Abstract
A diet rich in folate is associated with a reduced colorectal cancer risk, whereas the role of circulating levels is less clear. The aim of this study was to relate prediagnostic plasma folate, vitamin B12, and homocysteine concentrations to the risk of colorectal cancer. This was a prospective case-control study of 331 cases and 662 matched controls nested within the population-based Northern Sweden Health and Disease Study. Median follow-up time from recruitment to diagnosis was 10.8 years. Plasma folate concentrations were positively related to colorectal cancer risk; multivariate odds ratios were 1.62 [95% confidence intervals (CI), 1.08-2.42] and 1.42 (95% CI, 0.94-2.21) for the middle and highest versus lowest tertile, respectively. In subjects with follow-up <10.8 years, a statistically significant doubled risk was observed for the middle and highest versus lowest tertile, whereas findings for longer follow-up times were null. A positive risk relationship was also observed for tumor stage III-IV but not I-II. Plasma vitamin B12 concentrations were inversely associated with rectal cancer risk. Homocysteine was not significantly related to colorectal cancer risk. In this population-based, nested case-control study, low plasma folate concentrations were associated with a reduced colorectal cancer risk. This protective role was mainly observed in subjects with higher tumor stage or shorter follow-up time between recruitment and diagnosis. Low circulating folate status may protect against colorectal cancer or suppress progression of preneoplastic or neoplastic lesions. These findings may have relevance for the ongoing debate about mandatory folic acid fortification of flour.
Highlights
Dietary supplementation with 0.4 mg/d of folic acid, the synthetic form of the water-soluble vitamin folate, is recommended before and during early pregnancy to reduce the incidence of neural tube defects (NTD; ref. 1)
Plasma folate concentrations were positively related to colorectal cancer risk, with multivariate Odds ratios (OR) of 1.62 and 1.42 for the middle and highest versus lowest tertile, respectively
Plasma vitamin B12 concentrations were inversely associated with rectal cancer risk (P-trend 1⁄4 0.019); multivariate OR 0.46 for the middle versus lowest tertile and 0.46 for highest versus lowest tertile (Supplementary Table S2)
Summary
Dietary supplementation with 0.4 mg/d of folic acid, the synthetic form of the water-soluble vitamin folate (vitamin B9), is recommended before and during early pregnancy to reduce the incidence of neural tube defects (NTD; ref. 1). Have been obstructed by concerns of a possible role for folic acid in cancer development including, but not limited to, colorectal cancer development [2]. Results of prospective studies of circulating folate levels have been inconsistent, and have not confirmed a potential protective role of folate on colorectal cancer risk [7,8,9,10,11,12,13,14,15,16,17]. Many new colorectal cancer cases have been registered in the same northern Swedish cohort after the cutoff date for the previous study, and a new, larger, nonoverlapping study is, possible. A diet rich in folate is associated with a reduced colorectal cancer risk, whereas the role of circulating levels is less clear. The aim of this study was to relate prediagnostic plasma folate, vitamin B12, and homocysteine concentrations to the risk of colorectal cancer
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