CALCIUM MODULATION OF COLON CANCER INTERMEDIATE MARKERS

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A high risk for colon cancer may correlate positively with the, proliferative activity or enzymatic activity in colon mucosa as measured by several assays: tritiated thymidine autoradiography, bromodeoxyuridine immunoperoiddase, and ornithine decarboxylue activity. The proliferative activity of colonic crypt cells has been reported to be suppressed by the administration of oral calcium. Many issues remain to be explored in determining the precise role of calcium in the modulation of colonic cell proliferation and the validity of intermediate markers of proliferation in monitoring this offect. This study proposes to evaluate four high-risk groups for colorectal cancer: a) patients with previous sporadic-type colon cancer, b) patients with a previous colon cancer who are members of a family with hereditary non-polyposis colon cancer (HNPCC); c) asymptomatic individuals at 50% risk of developing colon cancer because of a family history of HNPCC; d) patients with familial polyposis coli (FPC). Following stratification to one of the risk-groups, subjects are randomized to receive either oral calcium (2 g/day) or placebo for 12 weeks, followed by a cross over to the altenate regimen for 12 weeks. Proliferative activity (tritiated thymidine, bromodeoxyuridine labeuing and omithine decarboxylase activity) are measured on rectal biopsy at study entry, and after each of the two study periods (ie placebo or CaCO3). Proliferative and enzymatic activity profiles will be developed for each high risk group and the degree of modulation by oral calcium administration determined. It is anticipated that subject enrolled will be followed prospectively in order to evaluate long-term trends of labelling activity, calcium modulation, and clinical correlation. Issues related to long-term cancer control objectives will be considered. These will include evaluation of subject recruitment, study compliance and drop-out, as well as overall patient acceptance of study requirements.