Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk.
Cancer Causes Control. 2014 Nov 25. [Epub ahead of print]
Reimers LL1, Crew KD, Bradshaw PT, Santella RM, Steck SE, Sirosh I, Terry MB, Hershman DL, Shane E, Cremers S, Dworakowski E, Teitelbaum SL, Neugut AI, Gammon MD.
Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, 7th Floor, New York, NY, 10032, USA, llr2124 at columbia.edu.
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.
PMID: 25421379
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