Common Genetic Variants in the Vitamin D Pathway Including Genome-Wide Associated Variants Are Not Associated with Breast Cancer Risk among Chinese Women

Abstract

Previous studies evaluating the association of vitamin D-related genetic variants with breast cancer risk have produced inconsistent results. We evaluated the association between breast cancer risk and 559 single-nucleotide polymorphisms (SNP) in 12 vitamin D-related genes, including 6 genes associated with circulating 25-hydroxyvitamin D [25(OH)D] level identified by recent genome-wide association studies (GWAS), using directly observed and imputed GWAS genotyping data from 2,919 breast cancer cases and 2,323 controls recruited in the Shanghai Breast Cancer Study. Of the SNPs studied, only rs12570116 in the ACADSB gene, rs4760658 in the VDR gene and rs6091822, rs8124792, and rs6097809 in the CYP24A1 gene, and rs10902845 in C10orf88 had a nominal association with breast cancer risk (P < 0.05 for all). None of these associations persisted after adjustment for multiple comparisons. The most extensively studied SNPs including rs10735810, also known as rs2228570 (Fok1, VDR), rs1544410 (Bsm1, VDR), and rs2296241 (CYP24A1), were not associated with breast cancer risk. GWAS-identified genetic variants that were associated with 25(OH)D were also not related to breast cancer risk. Our data suggest that genetic polymorphisms in vitamin D-related genes do not play a major role in breast cancer risk in Chinese women. Although our study confirms previously documented breast cancer risk factor associations, our null results suggest that common genetic variants in vitamin D genes and loci associated with control of vitamin D levels are not risk factors for breast cancer in Chinese women. Our data contribute to filling the gap in this field of research.