Single-nucleotide polymorphisms in one-carbon metabolism genes, Mediterranean diet and the risk of pre- and postmenopausal breast cancer

Abstract

Background: One-carbon metabolism pathway could interfere with the carcinogenesis of breast cancer (BC). Dietary pattern plays an important role in one-carbon metabolism linking the combination of dietary micronutrients. Methods: We assessed associations between single-nucleotide polymorphisms (SNPs) of one-carbon metabolism, adherence to Mediterranean dietary pattern (MDP) and BC risk from a case-control study (818 cases, 935 controls) among Chinese female population. The genotyping of 10 SNPs in seven one-carbon metabolism-related genes (MTHFD1, MTRR, MAT2B, CDO1, FOLR1, UNG2, ADA) were performed. Dietary intake measurements were assessed by a validated food-frequency questionnaire. Gene-diet interactions were analyzed. Results: No evidence demonstrated SNPs of one-carbon metabolism or their haplotypes were associated with BC risk. High adherence to the Mediterranean dietary pattern decreased the risk of breast cancer among post- but not premenopausal women and the association was influenced by the SNPs genotype, with the increasing number of variant allele in MTHFD1 (rs11627387), MTHFD1 (rs2281603), MTRR (rs16879334), MTRR (rs2287780), MAT2B (rs4869087), FOLR1 (rs10501409), UNG2 (rs231622) and ADA (rs244072). The protective effect against BC risk from high adherence to the MDP was gradually weakened and disappeared. For MTHFD1 (rs8003567) and CDO1 (rs34869) genotypes, women with homozygous were less affected by adherence to the MDP than to women who with heterozygotes. No significant gene-diet interactions were observed.Conclusions: SNPs of one-carbon metabolism genes modify the effect of high adherence to MDP against BC risk in Chinese women, as potential effect modifiers. Genetic variants may influence the association between diet and BC risk.