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Genetic polymorphisms in the one‐carbon metabolism pathway and breast cancer risk: A population‐based case–control study and meta‐analyses

Epidemiological evidence suggests that intake of folate and other B‐vitamins and genetic variants in the one‐carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. In a large population‐based case–control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 one‐carbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) = 0.84 (0.73–0.96) and 0.85 (0.62–1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p‐trend = 0.01, false discovery rate = 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Meta‐analyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one‐carbon metabolism pathway and breast cancer risk. © 2007 Wiley‐Liss, Inc.