Submitted to: Gut
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/1/2010
Publication Date: 1/1/2011
Citation: Flood, A., Mason, J., Liu, Z., Cash, B., Schatzkin, A., Schoenfeld, P., Cross, A. 2011. Concentration of folate in colorectal tissue biopsies predicts prevalence of adenomatous polyps. Gut. 60(1):66-72. Interpretive Summary: Prior epidemiologic studies suggest that either dietary intake of folate, or blood levels, are predictors of the risk of developing pre-cancerous polyps of the colon and colon cancer itself. However, both of these measures of folate nutriture are merely proxy measures of folate in the tissue of interest, the colon. We therefore conducted a case-control study of folate levels in biopsies taken of normal colonic lining in approximately 800 women who had undergone routine screening colonoscopy. Low folate levels in the colon were found to be a predictor of the risk of having a pre-cancerous polyp. Moreover, there was an especially strong relationship between colonic folate levels and so-called ‘high-grade’ polyps, i.e.: those types of polyps that have a particularly high risk of evolving into cancers. These observations provide further confirmation that a low folate environment is one that predisposes to cancerous degeneration in the colon.
Technical Abstract: 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.