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Colorectal adenomas are relatively prevalent in the general population and are considered the precursor lesions of most colorectal carcinomas. Inactivating mutations in the adenomatous polyposis coli (APC) gene are thought to be early, initiating events in colorectal carcinogenesis and seem to highly increase cells’ chances of tumor formation. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors previously reported to be associated with colorectal cancer risk and the occurrence of truncating (i.e., frameshift and nonsense) APC mutations in a Dutch case-control study of sporadic adenomatous polyps. The study population consisted of 278 cases and 414 polyp-free controls. Formalin-fixed, paraffin-embedded polyp tissue was available for all cases. Direct sequencing was used to screen the mutation cluster region of APC for truncating mutations. Usual dietary intake was assessed with a self-administered food frequency questionnaire. Case-control and case-case comparisons were conducted. Odds ratios (OR) and the corresponding 95% confidence intervals (95% CI) were calculated using multiple logistic regression models. All analyses were adjusted for age, sex, and total energy. Truncating APC mutations were detected in 161 (58%) of the 278 adenomas; frameshift mutations were observed most often (67% of all truncating APC mutations). Red meat consumption was significantly differently related to polyps with truncating APC mutation (APC+ polyps) compared with polyps without truncating APC mutation (APC- polyps) [OR (95% CI) for highest vs. lowest tertile, 0.5 (0.3-1.0)]. High intake of red meat and high fat intake seemed to increase the risk of APC- polyps in particular [APC+vs. controls: red meat, 1.0 (0.6-1.6); fat, 1.1 (0.6-1.9). APC-vs. controls: red meat, 1.8 (1.0-3.1); fat, 1.9 (1.0-3.7)]. Intake of carbohydrates was inversely associated with both polyp groups, most noticeably with APC- polyps. Consumption of dairy products decreased the risk of APC+ polyps as well as APC- polyps, while alcohol intake seemed to increase the risk of both polyp groups. However, like most other evaluated dietary factors, dairy products and alcohol were not distinctively associated with a specific APC status. In addition, none of the dietary factors was specifically associated with a particular type of truncating APC mutation. To conclude, our data suggest that red meat and fat may increase the risk of APC- polyps in particular, whereas carbohydrates may especially decrease the risk of APC- polyps. However, most evaluated dietary factors do not appear to be distinctively associated with APC+ polyps or APC- polyps but seem to affect the development of these two different, early stages in colorectal carcinogenesis equally.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]