BIOL 207 Biology of Cancer Spring 2004
Lecture 16: "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
--colonoscopy
--barium enema
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
· first FDA approved anti-angiogenesis drug for advanced (metastatic) colon cancer is Avastin, a monoclonal antibody against VEGF (vascular endothelial growth factor), developed by Genentech
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, monitoring and possibly treatment of both hereditary and non-hereditary forms of colorectal cancer.
Video clip on hereditary colon cancer
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