Qu Xiao, Wang Kai, Dong Wei, Shen Hongchang, Wang Ying, Liu Qi, Du Jiajun
Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021 P.R. China.
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021 P.R. China.
Sci Rep. 2016 Feb 1;6:20149. doi: 10.1038/srep20149.
Genome-wide association studies (GWAS) have identified two CHRNA3 polymorphisms (rs578776 and rs938682) associated with lung cancer risk. Furthermore, these polymorphisms were investigated and genotyped by PCR analysis. All eligible case-control studies published up to Mar 1st 2015 were identified by searching Pubmed and Embase database. Negative association between rs578776-T allele and risk of lung cancer was obtained without obvious heterogeneity (OR: 0.83, 95% CI: 0.79-0.86; p = 0.898 for Q test). Rs938682-C allele carriers had a 12% to 28% decreased risk. Genotype model analysis showed results of dominant model for rs578776 (OR with 95% CI: 0.839(0.718-0.981)), dominant model for rs938682 (OR with 95% CI: 0.778(0.663-0.912)) and homozygous model for rs938682 (OR with 95% CI: 0.767(0.708-0.831)) were statistically significant. Subgroup analysis indicated rs578776-T variant had protective effect in Smokers, Caucasians, two histology subgroups, and two match subgroups. Meanwhile, rs938682-C allele was associated with decreased risk in Smokers, Caucasians, Lung cancer, and two match subgroups. Meta-regression suggested ethnicity might be the major source of heterogeneity in allele model and homozygous model for rs938682. Moreover, smoking status might contribute to part of heterogeneity under allele model. In summary, this meta-analysis suggested both rs578776 and rs938682 were significantly associated with the susceptibility of lung cancer.
全基因组关联研究（GWAS）已确定两个与肺癌风险相关的CHRNA3基因多态性（rs578776和rs938682）。此外，通过聚合酶链反应（PCR）分析对这些多态性进行了研究和基因分型。通过检索PubMed和Embase数据库，确定了截至2015年3月1日发表的所有符合条件的病例对照研究。rs578776-T等位基因与肺癌风险之间存在负相关，且无明显异质性（比值比：0.83，95%置信区间：0.79 - 0.86；Q检验p值 = 0.898）。携带rs938682-C等位基因者的风险降低了12%至28%。基因型模型分析显示，rs578776的显性模型（比值比及95%置信区间：0.839(0.718 - 0.981)）、rs938682的显性模型（比值比及95%置信区间：0.778(0.663 - 0.912)）以及rs938682的纯合子模型（比值比及95%置信区间：0.767(0.708 - 0.831)）具有统计学意义。亚组分析表明，rs578776-T变异在吸烟者、白种人、两个组织学亚组以及两个匹配亚组中具有保护作用。同时，rs938682-C等位基因与吸烟者、白种人及肺癌患者以及两个匹配亚组的风险降低相关。Meta回归分析表明，种族可能是rs938682等位基因模型和纯合子模型异质性的主要来源。此外，吸烟状态可能是等位基因模型下部分异质性的原因。总之，这项Meta分析表明rs578776和rs938682均与肺癌易感性显著相关。
