Disturbances in DNA methylation have been hypothesized as being involved bt carcinogenesis. It has been proposed that dietary factors such as folate, alcohol, and methionine I?tay be associated with colon cancer because of their involvement in DNA methylation processes. Data from a targe retrospective population-based case-control study of incident colon cancer were used to evaluate whether intake of alcohol and other dietary factors involved in DNA methylation are associated with colon cancer. Dietary data were obtained using a detailed diet history questionnaire. We did not observe strong independent associations between folate, vitamin B-6, vitamin B-12, methionine, or alcohol and risk of colon cancer after adjusting far body size, physical activity, cigarette smoking patterns, energy intake, and dietary intake of fiber and calcium. However, it hen assessing the associations between colon cancer and a composite dietary profile based on alcohol intake, methionine, folate, vitamin B-12, and vitamin B-6, we observed a trend of increasing risk as one moved from a low- to a high-risk group. This trend was modest and most marked in those diagnosed at a younger age [odds ratio (OR) for men = 1.3, 95% confidence interval (CI) = 0.9-1.9; OR for women = 1.6, 95% CI = 1.0-2.6]. We observed that associations with this high-risk dietary profile were greater among those who took aspirin or nonsteroidal anti-inflammatory drugs on a regular basis and were younger at the time of diagnosis (men OR = 1.7, 35% CI = 1.0-3.2; women OR = 2.2, 95% CI = 1.0-4.8) and for distal tumors (men OR = 1.4 95% CI = 0.9-2.3; women OR = 2.0, 95% CI = 1.0-3.8). Findings from this study provide only limited support for previously reported associations between dietary factors involved in DNA methylation and risk of colon cancer.