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Breast Cancer Research
Published in: Breast Cancer Research 2/2008

Open Access 01-04-2008 | Research article

Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk

Authors: Sascha Abbas, Alexandra Nieters, Jakob Linseisen, Tracy Slanger, Silke Kropp, Elke Jonny Mutschelknauss, Dieter Flesch-Janys, Jenny Chang-Claude

Published in: Breast Cancer Research | Issue 2/2008

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Abstract

Introduction

Vitamin D receptor (VDR) genotypes may influence breast cancer risk by altering potential anticarcinogenic effects of vitamin D, but epidemiological studies have been inconsistent. Effect modification by serum 25-hydroxyvitamin D (25 [OH]D), the biomarker for vitamin D status in humans, has rarely been examined.

Methods

We assessed the effects of two frequently analyzed polymorphisms (FokI and TaqI) and two potentially functional variants (VDR-5132 and Cdx2) in the VDR gene, which thus far have not been analyzed with respect to breast cancer risk, on postmenopausal breast cancer risk in a population-based, case-control study including 1,408 patients (cases) and 2,612 control individuals (controls) matched for year of birth. Odds ratios (ORs) for breast cancer adjusted for potential confounders were calculated for genotypes and estimated haplotypes.

Results

No differences in serum 25(OD)D concentrations by VDR genotype were observed. None of the analyzed polymorphisms was associated with overall risk for postmenopausal breast cancer. However, the TaqI polymorphism was associated with a significantly increased risk for oestrogen receptor positive tumours (OR = 1.18, 95% confidence interval [CI] = 1.00 to 1.38, comparing t allele carriers with noncarriers) but not for oestrogen receptor negative tumours (OR = 0.88, 95% CI = 0.69 to 1.13; P for interaction = 0.04). Haplotype analysis revealed the haplotype FtCA (FokI F, TaqI t, VDR-5132 C, Cdx2 A), which contains the TaqI t allele, to be associated with a significantly greater breast cancer risk as compared with the most frequent haplotype FTCG (OR = 1.43, 95% CI = 1.00 to 2.05). No significant interaction between VDR genotypes or haplotypes and 25(OH)D was observed.

Conclusion

Our results support potential effects of VDR polymorphisms on postmenopausal breast cancer risk and possible differential effects of receptor status of the tumour. However, further studies focusing on the influence of polymorphisms and haplotypes on VDR functionality, activity and concentration are needed.
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Metadata
Title
Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk
Authors
Sascha Abbas
Alexandra Nieters
Jakob Linseisen
Tracy Slanger
Silke Kropp
Elke Jonny Mutschelknauss
Dieter Flesch-Janys
Jenny Chang-Claude
Publication date
01-04-2008
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2008
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1994

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