) Adenocarcinoma of the large bowel continues to be a significant public health problem, ranking second as a cause of death due to cancer and representing 10 percent of all cancers. Early detection is now recognized as one of the most important factors in colorectal cancer prognosis. Currently available screening modalities that facilitate early detection are either very costly for general population screening (colonoscopy) or have low sensitivity and specificity for disease detection (fecal occult blood testing). To significantly impact colorectal cancer mortality rates, tools are needed that improve the ability to know which members of the population merit aggressive screening, or alternatively, tools are needed that are cost effective yet highly sensitive, such as tests that detect precancerous genetic alterations in colonocytes shed in stool. A promising strategy to move toward these goals is that of studying families that have had increased rates of colorectal cancer. These families, along with carefully selected controls, will permit examination of the genetic and environmental factors predisposing to colorectal cancer. Although significant progress has been made in identifying the uncommon, high penetrance genes in hereditary colon cancers, the identification of low penetrance genes or environmental factors that may account for the majority of familial colorectal cancer will require studies of large numbers of carefully ascertained families. In response to the National Cancer Institute's call for a Cooperative Family Registry for Epidemiologic Studies of Colon Cancer, the applicant proposes a process whereby 5,000 colorectal cancer probands will be surveyed for family history, and from this group 500 high risk families will be selected for further recruitment. Family recruitment for the registry will involve collection of clinical and epidemiologic data, plus collection of biologic specimens including blood and tumor. Similar ascertainment will be undertaken for both case- matched controls and colorectal cancer population controls. Tumor specimens from both cases and controls will be characterized with respect to expression of mismatch repair proteins as determined by immunohistochemistry. This application is for collaborative development of a durable resource that will provide high quality data and biologic materials to the most promising research efforts directed toward decreasing colorectal cancer mortality.
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