【作者】 梅朝蓉；

【导师】 周清华； 陈军； 马力；

【作者基本信息】 天津医科大学 ， 肿瘤学， 2010， 博士

【摘要】 在所有癌症中,肺癌导致死亡人数最多。来自外源性环境有害物质暴露或内源性原因的各种损伤可能导致癌发生.多种DNA修复基因存在单核苷酸多态性。因此深入探讨DNA修复基因多态性与肺癌易感性之间的关系是十分必要的。我们的研究首先针对两个重要修复通路BER途径的核心基因XRCC1和NER途径的3个核心基因XPA,XPC和XPD,参考HapMap数据库中提供的中国人的数据,运用连锁不平衡分析挑选了13个标签SNPs,采用病例-对照方法,用Taqman探针基因分型技术检测了251例肺癌患者和301例性别,年龄匹配的健康对照的上述标签SNPs的基因型,最终成功获得11个标签SNPs的分型数据。从单个SNP位点,多个SNP位点联合,单个基因的多个SNP位点组成的单体型多方面考察了DNA基因变异与肺癌遗传易感性的关系。另外,还研究了多个位点之间,位点与吸烟暴露之间的交互作用对肺癌发生的作用。推断了肺癌的风险预测模型。其次针对NER途径的3个核心基因XPA,XPC,XPD的6个常见潜在功能性位点与肺癌的相关性作了Meta分析。本研究观察到：1、XRCC1基因rs25487位点GG, AG，AA基因型在肺癌组和对照组中分布频率分别为56.6%、37.8%、5.6%和48.2%、41.9%、10.0%。分布频率在两组间比较无显著性差异(P=0.057)。2、≥60y者,携带rs25487 AG基因型及A基因型的个体较携带GG基因型的个体患肺癌风险分别降低48%和47%(95%CI:0.288-0.922,P=0.026; 95% CI:0.308-0.917, P=0.023.respectively)。3、XRCC1基因rs1799787位点CC, CT, TT基因型在肺癌组和对照组中分布频率分别为55.0%、35.9%、9.2%和51.5%、39.5%、9.0%。分布频率在两组间比较无显著性差异(P=0.668)。4、XRCC1基因rs3213334位点CC, CT, TT基因型在肺癌组和对照组中分布频率分别为82.1%、17.5%、0.4%和80.7%、18.3%、1.0%。分布频率在两组间比较无显著性差异(P=0.687)。5、XRCC1(rs25487-rs1799782-rs3213334)最常见的单体型是ACC,其次是GCC和GTC。6、XRCC1(rs25487-rs1799782-rs3213334)单体型ACC, GCC,GTC和其他型在肺癌组和对照组中分布频率分别是24.3%、39,4%、26.9%、9.4%和30.7%、30.6%、、26.9%、10.3%。分布频率在两组间比较有显著性差异(P=0.013)。7、携带XRCC1基因GCC单体型的个体较携带XRCC1基因ACC单体型的个体肺癌的风险增加63%(95%CI：1.17-2.28；P=0.004)。8、XPA基因rs2808668位点CC, CT, TT基因型在肺癌组和对照组中分布频率分别为19.5%、56.6%、23.9%和30.9%、46.2%、22.9%。分布频率在两组间比较有显著性差异(P=0.007)。9、携带rs2808668 CT基因型及T基因的个体比携带CC基因型的个体肺癌风险分别增加77%和66%(95%CI:1.12-2.80. P=0.014; 95%CI:1.08-2.55. P=0.022 respectively)。10、携带rs2808668 CT基因型及T基因的个体较携带CC基因型的个体肺鳞癌风险分别增加1.11倍和1.086倍(95%CI:1.065-4.179; P=0.032; 95%CI: 1.085-4.013,P=0.028. respectively)。11、<60y者,携带rs2808668 CT, TT基因型及T基因的个体肺癌较携带CC基因型的个体肺癌风险分别升高1.26倍,1.18倍及1.23倍(95%CI:1.184-4.298; P=0.013; 95%CI:1.010-4.709;P=0.047; 95%CI:1.210-4.119;P=0.01 respectively).12、男性中,携带rs2808668 CT基因型的个体较携带CC基因型的个体患肺癌风险增加76%(95%CI：1.014-3.063,P=0.044)。13、不吸烟者中,携带rs2808668 CT, TT基因型及T基因的个体肺癌较携带CC基因型的个体肺癌风险分别升高1.23倍,1.03倍及1.17倍(95%CI: 1.153-4.320; P=0.017; 95%CI:0.942-4.384; P=0.071; 95%CI:1.156-4.058,P=0.016. respectively)。14、XPA基因rs3176720位点AA,AC,CC基因型在肺癌组和对照组中分布频率分别为80.5%、19.1%、0.4%和83.1%、15.9%、1.0%。分布频率在两组间比较无显著性差异(P=0.613)。15、肺癌病人中XPA (rs3176720-rs2808668)最常见单体型是AC,其次是AT, CT。16、XPA (rs3176720-rs2808668)单体型AC, AT, CT在肺癌组和对照组中分布频率分别是47.8%、42.2%、10.0%和54.0% 37.0%、9.0%。分布频率在两组间比较无显著性差异(P=0.123)。17、XPC基因rs2733533位点CC, AC, AA基因型在肺癌组和对照组中分布频率分别为85.7%、14.3%、0.0%和94.0%、6.0%、0.0%。分布频率在两组间比较有显著性差异(P=0.001)。18、携带rs2733533 A基因的个体较携带CC基因型的个体患肺癌风险增加1.48倍(95%CI：1.29-4.76；P=0.006)。19、携带rs2733533 A基因的个体较携带CC基因型的个体患肺鳞癌风险增加1.61倍(95%CI：1.144-5.965,P=0.023)。20、<60y者,携带rs2733533 A基因的个体较携带CC基因型的个体肺癌风险增加5.44倍(95%CI：2.127-19.518：P=0.001)。21、男性中,携带rs2733533 A基因的个体较携带CC基因型的个体肺癌风险增加1.72倍(95%CI：1.244-5.967,P=0.012)。22、不吸烟者中,携带rs2733533 A基因的个体较携带CC基因型的个体肺癌风险增加4.8倍(95%CI：1.721-19.546；P=0.0051。