Environmental Factors and Colorectal Tumor Risk in Individuals With Hereditary Nonpolyposis Colorectal Cancer

Background & Aims: Individuals with hereditary nonpolyposis colorectal cancer (HNPCC) are at increased risk for colorectal cancer. Environmental factors might play a role in HNPCC-associated carcinogenesis. The aim of this study was to gain insight into the effects of environmental factors on colorectal tumor risk in individuals with HNPCC. Methods: We examined associations between dietary factors, cigarette smoking, and HNPCC-associated colorectal tumors in a Dutch case-control study (145 cases, 103 tumor-free controls; all study participants were known or suspected carriers of a germline mutation in one of the DNA mismatch repair genes). We also assessed associations between the various environmental factors and occurrence of adenomatous polyposis coli (APC) mutations in HNPCC-associated polyps in a subset of the study population. Results: Fruit consumption was inversely associated with ever developing HNPCC-associated colorectal tumors (odds ratio [95% confidence interval] for highest vs lowest tertile, 0.4 [0.2-0.9]; Ptrend = .03); a borderline significant inverse association was observed for dietary fiber intake (0.5 [0.2-1.0]; Ptrend = .06). Cigarette smoking seemed to increase the risk of HNPCC-associated colorectal tumors. Truncating APC mutations were detected in 30 (37.5%) of the 80 available HNPCC-associated polyps; frameshift mutations were most common (73.3%). None of the evaluated environmental factors was distinctively associated with a specific APC status of the polyps. Conclusions: Our data suggest that fruit consumption and dietary fiber intake might decrease the risk of colorectal tumors in individuals with HNPCC, whereas cigarette smoking might increase the risk of HNPCC-associated colorectal tumors. The observed associations support the hypothesis that HNPCC-associated outcomes might be modified by environmental factors.