Association between XRCC1 and XRCC3 Polymorphisms with Lung Cancer Risk: A Meta-Analysis from Case-Control Studies

Many studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln, Arg194Trp, Arg280His, −77T>C, and X-ray repair cross-complementing group 3 (XRCC3) T241M polymorphisms with lung cancer risk, but the results remained controversial. Hence, we performed a meta-analysis to investigate the association between lung cancer risk and XRCC1 Arg399Gln (14,156 cases and 16,667 controls from 41 studies), Arg194Trp (7,426 cases and 9,603 controls from 23 studies), Arg280His (6,211 cases and 6,763 controls from 16 studies), −77T>C (2,487 cases and 2,576 controls from 5 studies), and XRCC3 T241M (8,560 cases and 11,557 controls from 19 studies) in different inheritance models. We found that −77T>C polymorphism was associated with increased lung cancer risk (dominant model: odds ration [OR] = 1.45, 95% confidence interval [CI] = 1.27–1.66, recessive model: OR = 1.73, 95% CI = 1.14–2.62, additive model: OR = 1.91, 95% CI = 1.24–1.94) when all the eligible studies were pooled into the meta-analysis. In the stratified and sensitive analyses, significantly decreased lung cancer risk was observed in overall analysis (dominant model: OR = 0.83, 95% CI = 0.78–0.89; recessive model: OR = 0.90, 95% CI = 0.81–1.00; additive model: OR = 0.82, 95% CI = 0.74–0.92), Caucasians (dominant model: OR = 0.82, 95% CI = 0.76–0.87; recessive model: OR = 0.89, 95% CI = 0.80–0.99; additive model: OR = 0.81, 95% CI = 0.73–0.91), and hospital-based controls (dominant model: OR = 0.81, 95% CI = 0.76–0.88; recessive model: OR = 0.89, 95% CI = 0.79–1.00; additive model: OR = 0.80, 95% CI = 0.71–0.90) for XRCC3 T241M. In conclusion, this meta-analysis indicates that XRCC1 −77T>C shows an increased lung cancer risk and XRCC3 T241M polymorphism is associated with decreased lung cancer risk, especially in Caucasians.

已有多项研究报道了X射线修复交叉互补蛋白1组（X-ray repair cross-complementing group 1, XRCC1）的Arg399Gln、Arg194Trp、Arg280His、−77T>C位点多态性，以及X射线修复交叉互补蛋白3组（X-ray repair cross-complementing group 3, XRCC3）的T241M位点多态性与肺癌风险的关联，但相关研究结论尚存争议。为此，本研究开展一项荟萃分析，以探究不同遗传模型下，肺癌风险与XRCC1 Arg399Gln（纳入41项研究，共14156例病例、16667例对照）、Arg194Trp（纳入23项研究，共7426例病例、9603例对照）、Arg280His（纳入16项研究，共6211例病例、6763例对照）、−77T>C（纳入5项研究，共2487例病例、2576例对照）以及XRCC3 T241M（纳入19项研究，共8560例病例、11557例对照）之间的关联。荟萃分析合并所有符合纳入标准的研究后显示，−77T>C位点多态性与肺癌风险升高显著相关（显性模型：比值比[odds ratio, OR]=1.45，95%置信区间[confidence interval, CI]=1.27–1.66；隐性模型：OR=1.73，95%CI=1.14–2.62；加性模型：OR=1.91，95%CI=1.24–1.94）。针对XRCC3 T241M位点，分层及敏感性分析结果显示，在总体分析中（显性模型：OR=0.83，95%CI=0.78–0.89；隐性模型：OR=0.90，95%CI=0.81–1.00；加性模型：OR=0.82，95%CI=0.74–0.92）、高加索人群亚组中（显性模型：OR=0.82，95%CI=0.76–0.87；隐性模型：OR=0.89，95%CI=0.80–0.99；加性模型：OR=0.81，95%CI=0.73–0.91）以及以医院为基础的对照亚组中（显性模型：OR=0.81，95%CI=0.76–0.88；隐性模型：OR=0.89，95%CI=0.79–1.00；加性模型：OR=0.80，95%CI=0.71–0.90），其与肺癌风险降低显著相关。综上，本项荟萃分析表明，XRCC1 −77T>C位点多态性会增加肺癌发病风险，而XRCC3 T241M位点多态性则与肺癌风险降低相关，尤其在高加索人群中这一关联更为显著。