Common ERBB2 polymorphisms and risk of breast cancer in a white British population: a case–control study

Breast Cancer Research

Bruce AJ Ponder¹  Paul D Pharoah¹  Alison M Dunning¹  Nick E Day³  Douglas F Easton²  Mitul Shah¹  Donald M Conroy¹  Craig Luccarini¹  Fabienne Lesueur¹  Patrick R Benusiglio¹ 

[1] Department of Oncology, University of Cambridge, Strangeways Research Laboratories, Cambridge, UK;Department of Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratories, Cambridge, UK;EPIC, University of Cambridge, Strangeways Research Laboratories, Cambridge, UK

关键词: single-nucleotide polymorphism;    haplotype;    ERBB2;    case–control study;    breast cancer;   

Others  :  1114999
DOI  :  10.1186/bcr982

 received in 2004-08-17, accepted in 2004-12-01,  发布年份 2005

【 摘 要 】

Introduction

About two-thirds of the excess familial risk associated with breast cancer is still unaccounted for and may be explained by multiple weakly predisposing alleles. A gene thought to be involved in low-level predisposition to the disease is ERBB2 (HER2). This gene is involved in cell division, differentiation, and apoptosis and is frequently amplified in breast tumours. Its amplification correlates with poor prognosis. Moreover, the coding polymorphism I655V has previously been associated with an increased risk of breast cancer.

Methods

We aimed to determine if common polymorphisms (frequency ≥ 5%) in ERBB2 were associated with breast cancer risk in a white British population. Five single-nucleotide polymorphisms (SNPs) were selected for study: SNP 1 near the promoter, SNP 2 in intron 1, SNP 3 in intron 4, SNP 4 in exon 17 (I655V), and SNP 5 in exon 27 (A1170P). We tested their association with breast cancer in a large case–control study (n = 2192 cases and 2257 controls).

Results

There were no differences in genotype frequencies between cases and controls for any of the SNPs examined. To investigate the possibility that a common polymorphism not included in our study might be involved in breast cancer predisposition, we also constructed multilocus haplotypes. Our set of SNPs generated all existing (n = 6) common haplotypes and no differences were seen in haplotype frequencies between cases and controls (P = 0.44).

Conclusions

In our population, common ERBB2 polymorphisms are not involved in predisposition to breast cancer.

【 授权许可】

   
2005 Benusiglio et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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