COLON CANCER: Etiology, Detection, and Prevention. Angel A. Diaz, M.D. Board Certified Gastroenterologist

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1 COLON CANCER: Etiology, Detection, and Prevention Angel A. Diaz, M.D. Board Certified Gastroenterologist

2 Epidemiology Colorectal cancer is the 3rd most commonly diagnosed cancer and the 2nd leading cause of cancer death in the United States. 11% of all new cases of cancer are colorectal cancer. Approximately 148,000 new cases diagnosed each year. Approximately 58,000 Americans die annually of colon cancer. Male:female ratio 1:1 Despite the favorable natural history of colorectal cancer and the availability of a curative surgical procedure, the overall 5 year survival rate is 62%. This is mainly because only 35% of new colorectal cancers are diagnosed at a local stage (I or II).

3 Epidemiology continued 35% are diagnosed at a regionally advanced stage (IIor III) % are diagnosed at a metastatic stage. Only 10-15% of patients who have symptoms at initial diagnosis have early stage colorectal cancer. 5 year survival is 90% for localized colorectal cancer, 60% for regional spread, and 10% for distant metastases. The average person has a 6% overall lifetime risk of developing colorectal cancer. Incidence and mortality have declined over the past two decades.

4 Risk Factors Age: 80% of colorectal cancers occur in patients without risk factors other than age >50. The risk of having colon cancer under age 40 is 0.06% compared to 4.19% between ages Family history of colorectal cancer or adenomatous polyps. Certain hereditary conditions (FAP and HNPCC). IBD Diets high in saturated fat and/or low in fiber. Excess ETOH Sedentary lifestyle.

5 Risk Factors continued A history colonic adenomas increases one s risk of developing subsequent adenomas, especially if the adenoma was large >1cm with either tubulovillous or villous histology. Polyps are divided into 3 histologic types: tubular, tubulovillous, and villous. The risk that a polyp harbors invasive cancer is related to its size and histologic type. Polyps <1cm are associated with ~1% risk of harboring cancer; between 1-2cm the risk is ~10%; >2cm the risk is ~ 25%. In general, villous adenomas have 10x the risk of harboring cancer compared to tubular adenomas of the same size.

6 Environmental Factors Potentially Influencing Carcinogenesis in the Colon and Rectum Probably related high fat and low fiber consumption Possibly related environmental carcinogens and mutagens Fecapentaenes (from colonic bacteria) Heterocyclic amines (from charbroiled and fried meat and fish) Beer and ale consumption (especially rectal cancer) Low dietary selenium

7 Etiology Of Colon Cancer Familial and Environmental factors 92% HNPCC 5% - 6% Chronic Inflammatory Bowel Disease 1% FAP and Rare Syndromes 1%

8 Molecular Genesis of Sporadic and Familial Colorectal Cancer Sporadic cancers Multistep accumulation over many years of acquired somatic mutations and chromosomal deletions Oncogenes: when activated or mutated, give clone of epithelial cells a growth advantage Tumor suppressor genes: when inactivated or deleted, fail to regulate cell cycle, give clone of epithelial cells a growth advantage Familial cancers Inherited germ-line mutations affect every cell in the body, cause familial cancer predisposition

9 Recommendations for Prevention of Primary Colorectal Cancer Diet: low in fat, high in fruits, vegetables and fiber Supplements*: vitamins A, E, C; folate; calcium; selenium Life habits: activity, normal body weight, avoid smoking and excessive alcohol Medications*: Aspirin and other NSAIDs, postmenopausal hormonal replacement *pending positive chemoprevention trials

10 Recommendations for Prevention of Colorectal Cancer Secondary: resection of colorectal adenomas Cohort study: proctosigmoidoscopy screening reduced incidence of rectal cancer by 85% Case-control studies: endoscopy and polypectomy reduced mortality from distal cancer by 50% to 79% Prospective trial of colonoscopy, polypectomy, and surveillance: reduced incidence of colorectal cancer by 76% to 90% Gilbertsen 1978 Newcomb 1992, Selby 1992, Muller 1995 Winawer 1993

11 Screening Modalities FOBT Flexible sigmoidoscopy Barium enema Colonoscopy CT colonography

12 Distribution of Colorectal Cancers Within the Large Intestine. Only Half of Cancers Are Within Reach of the Flexible Sigmoidoscope.

13 Rate of Detection of Adenomatous Polyps and Cancers for Various Instruments Rigid sigmoidoscope 30% 35-cm flexible sigmoidoscope 40% 60-cm flexible sigmoidoscope 55% Colonoscope 95% Air-contrast barium enema 90% Single-column barium enema 85%

14 Screening and Surveillance of Relatives of Patients With Sporadic Colorectal Cancer or Adenomas Low familial risk: perform annual FOBT, colonoscopy every 5 years, beginning at age 40. If 1º relative with CRC or an adenoma after age 60 High familial risk: perform colonoscopy every 3-5 years after age 40 If 1º relative with CRC at a younger age, or multiple 1º, 2º, or 3º relatives with CRC Sibling with adenoma before age of 60 Sibling with an adenoma and a parent with CRC

15 Colorectal Cancer Screening Recommendations for Asymptomatic, Average-risk risk Population Begin screening both men and women at age 50 Annual FOBT, (colonoscopy for positive screen test) Colonoscopy every 10 years Individualize for age and comorbidity

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21 Signs and Symptoms of Colorectal Cancers Initial presentation: Most common with rightsided cases: Overt or occult rectal bleeding Iron deficiency anemia Most common with left sided cases: Change in bowel habits Abdominal discomfort Late cancers Abdominal pain Weight loss Abdominal mass