Tian Xin, Tian Ye, Ma Ping, Sui Chengguang, Meng Fandong, Li Yan, Fu Liye, Jiang Tao, Wang Yang, Jiang Youhong
Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Shenyang, 110001, China.
Tumour Biol. 2013 Oct;34(5):2589-97. doi: 10.1007/s13277-013-0806-z. Epub 2013 Jun 8.
X-ray repair cross-complementing group 3 (XRCC3) plays a vital role in maintaining the stability of genome by homologous recombination repair for DNA double-strand breaks. The genetic polymorphism of XRCC3 C241T has been implicated in lung cancer risk, but the findings across published studies in Asians are inconsistent and inconclusive. To estimate the precise association of XRCC3 C241T polymorphism with lung cancer risk, a meta-analysis of all currently available studies in Asians was performed. A comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases was conducted for eligible studies based on the inclusion criteria. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to assess the association. Besides, subgroup analysis and sensitivity analysis were also performed for further estimation. Seven available studies with a total of 7,398 subjects were finally included into this meta-analysis. The overall ORs indicated that the XRCC3 C241T polymorphism was not associated with a lung cancer risk among Asians in all genetic contrast modes (ORT allele vs. C allele = 1.08, 95 % CI 0.95-1.24, P OR = 0.252; ORTT vs. CC = 1.30, 95 % CI 0.69-2.45, P OR = 0.426; ORCT vs. CC = 1.07, 95 % CI 0.93-1.24, P OR = 0.363; ORTT + CT vs. CC = 1.08, 95 % CI 0.94-1.24, P OR = 0.300; ORTT vs. CC + CT = 1.29, 95 % CI 0.68-2.43, P OR = 0.439). We failed to identify significant association between the XRCC3 C241T polymorphism and risk of lung cancer in Chinese and population-based studies. Interestingly, the pooled ORs in hospital-based studies indicated that the XRCC3 C241T variant carriers were more susceptible to lung cancer (ORT allele vs. C allele = 1.27, 95 % CI 1.04-1.56, P OR = 0.019; ORCT vs. CC = 1.26, 95 % CI 1.01-1.57, P OR = 0.045; ORTT + CT vs. CC = 1.28, 95 % CI 1.03-1.59, P OR = 0.027). Sensitivity analysis confirmed the stability and liability of all results. This meta-analysis suggests that the XRCC3 C241T polymorphism may not exert a risk effect on the lung cancer risk in Asians, although a statistically significant association was observed among the hospital-based studies. Thus, the precise relationship between the XRCC3 C241T variant and lung cancer risk needs further confirmation in future studies with large available data.
X射线修复交叉互补基因3（XRCC3）通过DNA双链断裂的同源重组修复在维持基因组稳定性方面发挥着至关重要的作用。XRCC3 C241T的基因多态性与肺癌风险有关，但亚洲已发表研究的结果并不一致且尚无定论。为了评估XRCC3 C241T多态性与肺癌风险的确切关联，我们对亚洲人目前所有可用的研究进行了荟萃分析。根据纳入标准，对PubMed、Embase、Web of Science和中国国家知识基础设施数据库进行了全面检索，以查找符合条件的研究。计算合并比值比（OR）及相应的95%置信区间（CI）以评估关联。此外，还进行了亚组分析和敏感性分析以进一步评估。最终，七项共有7398名受试者的可用研究被纳入该荟萃分析。总体OR表明，在所有基因对比模式下，XRCC3 C241T多态性与亚洲人的肺癌风险无关（OR T等位基因vs. C等位基因 = 1.08，95%CI 0.95 - 1.24，P OR = 0.252；OR TT vs. CC = 1.30，95%CI 0.69 - 2.45，P OR = 0.426；OR CT vs. CC = 1.07，95%CI 0.93 - 1.24，P OR = 0.363；OR TT + CT vs. CC = 1.08，95%CI 0.94 - 1.24，P OR = 0.300；OR TT vs. CC + CT = 1.29，95%CI 0.68 - 2.43，P OR = （此处原文有误，应为0.439））。我们未能在中国人群和基于人群的研究中发现XRCC3 C241T多态性与肺癌风险之间的显著关联。有趣的是，基于医院的研究中的合并OR表明，XRCC3 C241T变异携带者更易患肺癌（OR T等位基因vs. C等位基因 = 1.27，95%CI 1.04 - 1.56，P OR = 0.019；OR CT vs. CC = 1.26，95%CI 1.01 - 1.57，P OR =
（此处原文有误，应为0.045）；OR TT + CT vs. CC = 1.28，95%CI 1.03 - 1.59，P OR = 0.027）。敏感性分析证实了所有结果的稳定性和可靠性。该荟萃分析表明，XRCC3 C241T多态性可能不会对亚洲人的肺癌风险产生风险影响，尽管在基于医院的研究中观察到了统计学上的显著关联。因此，XRCC3 C241T变异与肺癌风险之间的确切关系需要在未来有大量可用数据的研究中进一步证实。
