Association of the CHRNA3 Locus with Lung Cancer Risk and Prognosis in Chinese Han Population
Association of the CHRNA3 Locus with Lung Cancer Risk and Prognosis in Chinese Han Population
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DOI：
10.1097/jto.0b013e3181d5e447
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发表时间：
2010-05-01
影响因子：
20.4
通讯作者：
He, Lin
中科院分区：
文献类型：
--
作者：
Niu, Xiaomin;Chen, Zhiwei;He, Lin
简介：最近在高加索人中进行的全基因组关联研究显示，含有两个尼古丁乙酰胆碱受体CHRNA基因的位点的单核苷酸多态性（SNP）与肺癌风险相关。然而，报告的风险SNP在亚洲人中极为罕见。本研究旨在鉴定CHRNA 3上与肺癌易感性相关的其他变异，并探讨CHRNA 3的SNPs是否是中国汉族人群中非小细胞肺癌（NSCLC）患者的预后因素。对529例病例和567例对照进行了病例对照研究，以研究三种SNPs的关联性使用logistic回归模型分析中国汉族人群中CHRNA 3（rs3743076、rs3743078和rs3743073）与肺癌风险的关系。CHRNA 3基因多态性与122例晚期乳腺癌患者总生存期的关系根据国际肺癌研究协会推荐的肿瘤、淋巴结、转移新分期，采用考克斯多模型对IIIb和IV期NSCLC进行评价。CHRNA 3基因rs3743073的新SNP基因型为TG或GG的患者，与TT患者相比，显示肺癌风险增加（校正比值比= 1.91; 95%置信区间，1.38-2.63; p = 9.67 x 10（-5））和最差生存率（调整后的风险比= 2.35; 95%置信区间，1.05-5.26; p = 0.04）在晚期NSCLC患者中基于国际肺癌研究协会推荐的肿瘤、淋巴结、转移新分期。提示CHRNA 3基因rs3743073多态性与中国汉族人群中晚期非小细胞肺癌的发病风险和预后有关。
Introduction: Recent genome-wide association studies in Caucasians revealed association with lung cancer risk of single nucleotide polymorphisms (SNPs) in the locus containing two nicotine acetylcholine receptor CHRNA genes. However, the reported risk SNPs are extremely rare in Asians. This study sought to identify other variants on CHRNA3 associated with lung cancer susceptibility and to explore whether SNPs of CHRNA3 are of prognostic factors in patients with non-small cell lung cancer (NSCLC) in Chinese Han population.Methods: A case-control study of 529 cases and 567 controls was performed to study the association of three SNPs (rs3743076, rs3743078, and rs3743073) in CHRNA3 with lung cancer risk in Chinese Han population using logistic regression models. The relationship between CHRNA3 polymorphisms with overall survival among 122 patients with advanced stage (stage IIIb and IV) NSCLC were evaluated using Cox multiple model based on the International Association for the Study of Lung Cancer recommended tumor, node, metastasis new staging.Results: Patients with genotypes TG or GG for the novel SNP rs3743073 in CHRNA3 gene, compared with those with TT, showed an increased risk of lung cancer (adjusted odds ratio = 1.91; 95% confidence interval, 1.38-2.63; p = 9.67 x 10(-5)) and worst survival (adjusted hazard ratio = 2.35; 95% confidence interval, 1.05-5.26; p = 0.04) in patients with advanced stage NSCLC based on International Association for the Study of Lung Cancer recommended tumor, node, metastasis new staging.Conclusions: These results suggest that the rs3743073 polymorphism in CHRNA3 is predictive for lung cancer risk and prognostic in advanced stage NSCLC in Chinese Han population.