DNA修复基因多态性与肺癌遗传易感性的相关性研究
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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。
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 model
40. 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.
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。
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 model
40. 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.
引文
[1]Gibbs R, Belmont J, Hardenbol P, et al. The international HapMap project. 2003.
[2]Schwartz A, Ruckdeschel J. Familial lung cancer:genetic susceptibility and relationship to chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine 2006; 173(1):16.
[3]Hirvonen A, Husgafvel-Pursiainen K, Anttila S, et al. The GSTM1 null genotype as a potential risk modifier for squamous cell carcinoma of the lung. Carcinogenesis 1993; 14(7):1479.
[4]Wei Q, Cheng L, Hong W, et al. Reduced DNA repair capacity in lung cancer patients. Cancer Research 1996; 56(18):4103.
[5]Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 2002; 11(12):1513-30.
[6]Spitz MR WQ, Dong Q, Amos CI, Wu X. Genetic susceptibility to lung cancer:the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev.2003 Aug;12(8):689-98.2003.
[7]Wei QY, Spitz MR. The role of DNA repair capacity in susceptibility to lung cancer:A review. Cancer and Metastasis Reviews 1997; 16(3-4):295-307.
[8]Ronen A, Glickman B. Human DNA repair genes. Environmental and Molecular Mutagenesis 2001; 37(3):241.
[9]Hoeijmakers J. DNA Damage, Aging, and Cancer. New England Journal of Medicine 2009; 361(15):1475.
[10]Tuteja N, Tuteja R. Unraveling DNA repair in human:molecular mechanisms and consequences of repair defect. Critical reviews in biochemistry and molecular biology 2001; 36(3):261.
[11]Peltomaki P. Deficient DNA mismatch repair:a common etiologic factor for colon cancer. Human Molecular Genetics 2001; 10(7):735.
[12]Schwartz AG, Prysak GM, Bock CH, et al.-The molecular epidemiology of lung cancer. Carcinogenesis 2007; 28(3):507-518.
[13]Park JY, Lee SY, Jeon HS, et al. Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 2002;11(1):23-7.
[14]Hoeijmakers J. Genome maintenance mechanisms for preventing cancer. Nature 2001; 411(6835):366-374.
[15]Braithwaite E, Wu,X. and Wang,Z.. Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts:involvement of two excision repair mechanisms in vitro. Carcinogenesis,19,1239-1246. 1998.
[16]Beernink P, Hwang M, Ramirez M, et al. Specificity of protein interactions mediated by BRCT domains of the XRCC1 DNA repair protein. Journal of Biological Chemistry 2005; 280(34):30206.
[17]Caldecott K, Aoufouchi S, Johnson P, et al. XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular'nick-sensor'in vitro. Nucleic Acids Research 1996; 24(22):4387.
[18]Masson M, Niedergang C, Schreiber V, et al. XRCC1 is specifically associated with poly (ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Molecular and Cellular Biology 1998; 18(6):3563.
[19]Whitehouse C, Taylor R, Thistlethwaite A, et al. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 2001; 104(1):107-117.
[20]Vidal AE, Boiteux, S., Hickson, I. D., and Radicella, J. P. XRCC1 coordinates the initial and late stages of DNA abasic site repair through proteinprotein interactions. EMBO J.,20:6530-6539,2001.2001.
[21]Thompson LH, West MG XRCC1 keeps DNA from getting stranded. Mutat Res 2000; 459(1):1-18.
[22]van Hoffen A, Balajee AS, van Zeeland AA, et al. Nucleotide excision repair and its interplay with transcription. Toxicology 2003; 193(1-2):79-90.
[23]de Laat WL, Jaspers NG, Hoeijmakers JH. Molecular mechanism of nucleotide excision repair. Genes Dev 1999; 13(7):768-85.
[24]L Li XL, CA Peterson and RJ Legerski. An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair. Mol. Cell. Biol,101995,5396-5402, Vol 15, No.101995.
[25]Wu X, Fan W, Xu S, et al. Sensitization to the cytotoxicity of cisplatin by transfection with nucleotide excision repair gene xeroderma pigmentosun group A antisense RNA in human lung adenocarcinoma cells. Clin Cancer Res 2003; 9(16 Pt 1):5874-9.
[26]Masutani C, Araki M, Sugasawa K, et al. Identification and characterization of XPC-binding domain of hHR23B. Molecular and Cellular Biology 1997; 17(12):6915.
[27]Araki M, Masutani C, Takemura M, et al. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. The Journal of biological chemistry 2001; 276(22):18665.
[28]Sugasawa K, Shimizu Y, Iwai S, et al. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair 2002; 1(1):95.
[29]Costa R, Chigan as V, da Silva Galhardo R, et al. The eukaryotic nucleotide excision repair pathway. Biochimie 2003; 85(11):1083-1099.
[30]D'Errico M, Parlanti E, Teson M, et al. New functions of XPC in the protection of human skin cells from oxidative damage. EMBO J 2006; 25(18):4305-15.
[31]Hollander MC, Philburn RT, Patterson AD, et al. Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 2005; 102(37):13200-13205.
[32]Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 1998; 58(4):604-8.
[33]Coin F, Bergmann E, Tremeau-Bravard A, et al. Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH. The EMBO Journal 1999; 18(5):1357.
[34]Wood RD MM, Lindahl T. Human DNA repair genes,2005. Mutat Res.2005 Sep 4;577(1-2):275-83.2005.
[35]Scagliotti G, Longo M, Novello S. Nonsmall cell lung cancer in never smokers. Current Opinion In Oncology 2009; 21(2):99.
[36]Kiyohara C, Takayama K, Nakanishi Y. Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk:a meta-analysis. Lung Cancer 2006; 54(3):267-83.
[37]Michiels S, Danoy P, Dessen P, et al. Polymorphism discovery in 62 DNA repair genes and haplotype associations with risks for lung and head and neck cancers. Carcinogenesis 2007; 28(8):1731-9.
[38]McKusick LPaVA. Dissecting Human Disease in the Postgenomic Era. Science 16 February 2001:Vol.291. no.5507, pp.1224-1229 2001.
[39]Carlson CS EM, Rieder MJ, Smith JD, Kruglyak L, Nickerson DA. Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans. Nat Genet.2003 Apr;33(4):518-21. Epub 2003 Mar 24.2003.
