Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China.
Mol Biol Rep. 2012 Jan;39(1):57-69. doi: 10.1007/s11033-011-0710-9. Epub 2011 May 26.
The association of the two ERCC polymorphisms, Asp312Asn and Lys751Gln, with lung cancer risk remains controversial and inconclusive. To better evaluate the potential role of the two polymorphisms and interaction with tobacco smoking in lung cancer susceptibility presented in diverse populations, we have conducted a meta-analysis based on 26 studies from 24 publications which included analyses of Asp312Asn (7121 cases, 8962 controls) and Lys751Gln (8396 cases, 10510 controls) polymorphisms. Overall, significantly elevated lung cancer risk was associated with ERCC2 312Asn allele(homozygous model: OR=1.20[1.05-1.36], P=0.006; recessive model: OR=1.20[1.06-1.35], P=0.004) and 751Gln allele(homozygous model: OR=1.31[1.17-1.46], P<0.00001; heterozygous model: OR=1.11[1.04-1.19], P=0.003; recessive model: OR=1.23[1.11-1.37], P<0.0001; dominant model: OR=1.15[1.08-1.23], P<0.0001). In ethnic subgroup analyses, significantly increased risk was associated with ERCC2 312Asn allele for both Caucasians and Asians, and 751Gln allele for both Caucasians and Latino-Americans. When stratified by smoking status, significantly elevated risk of both polymorphisms for never-smokers was detected (dominant model, OR=1.46[1.09-1.95] and 1.57[1.19-2.08], P=0.01 and 0.002, respectively). In conclusion, this meta-analysis suggests that the two ERCC2 polymorphisms may contribute to lung cancer susceptibility serving as low-penetrance risk factors. Extremely large-scale evidence would be necessary to confirm the effects on ethnically specific populations and gene-environment interactions.
这两种 ERCC 多态性（Asp312Asn 和 Lys751Gln）与肺癌风险的关联仍然存在争议且尚无定论。为了更好地评估这两种多态性在不同人群中的潜在作用以及与吸烟的相互作用在肺癌易感性中的作用，我们进行了一项荟萃分析，该分析基于 24 篇出版物中的 26 项研究，其中包括对 Asp312Asn（7121 例病例，8962 例对照）和 Lys751Gln（8396 例病例，10510 例对照）多态性的分析。总体而言，ERCC2 312Asn 等位基因（纯合子模型：OR=1.20[1.05-1.36]，P=0.006；隐性模型：OR=1.20[1.06-1.35]，P=0.004）和 751Gln 等位基因（纯合子模型：OR=1.31[1.17-1.46]，P<0.00001；杂合子模型：OR=1.11[1.04-1.19]，P=0.003；隐性模型：OR=1.23[1.11-1.37]，P<0.0001；显性模型：OR=1.15[1.08-1.23]，P<0.0001）与肺癌风险显著升高相关。在亚组分析中，对于白种人和亚洲人，ERCC2 312Asn 等位基因与风险增加显著相关，对于白种人和拉丁裔美国人，ERCC2 751Gln 等位基因与风险增加显著相关。按吸烟状况分层时，对于从不吸烟者，这两种多态性的风险显著升高（显性模型，OR=1.46[1.09-1.95]和 1.57[1.19-2.08]，P=0.01 和 0.002）。综上所述，该荟萃分析表明，这两种 ERCC2 多态性可能与肺癌易感性有关，作为低外显率的风险因素。需要极其大规模的证据来确认对特定种族人群的影响和基因-环境相互作用。
