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 15 SNPs in eleven one-carbon metabolism-related genes (MTHFD1, MTRR, MAT1A, MAT2B, FOLR1, CBS, GLS, DNMT3B, UNG2, ADA, CDO1) were performed. Dietary 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. The associations between high adherence to the MDP and risk reduction of BC were 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, while for MTHFD1 (rs8003567) and CDO1 (rs34869) genotypes, women who take homozygous allele were less affected by adherence to the MDP than to women who take heterozygotes allele. Significant gene-diet interactions were observed between MTHFD1 (rs8003567) polymorphism and MDP on BC risk. 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.
Folate and other one-carbon metabolism–related nutrients and risk of postmenopausal breast cancer in the Cancer Prevention Study II Nutrition Cohort
