GENETIC SCREENING FOR COLORECTAL-CANCER AND INTERVENTION

There is a complex interaction between environmental/dietary factors a nd genetics underlying the pathogenesis of colon carcinogenesis. Littl e data exist concerning the impact of diet on the phenotypic expressio n of genetically linked colon cancer. As a result, it has been difficu lt to develop rationally designed dietary intervention studies in firs t-degree relatives of patients with established familial adenomatous p olyposis (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 s yndromes, both in patients with FAP. One study evaluated the effects o f vitamin C plus vitamin E with or without a high-dose wheat bran fibe r supplement on the recurrence of rectal adenomas. Over a 48-month int ervention 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 rectosig moid colon. All of the large-scale (i.e., >500 randomized participants ) phase III nutrient or chemopreventive agent intervention studies thu s far have targeted participants with a history of non-familial, spora dic colorectal adenomas. Current clinical adenoma trials do not measur e whether the regimen being tested can prevent genotoxic events occurr ing in early stages of abnormal cell development that contribute to th e eventual formation of adenomas nor whether the agent(s) can inhibit events occurring during the progression of adenomas to carcinomas. The refore, future clinical trial designs may have to consider (i) lengthe ning the clinical trial period before adenomas develop, (ii) testing a t early patient ages and/or (iii) measuring the growth of adenomas as they progress to carcinomas. (C) 1996 Wiley-Liss, Inc.