Dietary Fiber or Piroxicam as Potential Cancer Prevention Agents: Effects on Rectal Epithelial Cell Proliferation in Humans at Increased Risk of Colon Cancer

Abstract

Over the past decade, there has been little improvement in outcome of treatment for advanced colon cancer. The best chance for cure remains early removal of a localized malignant tumor. Accordingly, much emphasis has been focused on screening, early detection and removal of recognized precursor lesions, namely adenomatous colon polyps. However, this approach is problematic in that current methods, such as testing of stool for occult blood and periodic examination of the rectum and colon by fiberoptic endoscopy, have either less than desired sensitivity or are expensive, entail some risk, detect only gross macroscopic lesions and do not address the persistence of abnormal colonic mucosal biology which imparts a continued cancer risk. However, the demonstration that colonic crypt epithelial cell proliferative activity (labeling index) which is increased in colon cancer was also abnormal in colon mucosa of patients with familial polyposis coli, who are known to be at high risk for developing cancer, provided a tool to assess for the presence of a subclinical or microscopic abnormality (Lipkin 1983, 1984). The subsequent reports that crypt cell proliferative activity was also increased in patients with sporadic colon adenomas, and that the labeling index in patients with familial polyposis could be changed toward normal by addition of calcium to the diet, provides evidence that this marker of crypt cell epithelial proliferative activity might be useful to evaluate cancer risk in certain patient groups and for assessing the effects of treatment interventions aimed at decreasing cancer risk (Lipkin 1985). We have used the tritiated thymidine labeling index to evaluate the effects of two proposed cancer prevention strategies, namely increased dietary fiber and treatment with the nonsteroidal anti-inflammatory drug (NSAID) piroxicam.