Folic acid supplementation and colorectal cancer risk: a meta-analysis

Aim: This meta-analysis aims to determine the effect of folic acid supplementation on colorectal cancer risk. Method: A structured search of the MEDLINE, EMBASE, Cochrane and CINAHL databases was undertaken in July 2008. All published full text English language articles were searched that included a randomized or pseudo-randomized comparison of subjects who received folate vs subjects who did not in relation to their risk of adenoma or advanced adenomatous lesions, including colorectal cancer. A weighted treatment effect (using fixed effects) was calculated across trials. Results: Overall, the risk of an adenomatous lesion was not increased (odds ratio 1.09, 95% confidence interval 0.93-1.28) among patients who received folate supplementation for up to 3 years; however, for those who received folate for over 3 years, the risk of an adenomatous lesion was increased (odds ratio 1.35, 95% confidence interval 1.06-1.70). The risk associated with treatment was the highest for the occurrence of an advanced lesion (odds ratio 1.50, 95% confidence interval 1.06-2.10). There was no significant statistical heterogeneity in the analyses. Conclusion: At the 3-year colonoscopic follow up, folate supplementation had no effect on adenoma recurrence overall. While colonic surveillance beyond 3 years revealed an increased risk of colorectal adenoma, especially advanced adenoma, among those participants randomized to the folate group. This meta-analysis challenges the results from epidemiological studies that folate status is inversely related to the risk of developing colorectal cancer.