Vitamin D Receptor Gene Haplotypes and Polymorphisms and Risk of Breast Cancer: A Nested Case–Control Study
Cancer Epidemiol Biomarkers Prev; 21(10); 1856–67. ©2012 AACR.
Lawrence S. Engel 1, Irene Orlow 3, Camelia S. Sima 3, Jaya Satagopan 3, Urvi Mujumdar 3, Pampa Roy 3, Sarah Yoo 3, Dale P. Sandler 2, and Michael C. Alavanja 4
1 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill;
2 National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina;
3 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York; and
4 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
Corresponding Author: Lawrence S. Engel, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599. Phone: 919-962-2756; Fax: 919-966-2089; E-mail: Larry.Engel at unc.edu
Background: Observational and experimental studies suggest that vitamin D may influence breast cancer etiology. Most known effects of vitamin D are mediated via the vitamin D receptor (VDR). Few polymorphisms in the VDR gene have been well studied in relation to breast cancer risk and results have been inconsistent.
Methods: We investigated VDR polymorphisms and haplotypes in relation to breast cancer risk by genotyping 26 single nucleotide polymorphisms (SNP) that (i) had known/suspected impact on VDR function, (ii) were tagging SNPs for the three VDR haplotype blocks among whites, or (iii) were previously associated with breast cancer risk. We estimated odds ratios (OR) and 95% confidence intervals (CI) in relation to breast cancer risk among 270 incident cases and 554 matched controls within the Agricultural Health Study cohort.
Results: In individual SNP analyses, homozygous carriers of the minor allele for rs2544038 had significantly increased breast cancer risk (OR = 1.5; 95% CI: 1.0–2.5) and homozygous carriers of the minor allele for rs11168287 had significantly decreased risk (OR = 0.6; 95% CI: 0.4–1.0). Carriers of the minor allele for rs2239181 exhibited marginally significant association with risk (OR = 1.4; 95% CI: 0.9–2.0). Haplotype analyses revealed three haplotype groups (blocks “A,” “B,” and “C”). Haplotype GTCATTTCCTA in block B was significantly associated with reduced risk (OR = 0.5; 95% CI: 0.3–0.9).
Conclusions: These results suggest that variation in VDR may be associated with breast cancer risk.
Impact: Our findings may help guide future research needed to define the role of vitamin D in breast cancer prevention.
Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).
Received May 7, 2012, Revision received July 16, 2012, Accepted July 22, 2012.
©2012 American Association for Cancer Research.
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