ESR1 and EGF genetic variation in relation to breast cancer risk and survival

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 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.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.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.Breast cancer is the most common cancer in women overall worldwide. Oestrogen exposure is a central factor in the development and progression of this cancer [1-3] and its effects on the breast epithelium is primarily mediated by oestrogen receptor alpha (ESR1) [4]. In addition to being activated by oestrogen, the ESR1 protein can be activated by growth factors such as epidermal growth factor (EGF) [3], which acts as a potent mitogen for epithelial cells, including mammary epithelia [5]. Variation in the ESR1 (MIM 133430) and EGF (MIM 131530) genes affecting the function or expression of their respective proteins could thus potentially affect the risk of developing breast cancer, characteristics of the tumour or the risk of dying from the disease.With regard to breast cancer risk or survival, a number of single nu