Abstract 2889: Folic acid for the prevention of colorectal adenomas: Combined analysis of randomized clinical trials
Authors: Jane C. Figueiredo, Leila A. Mott, Edward Giovannucci, Kana Wu, Matthew Grainge, Richard F. Logan, John A. Baron
Journal: Cancer Research (2010)

Abstract Studies have suggested that poor folate status is associated with a higher risk of colorectal adenomas and cancer. However, some epidemiological and animal studies have provided contradictory evidence. Data from a few randomized clinical trials of folic acid supplementation for the prevention of colorectal adenomas have been reported. Two small trials reported at least suggestions of benefit, but this was not observed in two much larger trials, the Aspirin/Folate Polyp Prevention Study (AFPPS) and the United Kingdom Colorectal Adenoma Prevention (ukCAP). Findings from Nurses’ Health Study/Health Professional Follow-Up Study (NHS/HPFS) showed no overall risk reduction, but some indications of decreased risks in selected subgroups of individuals. To obtain more precise clinical evidence on the effects of folic acid on incident adenoma occurrence, we conducted a collaborative pooled analysis of the largest trials: AFPPS, NHS/HPFS and the ukCAP trials, focusing on the treatment periods of the studies. To address the possibility that there may be subgroups of individuals who may be more susceptible to the effects of folic acid in the large bowel, we conducted a stratified analysis by selected patient characteristics and dietary exposures. Participants included 2,007 men and women with a recent history of adenomas randomized to 0.5 or 1.0 mg/day of folic acid (n=1,008) or placebo (n=999) who had a follow-up colonoscopy 6 to 42 months after randomization (mean=30.6 (SD=8.1) months). We used random-effects meta-analysis to estimate risk ratios (RR's) and 95% confidence intervals (CI). The RR comparing folic acid vs. placebo for the occurrence of at least one adenoma was 0.99 (95% CI=0.84−1.16). For advanced lesions, the RR was 1.05 (95% CI=0.80-1.39). There was a non-significant increased risk among individuals with two or more baseline adenomas (RR, 1.14; 95% CI=0.98 -1.33) and no association among those with only one adenoma at baseline (RR, 0.88; 95% CI=0.73-1.06, P-interaction=0.03). Folic acid supplementation was also associated with a non-significantly increased risk of adenomas for individuals in the highest tertile of baseline plasma folate (&amp;gt;25 nmol/L) (RR, 1.19; 95% CI=0.92-1.53), and a non-significantly lower risk in those in the lowest tertile (&amp;lt;13.5 nmol/L) (RR, 0.79; 95% CI=0.43-1.43, P-interaction=0.39). Among non-drinkers, there was a non-significant increase in risk of adenoma recurrence in the folic acid groups (RR=1.33, 95% CI=0.63-2.81), in contrast to a null effect among subjects who consumed one or more drinks per day (RR= 0.95, 95% CI=0.54-1.69, p-interaction=0.74). Similar results were observed for advanced lesions. Results from this pooled analysis suggest that during the first few years of folic acid use, there is no clear decrease or increase in the occurrence of new adenomas in patients with a recent adenoma history. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2889.