Plasma folate and risk of colorectal cancer in a nested case-control study: the Japan Public Health Center-based prospective study

Objective There is some evidence that folate may prevent colorectal cancer by stabilizing DNA sufficiently and methylating DNA appropriately. Plasma folate is a good marker to assess folate status in the body, but it has not been adequately examined in prospective epidemiologic studies. We investigated the association between plasma folate and the risk of colorectal cancer in a nested case-control study. Methods During a 11.5-year follow-up, 375 newly diagnosed colorectal cancers were identified in a cohort of 38,373 adults who had returned their baseline questionnaires and provided blood samples. Two controls for each case were selected from the cohort. The odds ratios (OR) and 95% confidence intervals (CI) of colorectal cancer for plasma folate was estimated using the conditional logistic regression model adjusted for potential confounding factors. Results Plasma folate was not associated with the risk of colorectal cancer in either men or women, although a small reduction of OR in men was observed in the second (OR, 0.70; 95% CI, 0.37–1.3), the third (OR, 0.72; 95% CI, 0.38–1.3), and the highest quartiles (OR, 0.86; 95% CI, 0.45–1.6) without a dose–response relationship (P for trend 0.88). A similar association was observed in the risk of colon or rectal cancer. No statistical interaction with the risk of colorectal cancer was observed between plasma folate and alcohol consumption. Conclusion Our results did not support the hypothesis that a folate-rich status may prevent colorectal cancer, though that finding may be due to an insufficient number of folate-deficient subjects in our study population.