23、XPC基因rs2228001位点,AA, AC, CC基因型在肺癌组和对照组中分布频率分别为38.2%、46.2%、15.5%和37.5%、45.5%、16.9%。分布频率在两组间比较无显著性差异(P=0.906)。24、XPC基因rs2229090位点,CC, CG, GG基因型在肺癌组和对照组中分布频率分别为46.2%、43.4%、10.4%和50.5%、37.9%、11.9%。分布频率在两组间比较无显著性差异(P=0.415)。25、女性中,携带rs2229090 CG基因型的个体较携带CC基因型的个体肺癌风险增加1.72倍(95%CI：1.334-5.536,P=0.006)。26.XPC基因rs3729584位点,GG,GA,AA基因型在肺癌组和对照组中分布频率分别为53.8%、38.2%、8.0%和48.8%、41.9%、9.3%。分布频率在两组间比较无显著性差异(P=0.501)。27、女性中,携带rs3729584 AG基因型及A等位基因的个体较携带GG基因型的个体肺癌风险分别降低63%和65%(95%CI:0.178-0.773,P=0.008; 95% CI:0.175-0.707, P=0.003, respectively).28、XPC(rs2229090-rs2228001-rs2733533-rs3729584)最常见单体型是CCCG,其次是CACA,GACG。29、XPC (rs2229090-rs2228001-rs2733533-rs3729584)单体型CCCG, CACA, GACG和其他型在肺癌组和对照组中分布频率分别是34.1%、26.9%、26.7%、12.4%和35.0%、30.1%、、25.9%、9.0%。分布频率在两组间比较无显著性差异(P=0.253)。30、XPD基因rs238415位点,CC, CG, GG基因型在肺癌组和对照组中分布频率分别为30.3%、50.6%、19.1%和29.9%、45.8%、24.3%。分布频率在两组间比较无显著性差异(P=0.318)。31、携带rs238415GG基因型的个体较携带CC基因型的个体肺鳞癌风险降低54%(95%CI：0.221-0.964,P=0.04)。32、XPD基因rs1799787位点,CC, CT, TT基因型在肺癌组和对照组中分布频率分别为80.9%、18.7%、0.4%和86.4%、12.3%、1.3%。分布频率在两组间比较无显著性差异(P=0.08)。33、携带rs 1799787 CT基因型的个体较携带CC基因型个体肺癌风险增加89%(95%CI：1.13-3.15.P=0.015)。34、男性中,携带rs 1799787 CT基因型的个体较携带CC基因型个体肺癌风险增加89%(95%CI：1.008-3.551,P=0.047)。35、轻度吸烟者(<30PY)中,携带rs1799787 CT基因型的个体较携带CC基因型个体肺癌风险增加1.87倍(95%CI：1.036-7.970,P=0.043)。36、XPD(rs1799787-rs238415)最常见的单体型是CG, CC和TC。37、XPD(rs1799787-rs238415)单体型CG, CC, TC在肺癌组和对照组中分布频率分别是44.4%、45.8%、9.8%和47.2%、45.3%、、7.5%。分布频率在两组间比较无有显著性差异(P=0.342)。38、与同时携带XPArs2808668CC基因型,XPCrs2733533 CC基因型,XPDrs1799787 CC基因型者比较,同时携带XPArs2808668T基因,XPCrs2733533A基因,XPDrs1799787 T基因者患肺癌风险增加9.8倍。但经过Bonferroni校正,为接近有统计学意义(95%CI：1.83-63.70.P=0.009)。39、XPCrs2733533和吸烟组成的最佳两因子预测模型是预测肺癌风险的最佳预测模型。40、重度吸烟(≥30PY)并携带XPC基因rs2733533 CC基因型的个体较不吸烟并携带CC基因型的个体患肺癌风险增加6.63倍(95%CI：4.50-12.9,P<0.001)。不吸烟并携带rs2733533 A基因的个体较患不吸烟并携带CC基因型的个体肺癌风险增加4.8倍(95%CI：1.72-19.55,P=0.005)。重度吸烟(≥30PY)并携带rs2733533 A基因的个体较不吸烟并携带CC基因型的个体患肺癌风险增加13.32倍(95%CI：4.46-45.93；P<0.001)。41、交互作用树状图显示吸烟及XRCC1基因的rs1799782位点,XPA基因的rs3176720位点,XPC基因的rs2733533,rs2228001位点,XPD基因的rs238415位点显示了它们对于肺癌发生的交互作用。XPArs3176720和XPCrs2733533之间为冗余作用或没有交互作用。但XPArs3176720和XPCrs2733533两个位点分别和XRCC1rs1799782, XPCrs2228001,XPDrs238415和吸烟状态这些因子之间均存在交互作用。由树状图可以得出,包括XRCC1,XPA, XPC, XPD基因的多个SNPs和吸烟暴露共同作用促成肺癌发生的风险。42、Meta分析显示,对于XPC A939C位点,在总体人群,CC基因型携带者肺癌风险在CC vs CA+AA, CC vs AA, CCvsCA遗传模型下分别升高23%,21%,25%。在亚洲人群中,该位点与肺癌风险无关。43、Meta分析显示,对于XPD A751C位点,在总体人群,CC基因型携带者肺癌风险在CCvsCA+AA,CA+CCvsAA,CCvsAA,CCvsCA,CvsA模型下分别升高20%,10%,25%,17%,10%。在高加索人群,CC基因型携带者及C等位基因携带者肺癌风险在CCvsCA+AA,CA+CCvsAA,CCvsAA,CCvsCA, CvsA模型下分别升高19%,12%,24%,15%,11%。在亚洲人群及非洲裔美国人中,该位点与肺癌风险无关。44、Meta分析显示,对于XPD G312A位点,在总体人群,AA基因型携带者在AAvsAG+GG, AAvsGG, AAvsAG模型下肺癌风险分别升高20%,19%,22%。在亚洲人群,AA基因型携带者在AAvsAG+GG, AAvsGG, AAvsAG模型下肺癌风险分别升高6.66倍,6.68倍,6.51倍。在高加索人群中,AA基因型携带者在AAvsAG+GG, AAvsAG模型下肺癌风险分别升高15%,17%。45、XPA G23A, XPC C499T, XPD C156A多态位点和肺癌风险无相关。结论：(1)不同DNA修复基因多态性与肺癌易感性高低不同,其中XRCC1基因(rs25487-rs1799782-rs3213334)GCC单体型、XPArs2808668CT基因型和T等位基因、XPC基因rs2733533位点A等位基因、XPD基因rs1799787位点CT基因型增加肺癌风险。(2) XRCC1,XPA,XPC,XPD基因SNPs和吸烟暴露与肺癌发生中具有交互作用；(3) Meta分析显示：XPC A939C位点CC基因型增加总体人群肺癌风险;XPD A751C位点CC基因型及C基因增加总体人群,高加索人群肺癌风险；XPD G312A位点AA基因型增加总体人群,亚洲人群和高加索人群患肺癌风险。更多还原

