Single-Nucleotide Polymorphisms in Vitamin D-Related Genes May Modify Vitamin D-Breast Cancer Associations.

Abstract

Background: We previously observed that high serum 25-hydroxyvitamin D (25(OH)D; >38.0 ng/mL) was inversely associated with breast cancer. Here, we examined effect modification by SNPs in vitamin D-related genes.Methods: The Sister Study enrolled 50,884 U.S. women who had a sister with breast cancer, but who had never had breast cancer themselves. Using a case-cohort design, we compared 1,524 women who developed breast cancer within 5 years to 1,810 randomly selected participants. We estimated ratios of HRs (RHRs) for the 25(OH)D-breast cancer association per copy of the minor allele using Cox proportional hazards models. We considered 82 SNPs in 7 vitamin D-related genes (CYP24A1, CYP27B1, CYP2R1, GC, DHCR7/NADSYN1, RXRA, and VDR). We also tested gene-based interactions with 25(OH)D.Results: The SNP with the smallest interaction P value was rs4328262 in VDR (P = 0.0008); the 25(OH)D HR was 0.92 [95% confidence interval (CI), 0.68-1.24] among those homozygous for the common allele, and the minor allele was estimated to decrease the HR by 33% per copy (RHR = 0.67; 95% CI, 0.53-0.85). Five other VDR SNPs showed evidence of interaction at P < 0.05, as did one SNP in CYP2R1 and one in RXRA As a group, the 82 SNPs showed evidence of multiplicative interaction with 25(OH)D (P = 0.04). In gene-based tests, only VDR showed strong evidence of interaction (P = 0.04).Conclusions: SNPs in vitamin D-related genes may modify the association between serum 25(OH)D and breast cancer.Impact: This work strengthens the evidence for protective effects of vitamin D. Cancer Epidemiol Biomarkers Prev; 26(12); 1761-71. ©2017 AACR.

• Authors: Katie M O'Brien, Dale P Sandler, H Karimi Kinyamu, Jack A Taylor, Clarice R Weinberg
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 26 Issue 12 Pg. 1761-1771 (12 2017) ISSN: 1538-7755 [Electronic] United States
• PMID: 28830874 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Enzymes
• Receptors, Calcitriol
• Retinoid X Receptor alpha
• Vitamin D
• 25-hydroxyvitamin D

Topics

• Alleles
• Breast Neoplasms (blood, genetics, metabolism)
• Case-Control Studies
• Enzymes (genetics)
• Female
• Genotype
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prospective Studies
• Receptors, Calcitriol (genetics)
• Retinoid X Receptor alpha (genetics)
• Siblings
• Vitamin D (analogs & derivatives, blood, metabolism)