Wang ZhiZhen, Zhang Wencheng
Key Laboratory of Cancer Prevention and Therapy, Department of Radiation Therapy, TianJin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Tumour Biol. 2013 Jun;34(3):1421-9. doi: 10.1007/s13277-012-0639-1. Epub 2013 Mar 17.
The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case-control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (ORMet allele vs. Thr allele=1.17, 95 % CI 0.97-1.42, P OR=0.102; ORMetMet vs. ThrThr =1.32, 95 % CI 0.93-1.87, P OR=0.121; ORThrMet vs. ThrThr =1.17, 95 % CI 0.94-1.45, P OR=0.150; ORMetMet + ThrMet vs. ThrThr =1.20, 95 % CI 0.96-1.51, P OR=0.114; ORMetMet vs. ThrThr + ThrMet =1.37, 95 % CI 0.98-1.93, P OR=0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case-control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.
X射线修复交叉互补基因3（XRCC3）是DNA修复基因家族的成员之一，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关键作用。已有研究表明，XRCC3 Thr241Met多态性与某些癌症的发生发展有关，但先前关于XRCC3 Thr241Met多态性与结直肠癌（CRC）风险之间关联的个体研究结果相互矛盾且尚无定论。为了阐明这些相互矛盾的研究结果，并增进我们对CRC发病机制的理解，我们通过汇总所有可得的出版物进行了这项更新的荟萃分析。检索了包括PubMed、Embase、Web of Science和中国知网在内的数据库以获取相关出版物。计算比值比（OR）及其相应的95%置信区间（95%CI），以评估XRCC3 Thr241Met多态性与CRC风险之间关联的强度。总共纳入了15项病例对照研究，涉及4475例病例和6373例对照。总体而言，纳入研究的荟萃分析汇总OR显示，在任何遗传模型中，XRCC3 Thr241Met多态性与CRC风险均无统计学显著关联（Met等位基因与Thr等位基因相比，OR = 1.17，95%CI 0.97 - 1.42，P OR = 0.102；MetMet与ThrThr相比，OR = 1.32，95%CI 0.93 - 1.87，P OR = 0.121；ThrMet与ThrThr相比，OR = 1.
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