【Abstract】 Lung cancer is the leading cause of death in all kinds of cancers. All kinds of damages such as from exposure to exogenous environmental xenobiotics and to endogenous damage may result in an early event in Carcinogenesis. Most of DNA repair genes have single nucleotide polymorphisms. It is necessary to evaluate the relationship between the polymorphisms of DNA repair gene and the susceptibility of lung cancer. In this study, to comprehensively examined the roles of the polymorphisms of the key gene XRCC1 in the BER pathway and the roles of the polymorphisms of three core genes XPA, XPC and XPD in the NER pathway in the development of lung cancer. At first, we performed a case-control study of 251 lung cancer cases and 301 age and sex frequency-matched healthy controls. We selected 13 tagSNPs on the base of the data from Han Chinese in Beijing provided by the HapMap database and the linkage disequilibrium(LD) analysis. The tagSNPs was genotyped using Taqman platform. We successfully got genotype data of 11 tagSNPs and examined the single, joint and interactional effects between these polymorphisms and smoking on lung cancer susceptibility. We also inferred the haplotype of above four genes and evaluated the association between these haplotypes and lung cancer risk. Secondly, a variety of studies have been performed to investigate the association between the potential functional SNPs of NER genes and lung cancer risk. However, the investigations did not provide consistent results. We conduct a meta-analysis for 6 commonly studied SNPs of XPA G23A, XPC C499T, C499T, XPD A751C, G312A and C156A. The results in this study showed as follows:1. The frequency of XRCC1 rs25487 genotype GG, AG, AA in lung cancer group and control group were 56.6%、37.8%、5.6%and 48.2%、41.9%、10.0%, respectivvely. No significant differences in rs25487 genotype distributions were found between the two groups((P=0.057).2. Compared with individuals with XRCC1 rs25487 GG genotype, individuals with AG genotype and A allele showed a significant decrease of risk in individuals who older than 60 years old (adOR=0.515,95%CI:0.288-0.922, P=0.026; adOR=0.531,95%CI:0.308-0.917, P=0.023.respectively).3. The frequency of XRCC1 rs 1799787 genotype CC, CT, TT in lung cancer group and control group were 55.0%、35.9%、9.2%and 51.5%、39.5%、9.0%, respectively. No significant differences in rs25487 genotype distributions were found between the two groups((P=0.668).4. The frequency of XRCC1 rs3213334 genotype CC, CT, TT in lung cancer group and control group were 82.1%、17.5%、0.4% and 80.7%、18.3%、1.0%, respectively. No significant differences in rs25487 genotype distributions were found between the two groups((P=0.687).5. The most common haplotypes of XRCC1(rs25487-rs1799782-rs3213334) were ACC, GCC and GTC。