[40]Tapp I, Malmberg L, Rennel E, et al. Homogeneous Scoring of Single-Nucleotide Polymorphisms:Comparison of the 5'-Nuclease TaqMan^(R) Assay and Molecular Beacon Probes. Biotechniques 2000; 28(4):732-739.
[41]Livak K, Flood S, Marmaro J, et al. Oligonucleotides with fluorescent dyes at opposite ends provide a quenched probe system useful for detecting PCR product and nucleic acid hybridization. Genome Research 1995; 4(6):357.
[42]Ding K ZK, He F, Shen Y. LDA--a java-based linkage disequilibrium analyzer. Bioinformatics.2003 Nov 1;19(16):2147-8.Click here to read 2003.
[43]Zhang W, Collins A, Maniatis N, et al. Properties of linkage disequilibrium (LD) maps. Proceedings of the National Academy of Sciences 2002; 99(26):17004.
[44]Johnson G, Esposito L, Barratt B, et al. Haplotype tagging for the identification of common disease genes. Nature genetics 2001; 29(2):233-237.
[45]Stephens M SM, Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001;68:978-89.2001.
[46]Hung RJ, Hall J, Brennan P, et al. Genetic polymorphisms in the base excision repair pathway and cancer risk:a HuGE review. Am J Epidemiol 2005; 162(10):925-42.
[47]Levy N, Martz A, Bresson A, et al. XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage. Nucleic Acids Research 2006; 34(1):32.
[48]Monaco R, Rosal R, Dolan MA, et al. Conformational effects of a common codon 399 polymorphism on the BRCT1 domain of the XRCC1 protein. Protein J 2007; 26(8):541-6.
[49]Shen M, Berndt SI, Rothman N, et al. Polymorphisms in the DNA base excision repair genes APEX1 and XRCC1 and lung cancer risk in Xuan Wei, China. Anticancer Res 2005; 25(1B):537-42.
[50]Matullo G, Dunning A, Guarrera S, et al. DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis 2006; 27(5):997.
[51]Pachouri SS, Sobti RC, Kaur P, et al. Contrasting impact of DNA repair gene XRCC1 polymorphisms Arg399Gln and Arg194Trp on the risk of lung cancer in the north-Indian population. DNA Cell Biol 2007; 26(3):186-91.
[52]Jia-wei L, Li-na M, Guo-rong W. Relationship between polymorphisms of DNA repair gene XRCC1 and susceptibility to lung cancer. China Oncology.15(2005)335-338 2005.
[53]De Ruyck K, Szaumkessel M, De Rudder I, et al. Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk. Mutat Res 2007; 631(2):101-10.
[54]David-Beabes GL, London SJ. Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians. Lung Cancer 2001; 34(3):333-9.
[55]Zhang X, Miao X, Liang G, et al. Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res 2005; 65(3):722-6.
[56]Fan J, Otterlei M, Wong H, et al. XRCC1 co-localizes and physically interacts with PCNA. Nucleic Acids Research 2004; 32(7):2193.
[57]Ratnasinghe DL, Yao SX, Forman M, et al. Gene-environment interactions between the codon 194 polymorphism of XRGC1 and antioxidants influence lung cancer risk. Anticancer Res 2003; 23(1B):627-32.
[58]Vogel U, Nexo BA, Wallin H, et al. No association between base excision repair gene polymorphisms and risk of lung cancer. Biochem Genet 2004; 42(11-12):453-60.
[59]Hu Z, Ma H, Lu D, et al. A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking. Pharmacogenet Genomics 2005; 15(7):457-63.
[60]Volker M MM, Karmakar P, van Hoffen A, Schul W, Vermeulen W, Hoeijmakers JH, van Driel R, van Zeeland AA, Mullenders LH. Sequential assembly of the nucleotide excision repair factors in vivo. Mol Cell.2001 Jul;8(1):213-24.2001.
[61]Guzder SN SC, Prakash L, Prakash S. (2006). Comp lex formation with damage recognition p rotein Rad14 is essential for Saccharomyces cerevisiae Radl Rad10 nuclease to perform its function in nucleotide excision repair in vivo. Mol Cell Biol,2006,26:1135-11412006.
[62]Stout GJ, Oosten M, Acherrat FZ, et al. Selective DNA damage responses in murine Xpa-/-, Xpc-/-and Csb-/-keratinocyte cultures. DNA Repair (Amst) 2005; 4(11):1337-44.
[63]Butkiewicz D, Rusin M, Harris CC, et al. Identification of four single nucleotide polymorphisms in DNA repair genes:XPA and XPB (ERCC3) in Polish population. Hum Mutat 2000; 15(6):577-8.
[64]Kiyohara C, Yoshimasu K. Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk:a meta-analysis. Int J Med Sci 2007; 4(2):59-71.
[65]Akiri Q Nahari D, Finkelstein Y, et al. Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription. Oncogene 1998; 17(2):227-236.
[66]Miller KL, Karagas MR, Kraft P, et al. XPA, haplotypes, and risk of basal and squamous cell carcinoma. Carcinogenesis 2006; 27(8):1670-5.
[67]Park JY, Park SH, Choi JE, et al. Polymorphisms of the DNA repair gene xeroderma pigmentosum group A and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 2002; 11(10 Pt 1):993-7.
[68]Wu X, Zhao H, Wei Q, et al. XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis 2003; 24(3):505-9.
[69]Popanda O, Schattenberg T, Phong CT, et al. Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis 2004; 25(12):2433-41.
[70]Butkiewicz D, Popanda O, Risch A, et al. Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene. Cancer Epidemiol Biomarkers Prev 2004; 13(12):2242-6.
[71]Vogel U, Overvad K, Wallin H, et al. Combinations of polymorphisms in XPD, XPC and XPA in relation to risk of lung cancer. Cancer Lett 2005; 222(1):67-74.
[72]Qiao Y SM, Shen H, Guo Z, Shete S, Hedayati M, Grossman L, Mohrenweiser H, Wei Q. Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes. Carcinogenesis.2002 Feb;23(2):295-9.2002.
[73]Spitz MR, Wu X, Wang Y, et al. Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 2001; 61(4):1354-7.
