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BIOL 207 Biology of Cancer 3/18/02 Lecture 14: "Colon Cancer" Reading: Scientific American special issue pp. 92-93 Lecture: 1. Risk factors 2. Screening tests 3. Hereditary diseases associated with colon cancer Path of digestion (organ system handout--digestive system) mouth pharynx esophagus stomach small intestine large intestine (colon, rectum, anus) Colon cancer: Primary tumor colon or rectum, secondary tumor usually liver. Second leading cancer killer after lung cancer. Risk factors: heredity ~10% of cases presence of polyps= benign growths in intestinal lining smoking colitis or Crohn’s disease (diseases of GI tract) industrial or urban area? diet: high fiber, low fat? Screening: general population: early detection --digital rectal exam (age 40) --fecal “hemoccult” test detects blood in stool (age 50--> every 5 yrs.) hemoccult test --watch diet (no red meat or fish) 3 days prior; no vitamin C, fresh broccoli, cauliflower, aspirin --test done on sample of stool, blue color indicates trace of blood in stool --positive test must be rescreened for presence of cancer other confirming tests --sigmoidoscopy --colonscopy --barium enema 1 Only 38% of colon cancers detected in early stages Staging--Dukes classification TNM staging: Major stages I, II, III, IV Other markers of advanced cancer --CEA: carcinoembryonic antigen --DNA aneuploidy=missing or extra chromosomes Treatment surgical resection: remove tumor from section of colon and stitch back together; 75% cure rate chemotherapy or radiation therapy usually after surgery Hereditary colon cancer p53 tumor suppressor gene discovered by lab studying colon cancer (Dr. Bert Vogelstein) Other tumor suppressor genes specifically involved in hereditary colon cancers o APC gene: Responsible for hereditary FAP (famial adenomatous polyposis); located on chromosome 5. In FAP, patients have many polyps in colon and rectum. Mutations in APC initiate essentially all colorectal tumors. The protein encoded by APC is most likely involved in cell adhesion. Mutation of APC gene also leads to overexpression of the c-myc oncogene. o HNPCC gene: Gene responsible for hereditary nonpolyposis colorectal cancer. Patients with hereditary HNPCC get one or a few tumors of the colon. Due to defects in any of 6 genes; at least four genes encode subunits of DNA repair enzymes. Two of these genes are MSH2 and MLH1. Future: Use gene tests for APC, HNPCC genes, p53 and/or the oncogene ras for diagnosis, monitering and possibly treatment of both hereditary and nonhereditary forms of colorectal cancer. 2