6. The frequency of XRCCl(rs25487-rsl799782-rs3213334) haplotype ACC, GCC, GTC and the others in lung cancer group and control group were 24.3%、39.4 %、26.9%、9.4% and 30.1%、30.6%、、26.9%、10.3%,respectively. A highly significant differences in XRCC1(rs25487-rsl799782-rs3213334) haplotype distributions were found between the two groups((P=0.013).7. Use the most common haplotype XRCC1ACC as reference, haplotype GCC was associated with a increased risk of lung cancer(adjusted OR,1.63; 95%CI: 1.17-2.28; P=0.004).8. The frequency of XPA rs2808668 genotype CC, CT, TT in lung cancer group and control group were19.5%、56.6%、23.9% and 30.9%、46.2%、22.9%, respectively. A highly significant differences in rs2808668 genotype distributions were found between the two groups(P=0.007).9. Compared with individuals with CC genotype, individuals with rs2808668 CT genotype and T allele had a significant increase of lung cancer risk(adjusted OR=1.77; 95%CI:1.12-2.80. P=0.014; adjusted OR-1.66; 95%CI:1.08-2.55. P=0.022 respectively).10. Compared with individuals with CC genotype, individuals with rs2808668 CT genotype and T allele had a significant increase in risk of squamous cancer (ad OR= 2.110,95%CI:1.065-4.179; P=0.032; ad OR= 2.086,95%CI:1.085-4.013, P=0.028.respectively)11. Compared with individuals with rs2808668 CC genotype, individuals with CT, TT genotype and T allele showed a significant increase of lung cancer risk in individuals who younger than 60 years old (adOR=2.255;95%CI:1.184-4.298; P= 0.013. adOR=2.181;9,95%CI:1.010-4.709;P=0.047. adOR=2.233,95% CI:1.210-4.119;P=0.01 respectively)12. Compared with individuals with rs2808668 CC genotype, individuals with CT genotype showed a significant increase of lung cancer risk in male (adOR=l.763, 95%CI:1.014-3.063, P=0.044).13. Compared with individuals with rs2808668 CC genotype, individuals with CT, TT genotype and T allele showed a significant increase of lung cancer risk in non-smokers (ad OR= 2.232,95%CI:1.153-4.320; P=0.017;ad OR= 2.032,95%CI: 0.942-4.384; P=0.071;ad OR= 2.166,95%CI:1.156-4.058, P=0.016. respectively)14. The frequency of XPA rs3176720 genotype AA, AC, CC in lung cancer group and control group were 80.5%、9.1%、0.4% and 83.1%、15.9%、1.0%, respectively. No significant differences in rs3176720 genotype distributions were found between the two groups(P=0.613).15. The most common haplotypes of XPA (rs3176720-rs2808668) were AC, AT and CT。