By: Michelle Medina And Nanjika Small

1. Familial Risk And Pathological Outcomes Of Colorectal Cancer In An Asymptomatic General Population Cohort By: Michelle Medina And Nanjika Small

2. What is Colorectal Cancer? • Colorectal cancer, also known as colon cancer or bowel cancer, includes cancerous growths in the colon, rectum and appendix. • Most cases begin as small benign polyps. • It is the third most common form of cancer and the second leading cause of death in the Western World.

3. The colon

4. Colorectal Cancer

5. age polyp growth history of cancer heredity virus exposure diabetes Crohn’s disease sclerosing cholangitis diet physical inactivity alcohol consumption smoking Risk Factors of Colorectal Cancer

6. change in bowel habits blood in the stool rectal bleeding bowel obstruction fatigue jaundice narrow stool anemia unexplained weight loss hepatomegaly gas cramping abdominal pain feeling of partially full bowel Symptoms of Colorectal Cancer

7. Who gets colorectal cancer? • Everyone is affected by colorectal cancer. • People older than fifty are more susceptible to it. • Death rates for colorectal cancer among African Americans are about 30% higher than among Whites and more than two times higher than for Asian Americans, Pacific Islanders, American Indians, and Hispanics.

8. Screening Methods for Colorectal Cancer • FOBT – Fecal Occult Blood Testing • IFOBT – Immunochemical FOBT • Double-Contrast Barium Enema • Flexible Sigmoidoscopy • Colonoscopy • Virtual Colonoscopy

9. National Colonoscopy Study Design Annual FOBT Baseline and FHQ Annual Follow Up ENROLLMENT Asymptomatic Men and Women Age 40-69 RANDOM ASSIGNMENT Screening Colonoscopy Determination of Eligibility

10. National Colonoscopy Study Sites Group Health Cooperative Clinical Center University of Minnesota Clinical Center Mallory Institute Pathology Center MSKCC Coordinating Center Louisiana State University Clinical Center

11. Eligibility • Age 50-69 (40-69) • Men and women in ~ equal numbers • No prior colonoscopy or recent sigmoidoscopy • No IBD, FAP, colorectal cancer • No prior use of an implanted defibrillator • No serious comorbidity • Exclusions: MI (past year) and other heart problems, anticoagulants, cancer therapy

12. Purpose of Study • To establish a correlation between family history of colorectal cancer and present cases. • To determine if race is a major risk factor for colorectal cancer susceptibility.

13. Materials • FOBT Cards: The fecal occult blood test chemically checks your stool for hidden blood.

14. Materials Cont. • Flexible Sigmoidoscope: A short, flexible, lighted tube which transmits an image of the inside of the distal bowel about 60 cm into the colon.

15. Materials Cont. • Colonoscope: A thin, lighted tube used to look all around the inside of the colon.

16. Materials Cont. • Baseline Questionnaires: Collects participants’ information.

17. Materials Cont. • Family History Questionnaires: Collects patients’ family history of cancer.

18. Materials Cont. • Pathology Review Form: Used by our pathologist to review colonoscopy specimens.

19. Methods • Patients who have already been reviewed by the genetics review committee were analyzed. • Each participants’ colonoscopy results were queried. • Those with First Degree risk and those meeting the Amsterdam II criteria were sent high risk letters advising them to go see a genetics counselor. • Those who were at standard risk were sent standard risk letters advising them they had no outstanding risk for colorectal cancer.

