Impact of ESR1 Polymorphisms on Risk of Breast Cancer in the Chinese Han Population

Abstract Purpose The Estrogen receptor-1 (ESR1) gene encodes estrogen receptor-α which is a major biomarker in the development of breast cancer. This study aimed to investigate the effect of ESR1 polymorphisms on breast cancer in Chinese Han women. Methods We genotyped four candidate single nucleotide polymorphisms (SNPs) in ESR1 among 503 breast cancer patients and 503 healthy people using Agena MassARRAY platform. The association between ESR1 polymorphisms and breast cancer risk was evaluated using odds ratio (OR) and 95% confidence intervals (95% CIs) under four genetic models. The HaploReg v4.1 and GEPIA database were used for SNP functional annotation and ESR1expression analysis respectively. Results The T allele of rs9383938 in ESR1 was significantly associated with an increased breast cancer risk (OR = 1.26, 95% CI = 1.05 – 1.50, p = 0.013). In genetic models, rs9383938 increased breast cancer risk in codominant model (OR = 1.54, 95% CI = 1.07 – 2.22, p = 0.021), dominant model (OR = 1.31, 95% CI = 1.01 – 1.68, p = 0.040), and additive model (OR = 1.24, 95% CI = 1.04 – 1.48, p = 0.017). Stratification analysis showed that rs9383938 and rs2228480 raised the breast cancer susceptibility in individuals aged younger than 52 years old. Rs1801132 of ESR1 was significantly associated with the status of ER, PR, and Her-2 in allele model and genetic models (p Conclusions This study demonstrated that ESR1 polymorphisms might influence breast cancer susceptibility in Chinese Han population. Further mechanisms studies are needed to confirm the contribution of ESR1.