16. The frequency of XPA(rs3176720-rs2808668)haplotype AC, AT, CT in lung cancer group and control group were 47.8%、42.2%、10.0% and 54.0% 37.0%、9.0%,respectively. No significant differences in XPA (rs3176720-rs2808668) haplotype distributions were found between the two groups((P=0.123).17. The frequency of XPC rs2733533 genotype CC, AC, AA in lung cancer group and control group were 85.7%、14.3%、0.0%、和94.0%、6.0%、0.0%, respectively. A highly significant differences in rs2733533 genotype distributions were found between the two groups(P=0.001). 18. Compared with individuals with rs2733533 CC genotype, individuals with rs2733533 A allele showed a significant increase of lung cancer risk(adjusted OR=2.48; 95%CI:1.29-4.76; P=0.006).19. Compared with individuals with rs2733533 CC genotype, individuals with A allele showed a significant increase of squamous cancer risk(ad OR= 2.612,95%CI: 1.144-5.965, P=0.023).20. Compared with individuals with rs2733533 CC genotype, individuals with A allele showed a significant increase of lung cancer risk in younger than 60 years old ad OR=6.444,95% CI:2.127-19.518; P=0.001)21. Compared with individuals with rs2733533 CC genotype, individuals with A allele showed a significant increase of lung cancer risk in male (ad OR=2.724, 95%CI:1.244-5.967, P=0.012).22. Compared with individuals with rs2733533 CC genotype, individuals with A allele showed a significant increase of lung cancer risk in non-smokers (ad OR= 5.800,95%CI:1.721-19.546; P=0.005).23. The frequency of XPC rs2228001 genotype AA, AC, CC in lung cancer group and control group were 38.2%、46.2%、15.5% and 37.5%、45.5%、16.9%, respectively. No significant differences in rs2228001 genotype distributions were found between the two groups(P=0.906).24. The frequency of XPC rs2229090 genotype CC, CG, GG in lung cancer group and control group were 46.2%、43.4%、10.4% and 50.5%、37.9%、11.9%,respetively. No significant differences in rs2228001 genotype distributions were found between the two groups(P=0.415).25. Compared with individuals with rs2229090 CC genotype, individuals with CG genotype showed a significant increase of lung cancer risk in the female (adOR=2.718,95%CI:1.334-5.536, P=0.006).26. The frequency of XPC rs3729584 genotype GG, GA, AA in lung cancer group and control group were 53.8%、38.2%、8.0%and 48.8%、41.9%、9.3%,respectively. No significant differences in rs3729584 genotype distributions were found between the two groups(P=0.501).27. Compared with individuals with rs3729584 GG genotype, individuals with AG genotype and A allele showed a significant decrease of lung cancer risk in the female(adOR=0.370,95%CI:0.178-0.773,P=0.008; adOR=0.351,95%CI:0.175-0.707, P=0.003, respectively)28. The most common haplotypes of XPC (rs2229090-rs2228001-rs2733533-rs3729584) were CCCG, CACA and GACG.29. The frequency of XPC (rs2229090-rs2228001-rs2733533-rs3729584) haplotype CCCG, CACA, GACG and the others in lung cancer group and control