Format

Send to

Choose Destination
Cancer Causes Control. 2015 Feb;26(2):187-203. doi: 10.1007/s10552-014-0497-9. Epub 2014 Nov 25.

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

Author information

1
Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, 7th Floor, New York, NY, 10032, USA. llr2124@columbia.edu.
2
Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, 7th Floor, New York, NY, 10032, USA.
3
Department of Medicine, Columbia University, New York, NY, USA.
4
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
5
Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
6
Department of Environmental Health, Columbia University, New York, NY, USA.
7
Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA.
8
Department of Preventive Medicine, Mt. Sinai School of Medicine, New York, NY, USA.
9
Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.

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.

PMID:
25421379
PMCID:
PMC4302042
DOI:
10.1007/s10552-014-0497-9
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center