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

Breast Cancer Research

Elisabete Weiderpass⁴  John Baron³  Ingemar Persson⁵  Fredrik Stiger²  Maria Lagerström Fermér²  Ulf Landegren⁶  Andreas Kindmark²  Ann-Christine Syvänen²  Håkan Melhus²  Cecilia Magnusson¹  Keith Humphreys¹  Lovisa Lovmar²  Sara Wedrén¹ 

[1] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;Department of Medical Sciences, Uppsala University, Sweden;Dartmouth Medical School, Hanover, New Hampshire, USA;International Agency for Research on Cancer, Lyon, France;Swedish Medical Products Agency, Uppsala, Sweden;Department of Genetics and Pathology, Uppsala University, Sweden

关键词: polymorphism;    haplotype;    gene;    oestrogen receptor α;    breast cancer;   

Others  :  1118736
DOI  :  10.1186/bcr811

 received in 2004-03-05, accepted in 2004-05-11,  发布年份 2004

【 摘 要 】

Introduction

Oestrogen receptor α, 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 α gene (ESR1) are associated with breast cancer risk.

Methods

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: TA_n, 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.

Results

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.

Conclusion

We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.

【 授权许可】

   
2004 Wedrén et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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