Interactions between XRCC3 polymorphisms and circulating folate concentrations on survival after breast cancer diagnosis

Abstract

Inadequate folate has been associated with increased DNA damage and cancer outcomes. We studied the influence of interactions between circulating serum folate levels and five tagging SNPs in the XRCC3 DNA repair gene, on overall survival after breast cancer diagnosis. Participants were post‐menopausal women diagnosed with breast cancer (n = 479) between 1994 – 1995. The Illumina BeadLab 1000 SNP genotyping system was used for genotyping. Serum folate was measured by isotope‐dilution LC/MS/MS. 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 that the rs861531 XRCC3 loci was significantly (p = 0.03; HR: 1.64, CI: 1.1 – 2.5) associated with a 65% increased risk of dying. Compared to the models with the dietary biomarker and the XRCC3 loci alone, the hazards ratio for the model with both the dietary biomarker (p = 0.09; HR: 0.53, CI: 0.25 – 1.1) and the rs861531 loci (p = 0.03; HR: 1.65, CI:1.1 – 2.6) were not substantially influenced. These data suggest that circulating folate levels and XRCC3 polymorphic variant rs861531 have independent effects on overall survival after breast cancer diagnosis, with increased folate concentrations improving overall survival, while the recessive allele for rs861531 reducing overall survival after breast cancer diagnosis. Supported by NCI grant K07 CA101964