Title: Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk.

Authors: Reimers, Laura L; Crew, Katherine D; Bradshaw, Patrick T; Santella, Regina M; Steck, Susan E; Sirosh, Iryna; Terry, Mary Beth; Hershman, Dawn L; Shane, Elizabeth; Cremers, Serge; Dworakowski, Elzbieta; Teitelbaum, Susan L; Neugut, Alfred I; Gammon, Marilie D

Published In Cancer Causes Control, (2015 Feb)

Abstract: 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.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).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).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.

PubMed ID: 25421379

MeSH Terms: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics*; Adult; Aged; Breast Neoplasms/blood; Breast Neoplasms/genetics*; Calcifediol/blood; Case-Control Studies; Female; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Middle Aged; Multivariate Analysis; Odds Ratio; Polymorphism, Single Nucleotide*; Receptors, Calcitriol/genetics*; Risk; Steroid Hydroxylases/genetics; Vitamin D-Binding Protein/genetics*; Vitamin D/analogs & derivatives*; Vitamin D/blood; Vitamin D/genetics; Vitamin D3 24-Hydroxylase/genetics*; Vitamins