[74]Misra RR, Ratnasinghe D, Tangrea JA, et al. Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland. Cancer Lett 2003; 191(2):171-8.
[75]Zienolddiny S, Campa D, Lind H, et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis 2006; 27(3):560-7.
[76]Raaschou-Nielsen O, Sorensen M, Overvad K, et al. Polymorphisms in nucleotide excision repair genes, smoking and intake of fruit and vegetables in relation to lung cancer.Lung Cancer 2008; 59(2):171-9.
[77]Francisco G, Menezes PR, Eluf-Neto J, et al. XPC polymorphisms play a role in tissue-specific carcinogenesis:a meta-analysis.Eur J Hum Genet 2008.ST.RE; 16(6):724-34.
[78]Janicijevic A SK, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst).2003 Mar 1;2(3):325-36.2003.
[79]Tapias A AJ, Forget D, Enzlin JH, Scharer OD, Coin F, Coulombe B, Egly JM. Ordered conformational changes in damaged DNA induced by nucleotide excision repair factors. J Biol Chem.2004 Apr 30;279(18):19074-83. Epub 2004 Feb 23.
[80]Melis JP, Wijnhoven SW, Beems RB, et al. Mouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes. Cancer Res 2008; 68(5):1347-53.
[81]Zhu Y YH, Chen Q, Lin J, Grossman HB, Dinney CP, Wu X, Gu J. Modulation of DNA damage/DNA repair capacity by XPC polymorphisms. DNA Repair (Amst).2008 Feb 1;7(2):141-8. Epub 2007 Oct 17 2008.
[82]Hu Z, Wang Y, Wang X, et al. DNA repair gene XPC genotypes/haplotypes and risk of lung cancer in a Chinese population. Int J Cancer 2005; 115(3):478-83.
[83]Lee GY, Jang JS, Lee SY, et al. XPC polymorphisms and lung cancer risk. Int J Cancer 2005; 115(5):807-13.
[84]Shen M, Berndt SI, Rothman N, et al. Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China. Int J Cancer 2005; 116(5):768-73.
[85]Bai Y, Xu L, Yang XB, et al. Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population:a case-control study. Bmc Cancer 2007; 7:-.
[86]Chang JS, Wrensch MR, Hansen HM, et al. Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans. Int J Cancer 2008; 123(9):2095-104.
[87]Pagani F BF. Genomic variants in exons and introns:Identifying the splicing spoilers. Nat Rev Genet 2004;5:389-96.2004.
[88]Wolfe KJ, Wickliffe JK, Hill CE, et al. Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA expression. Pharmacogenet Genomics 2007; 17(11):897-905.
[89]Palli D, Russo A, Masala G, et al. DNA adduct levels and DNA repair polymorphisms in traffic-exposed workers and a general population sample. Int J Cancer 2001; 94(1):121-7.
[90]Au WW, Salama SA, Sierra-Torres CH. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 2003;111(15):1843-50.
[91]Hou S, Falt S, Angelini S, et al. The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis 2002; 23(4):599.
[92]Yin J, Vogel U, Ma Y, et al. Polymorphism of the DNA repair gene ERCC2 Lys751Gln and risk of lung cancer in a northeastern Chinese population. Cancer Genet Cytogenet 2006; 169(1):27-32.
[93]Butkiewicz D RM, Enewold L, Shields PG, Chorazy M, Harris CC. Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis. 2001 Apr;22(4):593-7.2001.
[94]David-Beabes GL, Lunn RM, London SJ. No association between the XPD (Lys751Gln) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev 2001; 10(8):911-2.
[95]Park JY LS, Jeon HS, Park SH, Bae NC, Lee EB, Cha SI, Park JH, Kam S, Kim IS, Jung TH. Lys751Gln polymorphism in the DNA repair gene XPD and risk of primary lung cancer.. Lung Cancer.2002 Apr;36(1):15-6.2002.
[96]Chen S, Tang D, Xue K, et al. DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Carcinogenesis 2002; 23(8):1321-5.
[97]Hahn LW RM, Moore JH. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics.2003 Feb 12;19(3):376-82.2003.
[98]Ritchie MD, Hahn LW, Roodi N, et al. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 2001; 69(1):138-47.
[99]胡永华；唐李陈.多因子降维法分析基因-基因交互作用的应用进展Recent advances in applications of multifactor dimensionality reduction for detecting gene-gene interactions.2007.
[100]Moore J, Gilbert J, Tsai C, et al. A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. Journal of theoretical biology 2006;241(2):252-261.
[101]Liu Z. Smoking and lung cancer in China:combined analysis of eight case-control studies. International Journal of Epidemiology 1992; 21(2):197.
[102]Wynder E, Hoffmann D. Smoking and lung cancer:scientific challenges and opportunities. Cancer Research 1994; 54(20):5284-5294.
[103]Paul I.W. De Bakker RRG, David Altshuler, Brian E. Henderson, and, Haiman CA. Transferability of Tag SNPs to Capture Common Genetic Variation in DNA Repair Genes Across Multiple Populations. Pacific Symposium on Biocomputing 11:478-486(2006) 2006.
[104]Duell EJ, Bracci PM, Moore JH, et al.*Detecting pathway-based gene-gene and gene-environment interactions in pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2008; 17(6):1470-9.
[105]Coffey C, Hebert P, Ritchie M, et al. An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction:The importance of model validation. BMC Bioinformatics 2004; 5:49.
[106]Marylyn D. Ritchie,2 Lance W. Hahn,1,2 Nady Roodi,3 L. Renee Bailey,1,2 William D. Dupont,4 Fritz F. Parl,3 and Jason H. Moore1. Multifactor-Dimensionality Reduction Reveals High-Order Interactions among Estrogen-Metabolism Genes in Sporadic Breast Cancer. Am J Hum Genet.2001 July; 69(1):138-147 2001.
[107]Lau J, Ioannidis J, Schmid C. Quantitative synthesis in systematic reviews. Annals of Internal Medicine 1997; 127(9):820.
[108]Chu S, Callaghan W, Kim S, et al. Maternal obesity and risk of gestational diabetes mellitus. Diabetes care 2007; 30(8):2070.
[109]Higgins J, Thompson S, Deeks J, et al. Measuring inconsistency in meta-analyses. British Medical Journal 2003; 327(7414):557.
