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 3years; however, for those who received folate for over 3years, 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 3years 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.