Abstract
Purpose
Studies of vitamin D-pathway genetic variants in relation to cancer risk have been inconsistent. We examined the associations between vitamin D-related genetic polymorphisms, plasma 25-hydroxyvitamin D [25(OH)D], and breast cancer risk.
Methods
In a population-based case–control study of 967 incident breast cancer cases and 993 controls, we genotyped 25 polymorphisms encoding the vitamin D receptor (VDR) gene, 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D-binding protein (GC) and measured plasma 25(OH)D. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and 95 % confidence intervals (CIs).
Results
Among CYP24A1 polymorphisms, rs6068816 was associated with a 72 % reduction in breast cancer risk (TT vs. CC, OR 0.28, 95 % CI 0.10–0.76; p trend = 0.01), but for rs13038432, the 46 % decrease included the null value (GG vs. AA, OR 0.54, 95 % CI 0.17–1.67; p trend = 0.03). Increased risk that included the null value was noted for CYP24A1 rs3787557 (CC vs. TT, OR 1.34, 95 % CI 0.92–1.89). The VDR polymorphism, TaqI (rs731236), was associated with a 26 % risk reduction (TT vs. CC, OR 0.74, 95 % CI 0.56–0.98; p trend = 0.01). For other polymorphisms, ORs were weak and included the null value. The inverse association for plasma 25(OH)D with breast cancer was more pronounced (OR 0.43, 95 % CI 0.27–0.68) among women with the common allele for CYP24A1, rs927650 (p for interaction on a multiplicative scale = 0.01).
Conclusion
Breast cancer risk may be associated with specific vitamin D-related polymorphisms, particularly CYP24A1. Genetic variation in the vitamin D pathway should be considered when designing potential intervention strategies with vitamin D supplementation.
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Acknowledgments
This study is funded in part by Grants Nos. U01 CA/ES66572, P30ES009089, P30ES10126, from the National Cancer Institute and the National Institute of Environmental Health Sciences, an award from the Breast Cancer Research Foundation and the Jean Sindab Foundation. Laura Reimers was supported by a training grant from the National Cancer Institute (T32 CA009529). This manuscript was also made possible by Grant Number UL1 RR024156 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.
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Reimers, L.L., Crew, K.D., Bradshaw, P.T. et al. Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk. Cancer Causes Control 26, 187–203 (2015). https://doi.org/10.1007/s10552-014-0497-9
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DOI: https://doi.org/10.1007/s10552-014-0497-9