Yao S et al. – The data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER–negative breast cancer in African ancestry (AA women.

• In a case (n=928)-control (n=843) study of breast cancer in AA and EA women, the authors measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status.

• More AAs had severe vitamin D deficiency (<10ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry.
• Associations for SNPs differed by race.
• Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR=0.53, 95% CI=0.31-0.79, p by permutation=0.03), but had no effect in EAs.
• The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction <0.10).
• SNP rs27622941 was associated with a >twofold increased risk of ER-negative breast cancer among AAs (OR=2.62, 95% CI=1.38-4.98), but had no effect in EAs.
• rs2209314 decreased risk among EAs (OR=0.38, 95% CI=0.20-0.73), with no associations in AAs.
• The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR=1.20, 95% CI=0.80-1.79) after adjusting for these two CYP24A1 SNPs.