Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China.
Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China.
Clin Breast Cancer. 2021 Jun;21(3):e235-e242. doi: 10.1016/j.clbc.2020.10.003. Epub 2020 Oct 16.
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.
We genotyped 4 candidate single nucleotide polymorphisms (SNPs) in ESR1 among 503 patients with breast cancer and 503 healthy people using the Agena MassARRAY platform. The association between ESR1 polymorphisms and breast cancer risk was evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) under 4 genetic models. The HaploReg v4.1 and GEPIA database were used for SNP functional annotation and ESR1 expression analysis, respectively.
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 = .013). In genetic models, rs9383938 increased breast cancer risk in the codominant model (OR, 1.54; 95% CI, 1.07-2.22; P = .021), the dominant model (OR, 1.31; 95% CI, 1.01-1.68; P = .040), and the additive model (OR, 1.24; 95% CI, 1.04-1.48; P = .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 estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 in the allele model and genetic models (P < .05).
This study demonstrated that ESR1 polymorphisms might influence breast cancer susceptibility in the Chinese Han population. Further mechanism studies are needed to confirm the contribution of ESR1.
雌激素受体 1（ESR1）基因编码雌激素受体-α，是乳腺癌发生的主要生物标志物。本研究旨在探讨 ESR1 多态性对中国汉族女性乳腺癌的影响。
我们采用 Agena MassARRAY 平台，对 503 例乳腺癌患者和 503 例健康对照者的 ESR1 中 4 个候选单核苷酸多态性（SNP）进行基因分型。采用优势比（OR）及其 95%置信区间（95%CI）在 4 种遗传模型下评估 ESR1 多态性与乳腺癌风险的关系。采用 HaploReg v4.1 和 GEPIA 数据库分别对 SNP 功能注释和 ESR1 表达进行分析。
ESR1 中的 rs9383938 等位基因 T 与乳腺癌风险增加显著相关（OR，1.26；95%CI，1.05-1.50；P=0.013）。在遗传模型中，rs9383938 在共显性模型（OR，1.54；95%CI，1.07-2.22；P=0.021）、显性模型（OR，1.31；95%CI，1.01-1.68；P=0.040）和加性模型（OR，1.24；95%CI，1.04-1.48；P=0.017）中增加乳腺癌风险。分层分析显示，rs9383938 和 rs2228480 增加了年龄小于 52 岁的个体的乳腺癌易感性。ESR1 的 rs1801132 在等位基因模型和遗传模型中与雌激素受体、孕激素受体和人表皮生长因子受体 2 的状态显著相关（P<0.05）。
本研究表明 ESR1 多态性可能影响中国汉族人群的乳腺癌易感性。需要进一步的机制研究来确认 ESR1 的作用。