[110]Warn D, Thompson S, Spiegelhalter D. Bayesian random effects meta-analysis of trials with binary outcomes:methods for the absolute risk difference and relative risk scales.
[111]Vogel U, Laros I, Jacobsen NR, et al. Two regions in chromosome 19ql3.2-3 are associated with risk of lung cancer. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 2004; 546(1-2):65-74.
[112]Xing DY, Qi J, Tan W, et al. Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing. Ch in J M ed Genet, February 2003, Vol.20, No.1 2003; 20(l):35-8.
[113]Xing D, Tan W, Wei Q, et al. Polymorphisms of the DNA repair gene XPD and risk of lung cancer in a Chinese population. Lung Cancer 2002; 38(2):123-9.
[114]Yin JY, Li JC, Ma YG, et al. The DNA repair gene ERCC2/XPD polymorphism Arg 156Arg (A22541C) and risk of lung cancer in a Chinese population. Cancer Letters 2005; 223(2):219-226.
[115]Hu Z, Xu L, Shao M, et al. Polymorphisms in the two helicases ERCC2/XPD and ERCC3/XPB of the transcription factor ⅡH complex and risk of lung cancer:a case-control analysis in a Chinese population. Cancer Epidemiol Biomarkers Prev 2006; 15(7):1336-40.
[116]Liang Q Xing D, Miao X, et al. Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. Int J Cancer 2003; 105(5):669-73.
[117]Yin J, Vogel U, Ma Y, et al. Haplotypes of nine single nucleotide polymorphisms on chromosome 19q13.2-3 associated with susceptibility of lung cancer in a Chinese population. Mutat Res 2008; 641(1-2):12-8.
[118]Harms C SS, Sierra-Torres CH, Cajas-Salazar N, Au WW. Polymorphisms in DNA repair genes, chromosome aberrations, and lung cancer. Environ Mol Mutagen.2004;44(1):74-82.2004.
[119]Zhou W, Liu G, Miller DP, et al. Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer. Cancer Res 2002; 62(5):1377-81.
[120]Lopez-Cima MF, Gonzalez-Arriaga P, Garcia-Castro L, et al. Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer 2007; 7:162.
[121]Laine JP, Mocquet V, Bonfanti M, et al. Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription. DNA Repair 2007; 6(9):1264-1270.
[122]Matullo G, Palli D, Peluso M, et al. XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 2001; 22(9):1437-45.
[123]Hou S, Falt S, Yang K, et al. Differential interactions between GSTM1 and NAT2 genotypes on aromatic DNA adduct level and HPRT mutant frequency in lung cancer patients and population controls. Cancer Epidemiology Biomarkers& Prevention 2001; 10(2):133.
[124]Khan SG, Metter EJ, Tarone RE, et al. A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism. Carcinogenesis 2000; 21(10):1821-5.
[125]Khan SG, Muniz-Medina V, Shahlavi T, et al. The human XPC DNA repair gene:arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function. Nucleic Acids Res 2002; 30(16):3624-31.
[126]Vodicka P, Kumar R, Stetina R, et al. Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA. Carcinogenesis 2004; 25(5):757.
[127]Duell E, Wiencke J, Cheng T, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 2000; 21(5):965.
[128]Qiao Y, Spitz MR, Guo Z, et al. Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes. Mutat Res 2002; 509(1-2):165-74.
[129]Hemminki K, Xu G, Angelini S, et al. XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis 2001; 22(8):1185.
[130]Tang D, Cho S, Rundle A, et al. Polymorphisms in the DNA repair enzyme XPD are associated with increased levels of PAH-DNA adducts in a case-control study of breast cancer. Breast Cancer Res Treat 2002; 75(2):159-66.
[131]Lunn RM, Helzlsouer KJ, Parshad R, et al. XPD polymorphisms:effects on DNA repair proficiency. Carcinogenesis 2000; 21(4):551-5.
[132]Vogel U, Hedayati M, Dybdahl M, et al. Polymorphisms of the DNA repair gene XPD:correlations with risk of basal cell carcinoma revisited. Carcinogenesis 2001; 22(6):899-904.
[133]Topinka J, Hertz-Picciotto I, Dostal M, et al. The DNA repair gene XPD/ERCC2 polymorphisms Arg156Arg (exon 6) and Lys751Gln (exon 23) are closely associated. Toxicol Lett 2007; 172(1-2):85-9.
[134]King CR, Yu J, Freimuth RR, et al. Interethnic variability of ERCC2 polymorphisms. Pharmacogenomics J 2005; 5(1):54-9.
[135]Minelli C TJ, Abrams KR, Thakkinstian A, Attia J. The quality of meta-analyses of genetic association studies:a review with recommendations. Am J Epidemiol.2009 Dec 1;170(11):1333-43. Epub 2009 Nov 9.2009.
[136]Zhang D CC, Fu X, Gu S, Mao Y, Xie Y, Huang Y, Li Y. A meta-analysis of DNA repair gene XPC polymorphisms and cancer risk. J Hum Genet. 2008;53(1):18-33. Epub 2007 Nov 17.2007.
[137]Qiu L, Wang Z, Shi X. Associations between XPC polymorphisms and risk of cancers:A meta-analysis. Eur J Cancer 2008.ST; 44(15):2241-53.
[138]Wang F CD, Hu FL, Sui H, Han B, Li DD, Zhao YS. DNA repair gene XPD polymorphisms and cancer risk:a meta-analysis based on 56 case-control studies Cancer Epidemiol Biomarkers Prev.2008 Mar; 17(3):507-17.2008.
[139]Thakkinstian A, McElduff P, D'Este C, et al. A method for meta-analysis of molecular association studies. Statistics in medicine 2005; 24(9):1291-1306.
[1]Spitz MR WQ, Dong Q, Amos CI, Wu X. Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev.2003 Aug;12(8):689-98.2003.
[2]Wei QY, Spitz MR. The role of DNA repair capacity in susceptibility to lung cancer:A review. Cancer and Metastasis Reviews 1997; 16(3-4):295-307.
[3]Ronen A, Glickman B. Human DNA repair genes. Environmental and Molecular Mutagenesis 2001; 37(3):241.
