Association between the XRCC1 Arg399Gln polymorphism and risk of cancer: evidence from 297 case-control studies.
Association between the XRCC1 Arg399Gln polymorphism and risk of cancer: evidence from 297 case-control studies.
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DOI：
10.1371/journal.pone.0078071
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Song-Tao Q
中科院分区：
文献类型：
--
作者：
Yi L;Xiao-Feng H;Yun-Tao L;Hao L;Ye S;Song-Tao Q
X 射线交叉互补组 1 (XRCC1) 中的 Arg399Gln 多态性与癌症易感性有关。之前发表的关于 XRCC1 Arg399Gln 多态性与癌症风险之间关联的数据仍然存在争议。为了更精确地估计 XRCC1 Arg399Gln 多态性与总体癌症风险之间的关联，我们对 297 项病例对照研究进行了荟萃分析，其中总共纳入了 93,941 例病例和 121,480 例对照。总体而言，在任何遗传模型中都观察到癌症风险显着增加（显性模型：比值比 [OR] = 1.04，95% 置信区间 [CI] = 1.01–1.07；隐性模型：OR = 1.08，95% CI = 1.03–1.13；加性模型： OR = 1.09，95% CI = 1.04–1.14） 荟萃分析。在进一步的分层和敏感性分析中，亚洲人（显性模型：OR = 1.39，95% CI = 1.06–1.84）和印度人（显性模型：OR = 1.64，95% CI = 1.31–2.04）观察到肝细胞癌和乳腺癌风险显着升高；隐性模型：OR = 1.94，95% CI = 1.09–3.47；加性模型： OR = 2.06, 95% CI = 1.50–2.84）。这项荟萃分析表明，XRCC1 Arg399Gln 的参与是亚洲人肝细胞癌和印度人乳腺癌的遗传易感性。此外，我们的工作还指出了 Arg399Gln 关联在某些癌症类型中的重要性，例如神经胶质瘤、胃癌和口腔癌，其中至少一些导致异质性的协变量可以得到控制，以获得关于 XRCC1 Arg399Gln 多态性在癌症发展中的功能的更结论性的理解。
The Arg399Gln polymorphism in the X-ray cross-complementing group 1 (XRCC1) had been implicated in cancer susceptibility. The previous published data on the association between XRCC1 Arg399Gln polymorphism and cancer risk remained controversial. To derive a more precise estimation of the association between the XRCC1 Arg399Gln polymorphism and overall cancer risk, we performed a meta-analysis of 297 case-control studies, in which a total of 93,941 cases and 121,480 controls were included. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR] = 1.04, 95% confidence interval [CI] = 1.01–1.07; recessive model: OR = 1.08, 95% CI = 1.03–1.13; additive model: OR = 1.09, 95% CI = 1.04–1.14) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly elevated hepatocellular and breast cancers risk were observed in Asians (dominant model: OR = 1.39, 95% CI = 1.06–1.84) and in Indians (dominant model: OR = 1.64, 95% CI = 1.31–2.04; recessive model: OR = 1.94, 95% CI = 1.09–3.47; additive model: OR = 2.06, 95% CI = 1.50–2.84), respectively. This meta-analysis suggests the participation of XRCC1 Arg399Gln is a genetic susceptibility for hepatocellular cancer in Asians and breast cancer in Indians. Moreover, our work also points out the importance of new studies for Arg399Gln association in some cancer types, such as glioma, gastric cancer, and oral cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC1 Arg399Gln polymorphism in cancer development.
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