Estrogen Receptor Gene Polymorphisms and Lung Adenocarcinoma Risk in Never-Smoking Women
Estrogen Receptor Gene Polymorphisms and Lung Adenocarcinoma Risk in Never-Smoking Women
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DOI：
10.1097/jto.0000000000000646
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发表时间：
2015-10-01
影响因子：
20.4
通讯作者：
Yang, Pan-Chyr
中科院分区：
文献类型：
--
作者：
Chen, Kuan-Yu;Hsiao, Chin-Fu;Yang, Pan-Chyr
前言：雌激素受体(ER)基因多态性与肺癌风险的相关性研究很少。本研究旨在探讨ER基因多态性与非吸烟女性肺腺癌风险的关系。方法：对532例不吸烟女性肺腺癌患者和532例健康对照进行研究。ESR1和ESR2单核苷酸多态(SNP)数据来自全基因组关联研究。使用多变量调整的Logistic回归分析，估计ESR1和ESR2单核苷酸多态与肺腺癌风险的相关性。结果：在ESR1中，共检测到7个标记SNPs。其中，rs7753153和rs985192与肺腺癌风险相关(rs7753153：优势比[OR]，1.509；95%可信区间[CI]，1.168~1.950；rs985192：OR，1.309；95%CI，1.001~1.712)。对于ESR2，只有rs3020450与肺腺癌风险相关(OR，2.110；95%CI，1.007-4.422)。未接受激素替代治疗且携带高危基因的患者患肺腺癌的风险显著高于未携带高危基因的患者(rs7753153GG：OR，2.133；95%CI，1.415~3.216；rs985192AA/AC，OR：1.752，95%CI：1.109~2.768；rs3020450AG/GG，OR：7.162，95%CI：1.608~31.9)。易感基因rs7753153(p=0.0248)和rs9479122(p=0.0251)与ESR1表达降低相关。结论：ER基因SNPs与不吸烟女性发生肺腺癌的风险相关。ER基因SNPs和HRT对肺腺癌风险的联合作用凸显了基因-环境相互作用在肺癌发生中的重要性。
Introduction: The association between estrogen receptor (ER) gene polymorphism and lung cancer risk is rarely studied. This study aimed to explore the ER gene polymorphisms associated with the lung adenocarcinoma risk in never-smoking women.Methods: This study evaluated 532 never-smoking female patients with lung adenocarcinoma and 532 healthy controls. The ESR1 and ESR2 single nucleotide polymorphism (SNP) data were retrieved from a genome-wide association study. Using a multivariate-adjusted logistic regression assay, the associations of ESR1 and ESR2 SNPs with the lung adenocarcinoma risk were estimated. Expression quantitative trait loci analysis was performed to investigate the possible functional roles of ER gene SNPs.Results: For ESR1, seven tagged SNPs were identified. Among them, rs7753153 and rs985192 were associated with lung adenocarcinoma risk (rs7753153: odds ratios [OR], 1.509; 95% confidence intervals [CI], 1.168-1.950; rs985192: OR, 1.309; 95% CI, 1.001-1.712). For ESR2, only rs3020450 was associated with lung adenocarcinoma risk (OR, 2.110; 95% CI, 1.007-4.422). Subjects without hormone replacement therapy (HRT) use carrying at-risk genotypes had a significantly higher lung adenocarcinoma risk than subjects with HRT carrying no at-risk genotypes (rs7753153 GG: OR, 2.133; 95% CI, 1.415-3.216; rs985192 AA/AC, OR: 1.752, 95% CI: 1.109-2.768; rs3020450 AG/GG, OR: 7.162, 95% CI: 1.608-31.90). Risk genotypes of rs7753153 (p = 0.0248) and rs9479122 (p = 0.0251) were associated with decreased ESR1 expression.Conclusions: ER gene SNPs are associated with lung adenocarcinoma risk in never-smoking women. The joint effects of ER gene SNPs and HRT use on lung adenocarcinoma risk highlight the importance of the gene-environment interaction in lung carcinogenesis.