[4]Tuteja N, Tuteja R. Unraveling DNA repair in human:molecular mechanisms and consequences of repair defect. Critical reviews in biochemistry and molecular biology 2001; 36(3):261.
[5]Peltomaki P. Deficient DNA mismatch repair:a common etiologic factor for colon cancer. Human Molecular Genetics 2001; 10(7):735.
[6]Hoeijmakers J. DNA Damage, Aging, and Cancer. New England Journal of Medicine 2009; 361(15):1475.
[7]Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 2002; 11(12):1513-30.
[8]Hoeijmakers J. Genome maintenance mechanisms for preventing cancer. Nature 2001; 411(6835):366-374.
[9]Khanna K, Jackson S. DNA double-strand breaks:signaling, repair and the cancer connection. Nature genetics 2001; 27(3):247-254.
[10]Wood RD MM, Lindahl T. Human DNA repair genes,2005. Mutat Res.2005 Sep 4;577(1-2):275-83.2005.
[11]Scagliotti G, Longo M, Novello S. Nonsmall cell lung cancer in never smokers. Current Opinion In Oncology 2009; 21(2):99.
[12]Braithwaite E, Wu,X. and Wang,Z.. Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts:involvement of two excision repair mechanisms in vitro. Carcinogenesis,19,1239-1246.1998.
[13]Wood R. Nucleotide excision repair in mammalian cells. Journal of Biological Chemistry 1997; 272(38):23465.
[14]Beernink P, Hwang M, Ramirez M, et al. Specificity of protein interactions mediated by BRCT domains of the XRCC1 DNA repair protein. Journal of Biological Chemistry 2005; 280(34):30206.
[15]Hung RJ, Hall J, Brennan P, et al. Genetic polymorphisms in the base excision repair pathway and cancer risk:a HuGE review. Am J Epidemiol 2005; 162(10):925-42.
[16]Caldecott K, Aoufouchi S, Johnson P, et al. XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase Ⅲ is a novel molecular'nick-sensor'in vitro. Nucleic Acids Research 1996; 24(22):4387.
[17]Masson M, Niedergang C, Schreiber V, et al. XRCC1 is specifically associated with poly (ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Molecular and Cellular Biology 1998; 18(6):3563.
[18]Whitehouse C, Taylor R, Thistlethwaite A, et al. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 2001; 104(1):107-117.
[19]Vidal AE, Boiteux, S., Hickson, I. D., and Radicella, J. P. XRCC1 coordinates the initial and late stages of DNA abasic site repair through proteinprotein interactions. EMBO J.,20:6530-6539,2001.2001.
[20]Thompson LH, West MG. XRCC1 keeps DNA from getting stranded. Mutat Res 2000;459(1):1-18.
[21]Levy N, Martz A, Bresson A, et al. XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage. Nucleic Acids Research 2006; 34(1):32.
[22]Fan J, Otterlei M, Wong H, et al. XRCC1 co-localizes and physically interacts with PCNA. Nucleic Acids Research 2004; 32(7):2193.
[23]Monaco R, Rosal R, Dolan MA, et al. Conformational effects of a common codon 399 polymorphism on the BRCT1 domain of the XRCC1 protein. Protein J2007;26(8):541-6.
[24]Li Y, Marion M, Rundle A, et al. A common polymorphism in XRCC1 as a biomarker of susceptibility for chemically induced genetic damage. Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals; 8(5):408.
[25]Matullo G, Palli D, Peluso M, et al. XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 2001; 22(9):1437-45.
[26]Lunn R, Langlois R, Hsieh L, et al. XRCC1 polymorphisms:effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Research 1999; 59(11):2557.
[27]Wang YF, Spitz MR, Zhu Y, et al. From genotype to phenotype:correlating XRCC1 polymorphisms with mutagen sensitivity. DNA Repair 2003; 2(8):901-908.
[28]Abdel-Rahman SZ, El-Zein RA. The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco-specific nitrosamine NNK. Cancer Lett 2000; 159(1):63-71.
[29]Duell E, Wiencke J, Cheng T, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 2000; 21(5):965.
[30]Gao WM, Romkes M, Siegfried JM, et al. Polymorphisms in DNA repair genes XPD and XRCC1 and p53 mutations in lung carcinomas of never-smokers. Mol Carcinog 2006; 45(11):828-32.
[31]Tuimala J, Szekely G, Gundy S, et al. Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes:role in mutagen sensitivity. Carcinogenesis 2002; 23(6):1003-1008.
[32]Vogel U, Nexo BA, Wallin H, et al. No association between base excision repair gene polymorphisms and risk of lung cancer. Biochem Genet 2004; 42(11-12):453-60.
[33]Zienolddiny S, Campa D, Lind H, et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis 2006; 27(3):560-7.
[34]Misra RR, Ratnasinghe D, Tangrea JA, et al. Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland. Cancer Lett 2003; 191(2):171-8.
[35]Shen M, Berndt SI, Rothman N, et al. Polymorphisms in the DNA base excision repair genes APEX1 and XRCC1 and lung cancer risk in Xuan Wei, China. Anticancer Res 2005; 25(1B):537-42.
[36]Lopez-Cima MF, Gonzalez-Arriaga P, Garcia-Castro L, et al. Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer 2007; 7:162.
[37]Jia-wei L, Li-na M, Guo-rong W. Relationship between polymorphisms of DNA repair gene XRCC1 and susceptibility, to lung cancer. China Oncology.15(2005)335-338 2005.
[38]Zhang X, Miao X, Liang G, et al. Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res 2005; 65(3):722-6.
[39]Hu Z, Ma H, Lu D, et al. A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking. Pharmacogenet Genomics 2005; 15(7):457-63.
[40]Hung RJ, Brennan P, Canzian F, et al. Large-scale investigation of base excision repair genetic polymorphisms and lung cancer risk in a multicenter study. J Natl Cancer Inst 2005; 97(8):567-76.
[41]David-Beabes GL, London SJ. Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians. Lung Cancer 2001; 34(3):333-9.
[42]Matullo G, Dunning AM, Guarrera S, et al. DNA repair polymorphisms and cancer risk in non-smokers in'a cohort study. Carcinogenesis 2006; 27(5):997-1007.
