title: Validation of associations between ESR1 variants and breast cancer risk in Chinese cohorts.
abstract: Estrogen receptor-a (ER) protein plays a key role in breast carcinogenesis, and common genetic variants in the corresponding gene locus have been associated with breast cancer risk in different populations. Here, we analyzed estrogen receptor 1 (ESR1) associations in two hospital-based studies of patients from the south of China. Three single-nucleotide polymorphisms (SNPs; rs3757318, rs2046210, and rs3734805) in ESR1 were selected from previous genome-wide association study results and were genotyped using the Sequenom MassARRAY® iPLEX System in 845 breast cancer patients and 882 healthy controls. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Stratified analyses according to the status of ER and progesterone receptor (PR) were also performed. Of the three SNPs, rs3757318 did not pass the Hardy-Weinberg equilibrium test and was excluded from the subsequent analysis. The other two SNPs (rs2046210 and rs3734805) were strongly associated with susceptibility to breast cancer. Allele T of rs2046210 and allele C of rs3734805 were risk alleles and the adjusted ORs were 1.348 (95%CI = 1.172-1.550, P = 0.0001) and 1.319 (95%CI = 1.144-1.522, P = 0.0001), respectively. Furthermore, the risk allele of rs2046210 gave negative results for ER and PR expression in an immunohistochemical test, with ORs of 0.602 (95%CI = 0.384-0.944, P = 0.027) and 0.532 (95%CI = 0.338-0.837, P = 0.006), respectively. Our study further supports associations between rs2046210 and rs3734805 and breast cancer risk in Chinese women.
authors.affiliation: Clinical Laboratory of Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Breast Cancer Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: G Y
authors.initials: GY
authors.lastname: Yao
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: F X
authors.initials: FX
authors.lastname: Li
authors.affiliation: Clinical Laboratory of Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Y R
authors.initials: YR
authors.lastname: Qiu
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou, China yxxzb@sohu.com.
authors.forename: X X
authors.initials: XX
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha