Effective preventive measures against cancer of the large bowel have not been established, although diet offers promise for the development of successful interventions. In addition to changes in dietary fat and fiber, an increase in dietary calcium has been proposed to reduce the risk of large bowel cancer. In evaluating the effectiveness of these or other preventive efforts, reliance on the occurrence of large bowel cancer itself as an endpoint is impractical, because of the low probability of its occurrence among subjects under medical surveillance. In addition to adenoma formation, measurement of large bowel mucosa] proliferation has been proposed as a marker of cancer risk and as a possible endpoint for the study of preventive efforts. This proposal is for the measurement of rectal mucosal proliferation among participants in an on-going multicentered randomized trial of the effect of nutritional supplementation with calcium on the recurrence of adenomatous polyps of the large bowel. Subjects in the trial have had at least one documented adenomatous polyp immediately prior to entry, and have been judged free of remaining polyps in the large bowel by colonoscopy. They are randomized to receive either daily calcium carbonate supplementation (1200 mg calcium) or placebo, and undergo surveillance colonoscopy approximately one year and four years after the qualifying exam to detect incident polyps. 300 subjects will be recruited at the time of their one year colonoscopy for biopsy of the rectal mucosa, with subsequent assessment of labelling indices (and related measures) based on bromodeoxyuridine and proliferating cell nuclear antigen. The primary analysis will focus on (1) the difference in labelling indices at year 1 between subjects randomized to calcium, and those randomized to placebo; (2) the difference between the labelling indices in subjects who have a polyp recurrence in study years 2 through 4 and those who do not; and (3) the differences in labelling indices associated with age, gender, and dietary intake of fat, fiber, total calories, and various micronutrients. The study will have greater than 90% power to detect meaningful differences in all these analyses.
| Baron, J A; Wargovich, M J; Tosteson, T D et al. (1995) Epidemiological use of rectal proliferation measures. Cancer Epidemiol Biomarkers Prev 4:57-61 |
| Baron, J A; Tosteson, T D; Wargovich, M J et al. (1995) Calcium supplementation and rectal mucosal proliferation: a randomized controlled trial. J Natl Cancer Inst 87:1303-7 |