[43]Pachouri SS, Sobti RC, Kaur P, et al. Contrasting impact of DNA repair gene XRCC1 polymorphisms Arg399Gln and Arg194Trp on the risk of lung cancer in the north-Indian population. DNA Cell Biol 2007; 26(3):186-91.
[44]De Ruyck K, Szaumkessel M, De Rudder I, et al. Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk. Mutat Res 2007; 631(2):101-10.
[45]Ratnasinghe DL, Yao SX, Forman M, et al. Gene-environment interactions between the codon 194 polymorphism of XRCC1 and antioxidants influence lung cancer risk. Anticancer Res 2003; 23(1B):627-32.
[46]Kiyohara C, Takayama K, Nakanishi Y. Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk:a meta-analysis. Lung Cancer 2006; 54(3):267-83.
[47]Zheng H, Wang Z, Shi X. XRCC1 polymorphisms and lung cancer risk in Chinese populations:a meta-analysis. Lung cancer (Amsterdam, Netherlands) 2009:65(3):268.
[48]Wang Y YH, Li H, Li L, Wang H, Liu C, Zheng Y. Association between X-ray repair cross complementing group 1 codon 399 and 194 polymorphisms and lung cancer risk:a meta-analysis. Cancer Lett.2009 Nov 28;285(2):134-40. Epub 2009 May 28.2009.
[49]van Hoffen A, Balajee AS, van Zeeland AA, et al. Nucleotide excision repair and its interplay with transcription. Toxicology 2003; 193 (1-2):79-90.
[50]Sugasawa K. UV-induced ubiquitylation of XPC complex, the UV-DDB-ubiquitin ligase complex, and DNA repair. J Mol Histol 2006; 37(5-7):189-202.
[51]de Laat WL, Jaspers NG, Hoeijmakers JH. Molecular mechanism of nucleotide excision repair. Genes Dev 1999; 13(7):768-85.
[52]Melis JP, Wijnhoven SW, Beems RB, et al. Mouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes. Cancer Res 2008; 68(5):1347-53.
[53]L Li XL, CA Peterson and RJ Legerski. An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair. Mol. Cell. Biol.,101995,5396-5402, Vol 15, No.101995.
[54]Wu X, Fan W, Xu S, et al. Sensitization to the cytotoxicity of cisplatin by transfection with nucleotide excision repair gene xeroderma pigmentosun group A antisense RNA in human lung adenocarcinoma cells. Clin Cancer Res 2003; 9(16 Pt 1):5874-9.
[55]Butkiewicz D, Rusin M, Harris CC, et al. Identification of four single nucleotide polymorphisms in DNA repair genes:XPA and XPB (ERCC3) in Polish population. Hum Mutat 2000; 15(6):577-8.
[56]Kiyohara C, Yoshimasu K. Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk:a meta-analysis. Int J Med Sci 2007; 4(2):59-71.
[57]Akiri G, Nahari D, Finkelstein Y, et al. Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription. Oncogene 1998; 17(2):227-236.
[58]Miller KL, Karagas MR, Kraft P, et al. XPA, haplotypes, and risk of basal and squamous cell carcinoma. Carcinogenesis 2006; 27(8):1670-5.
[59]Wu X, Zhao H, Wei Q, et al. XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis 2003; 24(3):505-9.
[60]Park JY, Park SH, Choi JE, et al. Polymorphisms of the DNA repair gene xeroderma pigmentosum group A and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 2002; 11(10 Pt 1):993-7.
[61]Popanda O, Schattenberg T, Phong CT, et al. Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis 2004; 25(12):2433-41.
[62]Butkiewicz D, Popanda O, Risch A, et al. Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene. Cancer Epidemiol Biomarkers Prev 2004; 13(12):2242-6.
[63]Vogel U, Overvad K, Wallin H, et al. Combinations of polymorphisms in XPD, XPC and XPA in relation to risk of lung cancer. Cancer Lett 2005; 222(1):67-74.
[64]Qiao Y SM, Shen H, Guo Z, Shete S, Hedayati M, Grossman L, Mohrenweiser H, Wei Q. Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes. Carcinogenesis.2002 Feb;23(2):295-9.2002.
[65]Spitz MR, Wu X, Wang Y, et al. Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 2001; 61(4):1354-7.
[66]Raaschou-Nielsen O, Sorensen M, Overvad K, et al. Polymorphisms in nucleotide excision repair genes, smoking and intake of fruit and vegetables in relation to lung cancer.Lung Cancer 2008; 59(2):171-9.
[67]Janicijevic A SK, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst).2003 Mar 1;2(3):325-36.2003.
[68]Tapias A AJ, Forget D, Enzlin JH, Scharer OD, Coin F, Coulombe B, Egly JM. Ordered conformational changes in damaged DNA induced by nucleotide excision repair factors. J Biol Chem.2004 Apr 30;279(18):19074-83. Epub 2004 Feb 23.
[69]Masutani C, Araki M, Sugasawa K, et al. Identification and characterization of XPC-binding domain of hHR23B. Molecular and Cellular Biology 1997; 17(12):6915.
[70]Araki M, Masutani C, Takemura M, et al. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. The Journal of biological chemistry 2001; 276(22):18665.
[71]Sugasawa K, Shimizu Y, Iwai S, et al. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair 2002; 1(1):95.
[72]Costa R, Chigan as V, da Silva Galhardo R, et al. The eukaryotic nucleotide excision repair pathway. Biochimie 2003; 85(11):1083-1099.
[73]D'Errico M, Parlanti E, Teson M, et al. New functions of XPC in the protection of human skin cells from oxidative damage. EMBO J 2006; 25(18):4305-15.
[74]Hollander MC, Philburn RT, Patterson AD, et al. Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 2005; 102(37):13200-13205.
[75]Shen M, Berndt SI, Rothman N, et al. Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China. Int J Cancer 2005; 116(5):768-73.
[76]Bai Y, Xu L, Yang XB, et al. Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population:a case-control study. Bmc Cancer 2007; 7:-
[77]Chang JS, Wrensch MR, Hansen HM, et al. Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans. Int J Cancer 2008; 123(9):2095-104.
[78]Hu Z, Wang Y, Wang X, et al. DNA repair gene XPC genotypes/haplotypes and risk of lung cancer in a Chinese population. Int J Cancer 2005; 115(3):478-83.
