Plasma Vitamins B2, B6, and B12, and Related Genetic Variants as Predictors of Colorectal Cancer Risk

Abstract

Background: B-vitamins are essential for one-carbon metabolism and have been linked to colorectal cancer. Although associations with folate have frequently been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal cancer are scarce or inconclusive.Methods: We carried out a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, including 1,365 incident colorectal cancer cases and 2,319 controls matched for study center, age, and sex. We measured the sum of B2 species riboflavin and flavin mononucleotide, and the sum of B6 species pyridoxal 5′-phosphate, pyridoxal, and 4-pyridoxic acid as indicators for vitamin B2 and B6 status, as well as vitamin B12 in plasma samples collected at baseline. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for colorectal cancer were estimated using conditional logistic regression, adjusted for smoking, education, physical activity, body mass index, alcohol consumption, and intakes of fiber and red and processed meat.Results: The relative risks comparing highest to lowest quintile were 0.71 [95% confidence interval (95% CI), 0.56-0.91; P trend = 0.02] for vitamin B2, 0.68 (95% CI, 0.53-0.87; P trend <0.001) for vitamin B6, and 1.02 (95% CI, 0.80-1.29; P trend = 0.19) for vitamin B12. The associations for vitamin B6 were stronger in males who consumed ≥30 g alcohol/day. The polymorphisms were not associated with colorectal cancer.Conclusions: Higher plasma concentrations of vitamins B2 and B6 are associated with a lower colorectal cancer risk.Impact: This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(10); 2549-61. ©2010 AACR.

Low Folate Levels Are Associated with Reduced Risk of Colorectal Cancer in a Population with Low Folate Status

“…These results are similar to the findings of our previous report from the same population (9,31). Two prospective studies of circulating vitamin B12 have been published since, none of which found a statistically significant association between vitamin B12 and colorectal cancer risk (11,43).…”

Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas

“…Although reverse causality is a potential bias in a cross-sectional setting, colorectal adenoma is a preclinical disorder, which most likely has no systemic effects influencing one-carbon metabolism and related B-vitamins. Moreover, the inverse associations of vitamins B2 and B6 with colorectal adenoma are in line with observed inverse associations with colorectal cancer in prospective studies (25,27).…”

“…Vitamin B12 status was not associated with colorectal cancer in the majority of the studies (21,(24)(25)(26). In addition, plasma vitamin B2 has been reported to be not associated (24) or inversely associated (25) with colorectal cancer risk. On the other hand, vitamin B6 has consistently been associated with reduced colorectal cancer risk, as indicated by a recent meta-analysis on prospective studies (27).…”

Vitamins, minerals, essential fatty acids and colorectal cancer risk in the United Kingdom Dietary Cohort Consortium

“…[10][11][12] The other B vitamins have been little studied. 2,13 Calcium and vitamin D have been extensively studied in relation to the risk for colorectal cancer. 2 Several previous prospective studies have observed inverse associations of dietary calcium and of serum and dietary vitamin D with risk for colorectal cancer, 2,14 but the Women's Health Initiative randomized controlled trial did not find evidence of benefit with supplemental calcium and vitamin D, 15 and neither dietary calcium nor dietary vitamin D was associated with risk in our analysis.…”