Background and aims Folate has been implicated as a potential aetiological factor for colorectal cancer. Previous research has not adequately exploited concentrations of folate in normal colonic mucosal biopsies to examine the issue.

Methods Logistic regression models were used to estimate ORs and 95% CIs of adenoma according to the tissue concentration of folate using asymptomatic average-risk women (40–70 years) in a colorectal cancer screening study. Of the 1593 eligible women who were offered enrolment, 1483 (93%) participated. Colonoscopy was complete to the caecum in 98.7% (1463/1483) of the subjects, and normal colonic tissue biopsies were obtained from 813 (56%) of these, of whom 170 had at least one adenoma.

Results A marginal reduction in risk for proximal adenomas (OR 0.56, 95% CI 0.29 to 1.09) but not distal adenomas (OR 1.01, 95% CI 0.43 to 2.37) was observed among women in the highest quintile of tissue folate concentration. A significant reduction in risk for advanced adenoma was observed for women in the highest quintile of tissue folate concentration (OR 0.24, 95% CI 0.06 to 0.93). Defining the outcome as proximal adenomatous and/or hyperplastic polyps, statistically significant inverse associations with tissue concentrations of folate were also observed (OR 0.54, 95% CI 0.31 to 0.95 for quintile 5 vs quintile 1).

Conclusions These findings are consistent with the hypothesis that folate status of colonic mucosa is an exposure that is aetiologically important in determining the risk of particular molecular subtypes of colorectal cancer.