Vitamin D-associated genetic variation and risk of breast cancer in the breast and prostate cancer cohort consortium (BPC3).
Mondul AM., Shui IM., Yu K., Weinstein SJ., Tsilidis KK., Joshi AD., Agudo A., Berg CD., Black A., Buring JE., Chasman DI., Gaudet MM., Haiman C., Hankinson SE., Henderson BE., Hoover RN., Hunter DJ., Khaw K-T., Kühn T., Kvaskoff M., Le Marchand L., Lindström S., McCullough ML., Overvad K., Peeters PH., Riboli E., Ridker PM., Stram DO., Sund M., Trichopoulos D., Tumino R., Weiderpass E., Willett W., Kraft P., Ziegler RG., Albanes D.
BACKGROUND: Two recent genome-wide association studies (GWAS) identified SNPs in or near four genes related to circulating 25-hydroxyvitamin D [25(OH)D] concentration. To examine the hypothesized inverse relationship between vitamin D status and breast cancer, we studied the associations between SNPs in these genes and breast cancer risk in a large pooled study of 9,456 cases and 10,816 controls from six cohorts. METHODS: SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped and examined both individually and as a 4-SNP polygenic score. Logistic regression was used to estimate the associations between the genetic variants and risk of breast cancer. RESULTS: We found no association between any of the four SNPs or their polygenic score and breast cancer risk. CONCLUSIONS: Our findings do not support an association between vitamin D status, as reflected by 25(OH)D-related genotypes, and breast cancer risk. IMPACT: These findings may contribute to future meta-analyses and scientific review articles, and provide new data about the association between vitamin D-related genes and breast cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 627-30. ©2014 AACR.