Abstract
IntroductionOestrogen exposure is a central factor in the development of breast cancer. Oestrogen receptor alpha (ESR1) is the main mediator of oestrogen effect in breast epithelia and has also been shown to be activated by epidermal growth factor (EGF). We sought to determine if common genetic variation in the ESR1 and EGF genes affects breast cancer risk, tumour characteristics or breast cancer survival.MethodsWe genotyped 157 single nucleotide polymorphisms (SNPs) in ESR1 and 54 SNPs in EGF in 92 Swedish controls and selected haplotype tagging SNPs (tagSNPs) that could predict both single SNP and haplotype variation in the genes with an R2 of at least 0.8. The tagSNPs were genotyped in 1,590 breast cancer cases and 1,518 controls, and their association with breast cancer risk, tumour characteristics and survival were assessed using unconditional logistic regression models, Cox proportional hazard models and haplotype analysis.ResultsThe single tagSNP analysis did not reveal association evidence for breast cancer risk, tumour characteristics, or survival. A multi-locus analysis of five adjacent tagSNPs suggested a region in ESR1 (between rs3003925 and rs2144025) for association with breast cancer risk (p = 0.001), but the result did not withstand adjustment for multiple comparisons (p = 0.086). A similar region was also implicated by haplotype analyses, but its significance needs to be verified by follow-up analysis.ConclusionOur results do not support a strong association between common variants in the ESR1 and EGF genes and breast cancer risk, tumour characteristics or survival.
Highlights
Oestrogen exposure is a central factor in the development of breast cancer
A multi-locus analysis of five adjacent tagging single nucleotide polymorphisms (SNPs) (tagSNPs) suggested a region in ESR1 for association with breast cancer risk (p = 0.001), but the result did not withstand adjustment for multiple comparisons (p = 0.086)
Our results do not support a strong association between common variants in the ESR1 and epidermal growth factor (EGF) genes and breast cancer risk, tumour characteristics or survival
Summary
Oestrogen receptor alpha (ESR1) is the main mediator of oestrogen effect in breast epithelia and has been shown to be activated by epidermal growth factor (EGF). We sought to determine if common genetic variation in the ESR1 and EGF genes affects breast cancer risk, tumour characteristics or breast cancer survival. Oestrogen exposure is a central factor in the development and progression of this cancer [1,2,3] and its effects on the breast epithelium is primarily mediated by oestrogen receptor alpha (ESR1) [4]. One group, who genotyped 17 SNPs in the ESR1 gene, found a decreased risk of breast cancer for carriers of three common haplotypes in the gene and an EGF = epidermal growth factor; ESR1 = (o)estrogen receptor 1; HWE = Hardy-Weinberg equilibrium; LD = linkage disequilibrium; MAF = minor allele frequency; NPI = Nottingham Prognostic Index; PLEM = partition ligation expectation maximisation; SNP = single nucleotide polymorphism; tagSNP = tagging single nucleotide polymorphism; TNM = tumour, nodes, metastasis
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