Objective: The aim of this study is to assess the relationship between the single-nucleotide polymorphism (SNP) in the one-carbon metabolism pathway (MTR  rs1805087; MTHFR  rs1801133; ALDH1L1  rs2002287, rs2276731; DNMT1  rs16999593, rs2228611; DNMT3B  rs2424908) and the risk of female breast cancer (BC) in a Chinese population.
Methods: A population-based case–control study was conducted, involving a total of 439 BC patients and 439 age-matched healthy controls. We adopted Sequence MASSarray to identify genotyping, and used immunohistochemistry (IHC) to test the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissue.
Results: We found that rs16999593 (TC/CC vs TT: adjusted OR=1.38, 95% CI: 1.03– 1.84, p =0.030) was associated with an increased risk of BC, while rs2228611 was related to a decreased BC risk (GA/AA vs GG: adjusted OR=0.74, 95% CI: 0.56– 0.97, p =0.030). In addition, stratified analysis revealed that DNMT1  rs16999593, rs2228611 and ALDH1L1  rs2002287 contributed to the risk of BC, with associations with ER, PR and HER-2 expression.
Conclusion: In summary, this study revealed that DNMT1  rs16999593 and rs2228611 were associated with BC risk.
Keywords: one-carbon metabolism, DNA methylation, DNMT1 , SNP, breast cancer