[79]Lee GY, Jang JS, Lee SY, et al. XPC polymorphisms and lung cancer risk. Int J Cancer 2005; 115(5):807-13.
[80]Khan SG, Metter EJ, Tarone RE, et al. A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism. Carcinogenesis 2000; 21(10):1821-5.
[81]Khan SG, Muniz-Medina V, Shahlavi T, et al. The human XPC DNA repair gene: arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function. Nucleic Acids Res 2002; 30(16):3624-31.
[82]Vodicka P, Kumar R, Stetina R, et al. Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA. Carcinogenesis 2004; 25(5):757.
[83]Zhu Y YH, Chen Q, Lin J, Grossman HB, Dinney CP, Wu X, Gu J. Modulation of DNA damage/DNA repair capacity by XPC polymorphisms. DNA Repair (Amst).2008 Feb 1;7(2):141-8. Epub 2007 Oct 172008.
[84]Zhang D CC, Fu X, Gu S, Mao Y, Xie Y, Huang Y, Li Y. A meta-analysis of DNA repair gene XPC polymorphisms and cancer risk. J Hum Genet. 2008;53(1):18-33. Epub 2007 Nov 17.
[85]Francisco G, Menezes PR, Eluf-Neto J, et al. XPC polymorphisms play a role in tissue-specific carcinogenesis:a meta-analysis.Eur J Hum Genet 2008.ST.RE; 16(6):724-34.
[86]Qiu L, Wang Z, Shi X. Associations between XPC polymorphisms and risk of cancers:A meta-analysis. Eur J Cancer 2008.ST; 44(15):2241-53.
[87]Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 1998; 58(4):604-8.
[88]Coin F, Bergmann E, Tremeau-Bravard A, et al. Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH. The EMBO Journal 1999; 18(5):1357.
[89]Wolfe KJ, Wickliffe JK, Hill CE, et al. Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA expression. Pharmacogenet Genomics 2007; 17(11):897-905.
[90]Laine JP, Mocquet V, Bonfanti M, et al. Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription. DNA Repair 2007; 6(9):1264-1270.
[91]Qiao Y, Spitz MR, Guo Z, et al. Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes. Mutat Res 2002; 509(1-2):165-74.
[92]Hemminki K, Xu G, Angelini S, et al. XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis 2001; 22(8):1185.
[93]Tang D, Cho S, Rundle A, et al. Polymorphisms in the DNA repair enzyme XPD are associated with increased levels of PAH-DNA adducts in a case-control study of breast cancer. Breast Cancer Res Treat 2002; 75(2):159-66.
[94]Palli D, Russo A, Masala G, et al. DNA adduct levels and DNA repair polymorphisms in traffic-exposed workers and a general population sample. Int J Cancer 2001; 94(1):121-7.
[95]Hou S, Falt S, Angelini S, et al. The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis 2002; 23(4):599.
[96]Au WW, Salama SA, Sierra-Torres CH. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 2003; 111 (15):1843-50.
[97]Harms C SS, Sierra-Torres CH, Cajas-Salazar N, Au WW. Polymorphisms in DNA repair genes, chromosome aberrations, and lung cancer. Environ Mol Mutagen.2004;44(1):74-82.2004.
[98]Lunn RM, Helzlsouer KJ, Parshad R, et al. XPD polymorphisms:effects on DNA repair proficiency. Carcinogenesis 2000; 21(4):551-5.
[99]Zhou W, Liu G, Miller DP, et al. Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer. Cancer Res 2002; 62(5):1377-81.
[100]Xing D, Tan W, Wei Q, et al. Polymorphisms of the DNA repair gene XPD and risk of lung cancer in a Chinese population. Lung Cancer 2002; 38(2):123-9.
[101]Liang Q Xing D, Miao X, et al. Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. Int J Cancer 2003; 105(5):669-73.
[102]Yin J, Vogel U, Ma Y, et al. Polymorphism of the DNA repair gene ERCC2 Lys751 Gln and risk of lung cancer in a northeastern Chinese population. Cancer Genet Cytogenet 2006; 169(1):27-32.
[103]Butkiewicz D, Rusin M, Enewold L, et al. Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis 2001; 22(4):593-7.
[104]David-Beabes GL, Lunn RM, London SJ. No association between the XPD (Lys751Gln) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev 2001; 10(8):911-2.
[105]Park JY LS, Jeon HS, Park SH, Bae NC, Lee EB, Cha SI, Park JH, Kam S, Kim IS, Jung TH. Lys751Gln polymorphism in the DNA repair gene XPD and risk of primary lung cancer.. Lung Cancer.2002 Apr;36(1):15-6.2002.
[106]Chen S, Tang D, Xue K, et al. DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Carcinogenesis 2002;23(8):1321-5.
[107]Wang F, Chang D, Hu FL, et al. DNA repair gene XPD polymorphisms and cancer risk:a meta-analysis based on 56 case-control studies. Cancer Epidemiol Biomarkers Prev 2008; 17(3):507-17.
[2]Schwartz A, Ruckdeschel J. Familial lung cancer:genetic susceptibility and relationship to chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine 2006; 173(1):16.
[3]Hirvonen A, Husgafvel-Pursiainen K, Anttila S, et al. The GSTM1 null genotype as a potential risk modifier for squamous cell carcinoma of the lung. Carcinogenesis 1993; 14(7):1479.
[4]Wei Q, Cheng L, Hong W, et al. Reduced DNA repair capacity in lung cancer patients. Cancer Research 1996; 56(18):4103.
[5]Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 2002; 11(12):1513-30.
[6]Spitz MR WQ, Dong Q, Amos CI, Wu X. Genetic susceptibility to lung cancer:the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev.2003 Aug;12(8):689-98.2003.
[7]Wei QY, Spitz MR. The role of DNA repair capacity in susceptibility to lung cancer:A review. Cancer and Metastasis Reviews 1997; 16(3-4):295-307.
[8]Ronen A, Glickman B. Human DNA repair genes. Environmental and Molecular Mutagenesis 2001; 37(3):241.
[9]Hoeijmakers J. DNA Damage, Aging, and Cancer. New England Journal of Medicine 2009; 361(15):1475.