20. Genetic Review Process FHQ Completed Pedigree Generated Genetic Review Meeting Higher Risk Reports Sent To Clinical Centers Clinical Centers Notify Higher Risk Participants 1 2 Standard Risk Higher Risk 3

21. Genetics Review Criteria • Amsterdam II • At least 3 relatives with HNPCC associated cancers (one a FDR of the other two) • CRC, Endometrial, Kidney, Ovarian, Stomach, Small Bowel, Renal Pelvis/Ureter • At least 2 successive generations affected • At least 1 diagnosed with cancer before the age of 50 • No FAP • First Degree • At least one immediate family member diagnosed with colorectal cancer prior to the age of 60. • Standard Risk • No outstanding family history of colorectal cancer

22. National Colonoscopy Study Sample Amsterdam II Pedigree Father's Mother [dx 30s] Father's Brother1 Father Mother [dx 50s] >= 70 [dx 50s] >= 70 PROBAND Brother1 Sister1 Sister2 50s 40s 50s 40s = Colorectal Cancer = Cancer Free

23. Pathology Review Process Polyps Diagnosed By Clinical Center’s Pathologist Reviewed By Unbiased Pathologist Colonoscopies Performed and Polyps Removed Colonoscopy Arm Sent for Colonoscopies Pathology Slides Are Requested By MSK Every 6 mo. FOBT(+)Results Sent for Colonoscopy

24. Familial Risk First Degree Amsterdam II Standard Risk Total Caucasian n(%) 13(52) 5(56) 169(42) 187(43) Minorities n(%) 4(16) 1(11) 50(12) 55(13) Unknown Race n(%) 8(32) 3(33) 182(45) 193(44) Total 25 9 401 435 Genetics Review Results

25. Genetics Review Results Percentage of Participants Familial Risk

26. Pathology Review Results Percentage of Participants Types of Polyps Found

27. Conclusion • More data is still needed for results to be conclusive. • The National Colonoscopy Study still has three more years before it ends therefore there is still more to be learned and much more data to be acquired.

28. Bibliography • Colon and Colorectal Cancer. 18 July 2006 <www.medicinenet.com>. • "Colon Cancer: Untangling Its Genetics." South African Medical Research Council. July 2005. 17 July 2006 <http://www.mrc.ac.za/mrcnews/july2005/colon/html>. • Colon Cancer. Mayo Clinic. 2005. 17 July 2006 <http://www.mayoclinic.com/health/colon-cancer/DS00035/DSECTION=7>. • Colorectal Cancer. Molecular Diagnostic Laboratory. The Colorectal Cancer Group at MDL. Molecular Diagnostic Laboratory. 18 July 2006 <www.mdl.dk/design/assets/images/CRC1_big.jpg>. • "Colorectal Cancer." Wikipedia. 28 July 2006. 17 July 2006 <http://en.wikipedia.org/wiki/Colorectal_cancer>. • Detailed Guide: Colon and Rectum Cancer. American Cancer Society. 2006. 1-5. 17 July 2006 <http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What_are_the_risk_factors_for_colon_and_rectum_cancer.asp>. • Fuchs, Charles S., Edward L. Giovannucci, Graham A. Colditz, David J. Hunter, Frank E. Speizer, and Walter C. Willett. "A Prospective Study of Family History and the Risk of Colorectal Cancer." New England Journal of Medicine 331 (1994): 1-13. 17 July 2006 <http://content.nejm.org/cgi/content/short/331/25/1669>. • Iammarino, Nicholas K. African Americans & Cancer. Intercultural Cancer Council. 2001. 17 July 2006 <http://iccnetwork.org/cancerfacts/cfs1.htm>. • Kelley, Robert B., Frank J. Domino, and Carolyn Lopez. "Colorectal Cancer Screening." Family Doctor. 2006. 17 July 2006 <http://familydoctor.org/556.xml>. • Minorities and Colorectal Cancer. Cancer Research and Prevention Foundation. Alexandria, VA, 2006. 17 July 2006 <http://www.preventcancer.org/colorectal/facts/minorities.cfm>. • Weaver, Charles H. Genetiv Testing for Colorectal Cancer. Ed. C. D. Buckner. Cancer Consultants. 2004. Sept. 2004 <http://patient.cancerconsultants.com/print_tnpv.aspx?id=739>.

29. Acknowledgments • Victoria Serrano (our mentor) • Epidemiology and Biostatistics Department • Dr. Sat Bhattacharya • Harlem Children Society • Memorial Sloan Kettering Cancer Center