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Oestrogen 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.    Methods  We 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  R  2  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.    Results  The 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.    Conclusion  Our results do not support a strong association between common variants in the  ESR1  and  EGF  genes and breast cancer risk, tumour characteristics or survival.

ESR1 and EGFgenetic variation in relation to breast cancer risk and survival