There is a complex interaction between environmental/dietary factors and genetics underlying the pathogenesis of colon
carcinogenesis. Little data exist concerning the impact of diet on the phenotypic expression of genetically linked
colon cancer. As a result, it has been difficult to develop rationally designed dietary intervention studies in first-degree relatives of patients with established
familial adenomatous polyposis (FAP),
hereditary nonpolyposis colorectal cancer (HNPCC) and other familial
colon cancer syndromes. Only 2 double-blinded, placebo-controlled trials have been published concerning the use of preventive strategies in patients with genetically inherited
colorectal cancer syndromes, both in patients with FAP. One study evaluated the effects of
vitamin C plus
vitamin E with or without a high-dose
wheat bran fiber supplement on the recurrence of rectal
adenomas. Over a 48-month intervention period, only the
wheat bran fiber intervention significantly reduced
polyp growth. A second study reported that intervention with the
NSAID sulindac for 9 months in young patients with FAP resulted in a significant reduction in both
polyp number and size in the rectosigmoid colon. All of the large-scale (i.e., >500 randomized participants) phase III nutrient or chemopreventive agent intervention studies thus far have targeted participants with a history of non-familial, sporadic colorectal
adenomas. Current clinical
adenoma trials do not measure whether the regimen being tested can prevent genotoxic events occurring in early stages of abnormal cell development that contribute to the eventual formation of
adenomas nor whether the agent(s) can inhibit events occurring during the progression of
adenomas to
carcinomas. Therefore, future clinical trial designs may have to consider (i) lengthening the clinical trial period before
adenomas develop, (ii) testing at early patient ages and/or (iii) measuring the growth of
adenomas as they progress to
carcinomas.