group were 34.1%、26.9%、26.7%、12.4% and 35.0%、30.1%、、25.9%、9.0%,respectively. No significant differences in XPC (rs2229090-rs2228001-rs2733533-rs3729584) haplotype distributions were found between the two groups(P=0.253).30. The frequency of XPD rs238415 genotype CC, CG, GG in lung cancer group and control group were30.3%.50.6%.19.1% and 29.9%.45.8%.24.3%,respetively. No significant differences in rs238415 genotype distributions were found between the two groups(P=0.318).31. Compared with individuals with rs238415 CC genotype, individuals with GG genotype showed a significant decrease of squamous cancer risk (ad OR= 0.461,95%CI:0.221-0.964, P=0.04).32. The frequency of XPD rs 1799787 genotype CC, CT, TT in lung cancer group and control group were80.9%、18.7%、0.4% and 86.4%、12.3%、1.3%, respectively. No significant differences in rs238415 genotype distributions were found between the two groups(P=0.08).33. Compared with individuals with rs1799787 CC genotype, individuals with CT genotype showed a significant increase of lung cancer risk (adjusted OR=1.89; 95%CI:1.13-3.15.P=0.015).34. Compared with individuals with rs 1799787 CC genotype, individuals with CT genotype showed a significant increase of lung cancer risk in the male (adOR=1.892,95%CI:1.008-3.551, P=0.047).35. Compared with individuals with rs 1799787 CC genotype, individuals with CT genotype showed a significant increase of lung cancer risk in light smokers(<30PY) (ad OR= 2.873,95%CI:1.036-7.970, P=0.043). 36. The most common haplotypes of XPD(rs1799787-rs238415) were CG, CC and TC.37. The frequency of XPD(rs1799787-rs238415) haplotype CG, CC, TC in lung cancer group and control group were 44.4%、45.8%、9.8%and 47.2%、45.3%、、7.5%,respectively. No significant differences in XPD(rsl799787-rs238415) haplotype distributions were found between the two groups(P=0.342).38. Compared with individuals with XPArs2808668 CC, XPCrs2733533 CC and XPDrs1 799787 CC genotypes, individuals with XPArs2808668 A allele, XPCrs2733533 A allele and XPDrs1799787 T allele showed significant increase of lung cancer risk. But after Bonferroni adjustment, the increase was not significant(adjusted OR,10.80; 95%CI:1.83-63.70.P=0.009).39. The best two-factor model consisted of XPCrs2733533 and smoking was thoughted to be the fitted model40. Compared with non-smokers with XPC rs2733533 CC genotype, the heavy smokers (≥30PY) with rs2733533 CC genotype showed a significant increase of lung cancer risk (adjusted OR=7.63; 95%CI:4.50-12.95.P<0.001). The non-smokers with A allele showed a significant increase of lung cancer risk(adjusted OR=5.80; 95%CI:1.72-19.55.P=0.005). The heavy smokers (≥30PY) with rs2733533 A allele showed a significant increase of lung cancer risk(adjusted OR=14.32; 95%CI:4.46-45.93; P<0.001).41. Interaction dendrograms showed a visualize interaction of smoking status, XRCC1rs 1799782, XPArs3176720, XPCrs2733533, rs2228001 and XPDrs238415。