Serial Fecal DNA testing vs FOBT for Colorectal Cancer Screening in an Average Risk Population: a blinded prospective cross-sectional study

Colorectal cancer (CRC) is the second leading cause of death in the United States, claiming 56,730 lives in 2004. 146,940 new cases are diagnosed each year, (age standardized incidence 53/100,000) making it 3rd in American cancer incidence, with a lifetime risk estimate of -61/6. Risk factors for CRC include but are not limited to inherited CRC syndromes, inflammatory bowel disease, diabetes mellitus and insulin resistance, alcohol use, smoking, radiation exposure, and red meat consumption. The mode of presentation of CRC follows one of three patterns. Sporadic disease (ie average risk) accounts for 70% of CRC cases. It occurs in individuals in whom there is no family history of CRC. Inherited syndromes account for <1 0% of CRC cases. These are divided as to whether colonic polyps are a major disease manifestation. Poyposis syndromes include Familial adenomatous polyposis. (FAP) and the hamartomatous polyposis syndromes (eg, Peutz-Jeghers, juvenile polyposis), while those without polyps include hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome 1), and the cancer family syndrome (Lynch syndrome 11). Familial CRC accounts for:5 25% of CRC. Affected patients have a family history of CRC, but the pattern is not consistent with one of the inherited syndromes. Regardless of their etiology, most CRC arises from adenomatous polyps (adenoma to carcinoma sequence (Figure 1)). Polyps are mucosal colonic protrusions that can be classified as hamartomatous (juvenile polyp), hyperplastic, or adenomatous. Only adenomas are premalignant, though <1% ever become malignant. Risk for malignant transformation are polyp anatomy (sessile), size (>2.5cm), and histology (villous). Polyps usually require at least 5 years of growth before becoming clinically significant. The progression from adenoma to carcinoma is driven by the accumulation of genetic mutations, as elucidated in 19W by Fearon and Vogelstein. Each mutation confers a selective growth advantage to the colonic epithelia[ cell. Important genetic events include: