Abstract A87: Folate and vitamin B6 intake and colorectal cancer risk in the CPS-II Nutrition Cohort

Background: High folate intake has been inversely associated with incident colorectal cancer risk. However, it is not clear whether folic acid, the synthetic folate added to foods and supplements, is as effective as natural folates. Vitamin B6, which is found in many of the same foods and participates in one-carbon metabolism with folate has also been inversely associated with colorectal cancer risk. Whether the associations between folate and vitamin B6 and risk of colorectal cancer are independent has not been investigated. Methods: The associations of folate and vitamin B6 intakes with colorectal cancer risk were investigated in the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort. Of the 43,512 men and 56,011 women who provided detailed dietary information in 1999, 526 men and 497 women were diagnosed with colorectal cancer between 1999 and 2007. Food frequency questionnaire (FFQ) responses, reported multivitamin and other supplement use, and composition values from the USDA were used to quantify intakes of natural folates (in food), dietary folate (natural food folates and folic acid from fortification), folic acid (in foods from fortification and from multivitamins and supplements), total folate (from all sources), dietary vitamin B6 (from food) and total vitamin B6 (from food, multivitamins and supplements). Cox proportional hazards modeling was used to calculate multivariate hazards ratios and 95% confidence intervals. Results: Higher intakes of natural folate (RRQ5vsQ1=0.82; 95% CI; 0.68, 1.01; p-trend=0.07), dietary folate (RRQ5vsQ1=0.83; 95% CI; 0.68, 1.02; p-trend=0.14), folic acid (RRQ5vsQ1=0.88; 95% CI; 0.72, 1.08; p-trend=0.09), and total folate (RRQ5vsQ1=0.79; 95% CI; 0.65, 0.97; p-trend=0.05) were associated with lower colorectal cancer risk, although not all results were statistically significant. Similarly, higher intakes of dietary B6 (RRQ5vsQ1=0.82; 95% CI; 0.67, 1.07; p-trend=0.07) and total vitamin B6 (RRQ5vsQ1=0.82; 95% CI; 0.67, 1.00; p-trend=0.12) also were associated with lower colorectal cancer risk. Exclusion of the first two years of follow-up strengthened the inverse associations with folate measures but attenuated associations with vitamin B6. Controlling for vitamin B6 intake did not substantively change risk estimates for measures of folate intake, although confidence intervals were widened. The associations of dietary and total vitamin B6 with colorectal cancer risk were somewhat attenuated but remained inverse when controlled for either dietary or total folate intake. Conclusions: Our findings add to the epidemiologic evidence which suggests that higher intakes of folate reduce colorectal cancer risk and indicate that synthetic folic acid is as effective as natural folates. The inverse association of vitamin B6 intake with colorectal cancer was somewhat weaker and may be due, at least in part, to the correlated intake of folate. While vitamin B6 intake did not appear to confound associations with folate, further studies with blood levels of these two nutrients might help to disentangle associations of folate and vitamin B6 with colorectal cancer risk. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A87.