Department of Hematology, Peace Hospital of Changzhi Medical College, Changzhi, 046000, China.
Mol Biol Rep. 2012 Dec;39(12):11249-62. doi: 10.1007/s11033-012-2035-8. Epub 2012 Oct 12.
The previous published data on the association between the 8-oxo-guanine glycosylase-1 (OGG1) and apurinic/apyrimidinic-endonuclease-1 (APEX1/APE1) polymorphisms and lung cancer risk remained controversial. Several polymorphisms in the OGG1 and APEX1 gene have been described, including the commonly occurring Ser326Cys in OGG1 and Asp148Glu in APEX1. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 37 studies were identified to the meta-analysis, including 9,203 cases and 10,994 controls for OGG1 Ser326Cys (from 25 studies) and 3,491 cases and 4,708 controls for APEX1 Asp148Glu (from 12 studies). When all the eligible studies were pooled into the meta-analysis of OGG1 Ser326Cys polymorphism, significantly increased lung cancer risk was observed in recessive model (OR = 1.17, 95 % CI = 1.03-1.33) and in additive model (OR = 1.21, 95 % CI = 1.03-1.42). In the stratified analysis, significantly increased risk of lung cancer was also observed on the population-based studies (recessive model: OR = 1.26, 95 % CI = 1.08-1.46, additive model: OR = 1.42, 95 % CI = 1.06-1.73) and non-smokers (dominant model: OR = 1.20, 95 % CI = 1.02-1.42, recessive model: OR = 1.20, 95 % CI = 1.02-1.40, additive model: OR = 1.35, 95 % CI = 1.08-1.68). Additionally, when one study was deleted in the sensitive analysis, the results of OGG1 Ser326Cys were changed in Asians (recessive model: OR = 1.16, 95 % CI = 1.06-1.27, additive model: OR = 1.23, 95 % CI = 1.09-1.38). When all the eligible studies were pooled into the meta-analysis of APEX1 Asp148Glu polymorphism, there was no evidence of significant association between lung cancer risk and APEX1 Asp148Glu polymorphism in any genetic model. In the stratified analysis, significantly decreased lung adenocarcinoma risk was observed in recessive model (OR = 0.68, 95 % CI = 0.48-0.97, P (h) = 0.475, I(2) = 0.0 %). Additionally, when one study was deleted in the sensitive analysis, the results of APEX1 Asp148Glu were changed in Asians (recessive model: OR = 1.21, 95 % CI = 1.03-1.43) and smokers (dominant model: OR = 1.62, 95 % CI = 1.08-2.44, additive model: OR = 1.37, 95 % CI = 1.02-1.84). In summary, this meta-analysis indicates that OGG1 Ser326Cys show an increased lung cancer risk in Asians and non-smokers, APEX1 Asp148Glu polymorphism may be associated with decreased lung adenocarcinoma risk, and APEX1 Asp148Glu polymorphism show an increased lung cancer risk in Asians and smokers. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk.
先前关于 8-氧鸟嘌呤糖苷酶-1(OGG1)和脱嘌呤/脱嘧啶内切核酸酶-1(APEX1/APE1)多态性与肺癌风险之间的关联的已发表数据仍然存在争议。OGG1 和 APEX1 基因中的几个多态性已被描述,包括 OGG1 中常见的 Ser326Cys 和 APEX1 中的 Asp148Glu。本研究对文献进行了荟萃分析,以更精确地评估两者之间的关系。共确定了 37 项研究进行荟萃分析,包括 25 项研究中的 9203 例病例和 10994 例对照,以及 12 项研究中的 3491 例病例和 4708 例对照。当所有符合条件的研究都纳入到 OGG1 Ser326Cys 多态性的荟萃分析中时,发现隐性模型(OR = 1.17,95%CI = 1.03-1.33)和加性模型(OR = 1.21,95%CI = 1.03-1.42)中肺癌风险显著增加。在分层分析中,基于人群的研究(隐性模型:OR = 1.26,95%CI = 1.08-1.46,加性模型:OR = 1.42,95%CI = 1.06-1.73)和非吸烟者(显性模型:OR = 1.20,95%CI = 1.02-1.42,隐性模型:OR = 1.20,95%CI = 1.02-1.40,加性模型:OR = 1.35,95%CI = 1.08-1.68)中也观察到肺癌风险显著增加。此外,当在敏感性分析中删除一个研究时,OGG1 Ser326Cys 的结果在亚洲人群中发生了变化(隐性模型:OR = 1.16,95%CI = 1.06-1.27,加性模型:OR = 1.23,95%CI = 1.09-1.38)。当所有符合条件的研究都纳入到 APEX1 Asp148Glu 多态性的荟萃分析中时,在任何遗传模型中,都没有证据表明肺癌风险与 APEX1 Asp148Glu 多态性之间存在显著关联。在分层分析中,在隐性模型中观察到肺腺癌风险显著降低(OR = 0.68,95%CI = 0.48-0.97,P(h) = 0.475,I(2) = 0.0 %)。此外,当在敏感性分析中删除一个研究时,APEX1 Asp148Glu 的结果在亚洲人群(隐性模型:OR = 1.21,95%CI = 1.03-1.43)和吸烟者(显性模型:OR = 1.62,95%CI = 1.08-2.44,加性模型:OR = 1.37,95%CI = 1.02-1.84)中发生了变化。总之,本荟萃分析表明,OGG1 Ser326Cys 在亚洲人群和非吸烟者中与肺癌风险增加相关,APEX1 Asp148Glu 多态性可能与肺腺癌风险降低相关,APEX1 Asp148Glu 多态性在亚洲人群和吸烟者中与肺癌风险增加相关。然而,需要更大样本量的研究来进一步评估 OGG1 Ser326Cys 和 APEX1 Asp148Glu 多态性与肺癌风险的基因-环境相互作用。