to one half of the mortality reduction observed from FOBT screening in the Minnesota study may be attributable to chance selection for colonoscopy

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Molecular Stool TestsDetecting colorectal cancer in stool with the use of multiple genetic targets J Natl Cancer Inst 2001 Jun 6;93(11):858-65 Stool samples from 51 colorectal cancer patients were collected before they underwent colectomy Purified stool DNA samples were tested for three different genetic markers (TP53, BAT26 and K-RAS mutations). The three genetic markers together detected the majority — over 70 percent (36 of 51) — of the colorectal cancers.

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Colonoscopy: The Gold Standard

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New Medicare Guidelines Average risk individuals are entitled to a screening colonoscopy every 10 years If a Medicare beneficiary receives a screening sigmoidoscopy, the beneficiary must wait 48 months before becoming eligible for a screening colonoscopy Applicable since July 1, 2001

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Barium Enemas Medical records of 2193 consecutive colorectal cancer cases identified in 20 central Indiana hospitals were reviewed. The sensitivity of colonoscopy for colorectal cancer (95%) was greater than that for barium enema (82.9%), with an odds ratio of 3.93 for a missed cancer by barium enema compared with colonoscopy. Colonoscopy performed by gastroenterologists was more sensitive (97.3%) for cancer than colonoscopy by non-gastroenterologists (87%), with an odds ratio of 5.36 for a missed cancer by a non-gastroenterologist compared with a gastroenterologist. Rex DK Gastroenterology 1997 Jan;112(1):17-23

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Colorectal cancers usually demonstrate tumor microsatellite instability (MSI)2/3 of colorectal canc more Colorectal cancers usually demonstrate tumor microsatellite instability (MSI)2/3 of colorectal cancers occur proximal to the splenic flexure of the ... less
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