Vitamin D, Vitamin D Receptor Polymorphisms and Breast Cancer Aggressiveness in African American and European American Women

摘要

Vitamin D may be associated with breast cancer (BC) of poor prognosis, particularly the triple-negative (TN) subtype, which may explain the strikingly high incidence of (TNBC) among African American (AA) women, because AAs have significantly lower vitamin D levels than European Americans (EAs). Pre-treatment 25OHD levels were available from 579 EA BC cases and 574 EA controls, and compared by tumor characteristics with control for covariates. In 547 AA and 381 EA BC patients and 461 AA and 382 EA controls, tagSNPs in VDR, CYP27B1 and CYP24A1 genes were typed. BC cases had lower 25OHD than controls. Among premenopausal women, serum 25OHD was lowest among TNBC cases. Every 10 ng/mL increase in 25OHD was associated with a 64% lower odds of having TNBC (OR=0.36, 95% CI=0.22-0.56). In AAs 4 VDR SNPs were associated with BC risk, including rs2239186 (p by permutation =0.03). Women with GG/GA had increased level of serum vitamin D, as well as lower risk of BC than those with AA genotype (OR=0.53, 95% CI=0.35-0.79). Two SNPs in CYP24A1 were associated with ER- cancer risk, and adding them into a base model including race, substantially reduced increased risk of ER- cancer with AA women. In conclusion, we found lower vitamin D levels in association with BC of poor prognosis, particularly TNBC among premenopausal women. The associations of SNPs in vitamin D-related genes differ by race, and may explain, in part, the higher risk of ER negative cancer in AA women.