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Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study.

ABSTRACT: Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk.We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TAn, 1514 cases and 1514 controls; c.454-397C --> T, 1557 cases and 1512 controls; c.454-351A --> G, 1556 cases and 1512 controls; c.729C --> T, 1562 cases and 1513 controls; c.975C --> G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data.There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A --> G or c.454-397C --> T and c.975C --> G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A --> G and c.975C --> G haplotype entailed an OR of 1.19 (95% CI 1.06-1.33) and two copies with an OR of 1.42 (95% CI 1.15-1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C --> T and c.975C --> G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant.We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.

SUBMITTER: Wedren S

PROVIDER: S-EPMC468663 | biostudies-literature | 2004

REPOSITORIES: biostudies-literature

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Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study.

Wedrén Sara S Lovmar Lovisa L Humphreys Keith K Magnusson Cecilia C Melhus Håkan H Syvänen Ann-Christine AC Kindmark Andreas A Landegren Ulf U Fermér Maria Lagerström ML Stiger Fredrik F Persson Ingemar I Baron John J Weiderpass Elisabete E

Breast cancer research : BCR 20040604 4

<h4>Introduction</h4>Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk.<h4>Methods</h4>We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ES ...[more]

PMID: 15217512

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Project description: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 [OH]D), 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 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.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.

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Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study.

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Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study.

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