MTHFR gene polymorphisms and circulating folate concentrations are associated with survival after breast cancer diagnosis

Abstract

We studied the influence of interactions between circulating serum folate concentrations and four polymorphic MTHFR loci [rs1476413, rs1801131 (A1298C), rs1801133 (C677T) and rs4846052] on overall survival after breast cancer diagnosis. Participants were post‐menopausal women diagnosed with breast cancer (n = 479). In the separate Cox proportional multivariate hazards models [controlled for disease stage, age at diagnosis, body mass index (BMI), parity, ER/PR status, alcohol use, vitamin use and energy intake], we found a significant inverse trend (p = 0.03; HR = 0.78, CI: 0.62 – 0.97) with increasing folate concentrations and reduced risk of dying. Also, only loci rs1801133 (C677T) was borderline significantly (p = 0.09; HR = 1.30, CI: 0.95 – 1.78) associated with survival, with the recessive allele increasing risk. The model with both circulating folate concentrations and the rs1801133 loci slightly modified the independent risk for circulating folate concentrations (p = 0.09; HR = 0.82, CI: 0.65 – 1.03) and for the rs1801133 loci (p = 0.14; HR = 1.26, CI: 0.94 – 1.73). These results suggest that serum folate concentrations at and/or after diagnosis are positively associated with survival after breast cancer diagnosis, and that the MTHFR rs1801133 loci may modify risk of dying, however larger studies are needed to more definitively assess these interactions. Supported by NCI grant K07 CA101964