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Breast Cancer Research

, 10:R31

First Online: 17 April 2008Received: 21 December 2007Revised: 21 February 2008

Abstract

IntroductionVitamin 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 OHD, the biomarker for vitamin D status in humans, has rarely been examined.

MethodsWe 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.

ResultsNo differences in serum 25ODD 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 25OHD was observed.

ConclusionOur 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.

Abbreviations125OH2D = 1,25-dihydroxyvitamin D

25OHD25-hydroxyvitamin D

CIconfidence interval

ERoestrogen receptor

HWEHardy-Weinberg equilibrium

NHSNurses Health Study

ORodds ratio

PCRpolymerase chain reaction

PRprogesterone receptor

R-N-KRhein-Neckar-Karlsruhe

SNPsingle nucleotide polymorphism

VDRvitamin D receptor.

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Autor: Sascha Abbas - Alexandra Nieters - Jakob Linseisen - Tracy Slanger - Silke Kropp - Elke Jonny Mutschelknauss - Dieter Fles

Fuente: https://link.springer.com/



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