XRCC1rs 1799782, XPCrs2228001, XPDrs238415 and smoking have a synergistic effects on modifying risk of lung cancer. No synergistic effect was observed between XPArs3176720 and XPCrs2733533. XPArs3176720 and XPCrs2733533 respectively have interaction with smoking status, XRCClrs1799782,, rs2228001 and XPDrs238415。SNPs of XRCC1, XPA, XPC, XPD and smoking commonly contribute to lung cancer risk.42. Meta analysis showed XPC A939C CC genotype elevated lung cancer risk was verified in total population (recessive genetic model:OR=1.23,95% CI:1.05-1.44;homozygote comparison:OR=1.21,95%CI:1.02-1.43and CC vs. CA contrast:OR=1.25,95%CI:1.06-1.48)but not in Asians.43. Meta analysis showed that both the b751C allele and CC genotype increase lung cancer risk in total population and in Caucasians. (recessive genetic model:Total population:OR=1.20,95%CI:1.07-1.35;Caucasian:OR=1.19,95%CI:1.05-1.35. dominate genetic model:Total population:OR=1.10,95%CI:1.02-1.18; Caucasian: OR=1.12,95%CI:1.02-1.23.homozygote comparison:Total population:OR=1.25,95% CI:1.11-1.42; Caucasian:OR=1.24,95%CI:1.08-1.43. CC vs. CA contrast:Total population:OR=1.17,95%CI:1.03-1.32;Caucasian:OR=1.15,95%CI:1.00-1.31 and C vs. A:Total population:OR=1.10,95%CI:1.04-1.16; Caucasian:OR=1.11,95% CI:1.04-1.18). No association was found between XPD A751C and lung cancer risk in Asians and African Americans.44.Meta analysis showed that XPD G312A AA genotype increase lung cancer risk in total population, in Asians and Caucasians(recessive genetic model:Total population:OR=1.20,95%CI:1.06-1.36; Asians:OR=7.66,95%CI:1.75-33.54; Caucasians:OR=1.15,,95%CI:1.01-1.31. homozygote comparison:Total population: OR=1.19,95%CI:1.04-1.36; Asians:OR=7.68,95%CI:1.75-33.62. AA vs. AG contrast: Total population:OR=1.22,95% CI:1.07-1.40; Asians:OR=7.51,95%CI:1.71-33.04; Caucasians:OR=1.17,95%CI:1.02-1.35).45. No significant association was found between XPA G23A, XPC C499T, XPD C156A and lung cancer risk.Conclusion:(1) Different genetic polymorphisms have different effects on lung cancer susceptibility. XRCC1 (rs25487-rs1799782-rs3213334) haplotype GCC, XPA rs2808668 CT genotype and T allele, XPC rs2733533 A allele, XPD rs1799787 CT genotype increase lung cancer susceptibility. (2) SNPs of XRCC1, XPA, XPC, XPD and smoking have interaction to increase lung cancer risk. (3)Meta analysis showed that XPC A939C CC genotype remarkably increase lung cancer risk in total population but not in Asians, that both 751C allele and CC genotype significantly increase lung cancer risk in total population and in Caucasians but not in Asians and African Americans, XPD G312A AA genotype also remarkably increase lung cancer risk in total population, Asians and Caucasians.更多还原