[10]Tuteja N, Tuteja R. Unraveling DNA repair in human:molecular mechanisms and consequences of repair defect. Critical reviews in biochemistry and molecular biology 2001; 36(3):261.
[11]Peltomaki P. Deficient DNA mismatch repair:a common etiologic factor for colon cancer. Human Molecular Genetics 2001; 10(7):735.
[12]Schwartz AG, Prysak GM, Bock CH, et al.-The molecular epidemiology of lung cancer. Carcinogenesis 2007; 28(3):507-518.
[13]Park JY, Lee SY, Jeon HS, et al. Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 2002;11(1):23-7.
[14]Hoeijmakers J. Genome maintenance mechanisms for preventing cancer. Nature 2001; 411(6835):366-374.
[15]Braithwaite E, Wu,X. and Wang,Z.. Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts:involvement of two excision repair mechanisms in vitro. Carcinogenesis,19,1239-1246. 1998.
[16]Beernink P, Hwang M, Ramirez M, et al. Specificity of protein interactions mediated by BRCT domains of the XRCC1 DNA repair protein. Journal of Biological Chemistry 2005; 280(34):30206.
[17]Caldecott K, Aoufouchi S, Johnson P, et al. XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular'nick-sensor'in vitro. Nucleic Acids Research 1996; 24(22):4387.
[18]Masson M, Niedergang C, Schreiber V, et al. XRCC1 is specifically associated with poly (ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Molecular and Cellular Biology 1998; 18(6):3563.
[19]Whitehouse C, Taylor R, Thistlethwaite A, et al. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 2001; 104(1):107-117.
[20]Vidal AE, Boiteux, S., Hickson, I. D., and Radicella, J. P. XRCC1 coordinates the initial and late stages of DNA abasic site repair through proteinprotein interactions. EMBO J.,20:6530-6539,2001.2001.
[21]Thompson LH, West MG XRCC1 keeps DNA from getting stranded. Mutat Res 2000; 459(1):1-18.
[22]van Hoffen A, Balajee AS, van Zeeland AA, et al. Nucleotide excision repair and its interplay with transcription. Toxicology 2003; 193(1-2):79-90.
[23]de Laat WL, Jaspers NG, Hoeijmakers JH. Molecular mechanism of nucleotide excision repair. Genes Dev 1999; 13(7):768-85.
[24]L Li XL, CA Peterson and RJ Legerski. An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair. Mol. Cell. Biol,101995,5396-5402, Vol 15, No.101995.
[25]Wu X, Fan W, Xu S, et al. Sensitization to the cytotoxicity of cisplatin by transfection with nucleotide excision repair gene xeroderma pigmentosun group A antisense RNA in human lung adenocarcinoma cells. Clin Cancer Res 2003; 9(16 Pt 1):5874-9.
[26]Masutani C, Araki M, Sugasawa K, et al. Identification and characterization of XPC-binding domain of hHR23B. Molecular and Cellular Biology 1997; 17(12):6915.
[27]Araki M, Masutani C, Takemura M, et al. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. The Journal of biological chemistry 2001; 276(22):18665.
[28]Sugasawa K, Shimizu Y, Iwai S, et al. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair 2002; 1(1):95.
[29]Costa R, Chigan as V, da Silva Galhardo R, et al. The eukaryotic nucleotide excision repair pathway. Biochimie 2003; 85(11):1083-1099.
[30]D'Errico M, Parlanti E, Teson M, et al. New functions of XPC in the protection of human skin cells from oxidative damage. EMBO J 2006; 25(18):4305-15.
[31]Hollander MC, Philburn RT, Patterson AD, et al. Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 2005; 102(37):13200-13205.
[32]Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 1998; 58(4):604-8.
[33]Coin F, Bergmann E, Tremeau-Bravard A, et al. Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH. The EMBO Journal 1999; 18(5):1357.
[34]Wood RD MM, Lindahl T. Human DNA repair genes,2005. Mutat Res.2005 Sep 4;577(1-2):275-83.2005.
[35]Scagliotti G, Longo M, Novello S. Nonsmall cell lung cancer in never smokers. Current Opinion In Oncology 2009; 21(2):99.
[36]Kiyohara C, Takayama K, Nakanishi Y. Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk:a meta-analysis. Lung Cancer 2006; 54(3):267-83.
[37]Michiels S, Danoy P, Dessen P, et al. Polymorphism discovery in 62 DNA repair genes and haplotype associations with risks for lung and head and neck cancers. Carcinogenesis 2007; 28(8):1731-9.
[38]McKusick LPaVA. Dissecting Human Disease in the Postgenomic Era. Science 16 February 2001:Vol.291. no.5507, pp.1224-1229 2001.
[39]Carlson CS EM, Rieder MJ, Smith JD, Kruglyak L, Nickerson DA. Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans. Nat Genet.2003 Apr;33(4):518-21. Epub 2003 Mar 24.2003.
[40]Tapp I, Malmberg L, Rennel E, et al. Homogeneous Scoring of Single-Nucleotide Polymorphisms:Comparison of the 5'-Nuclease TaqMan^(R) Assay and Molecular Beacon Probes. Biotechniques 2000; 28(4):732-739.
[41]Livak K, Flood S, Marmaro J, et al. Oligonucleotides with fluorescent dyes at opposite ends provide a quenched probe system useful for detecting PCR product and nucleic acid hybridization. Genome Research 1995; 4(6):357.
[42]Ding K ZK, He F, Shen Y. LDA--a java-based linkage disequilibrium analyzer. Bioinformatics.2003 Nov 1;19(16):2147-8.Click here to read 2003.
[43]Zhang W, Collins A, Maniatis N, et al. Properties of linkage disequilibrium (LD) maps. Proceedings of the National Academy of Sciences 2002; 99(26):17004.
[44]Johnson G, Esposito L, Barratt B, et al. Haplotype tagging for the identification of common disease genes. Nature genetics 2001; 29(2):233-237.
[45]Stephens M SM, Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001;68:978-89.2001.
[46]Hung RJ, Hall J, Brennan P, et al. Genetic polymorphisms in the base excision repair pathway and cancer risk:a HuGE review. Am J Epidemiol 2005; 162(10):925-42.
[47]Levy N, Martz A, Bresson A, et al. XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage. Nucleic Acids Research 2006; 34(1):32.
[48]Monaco R, Rosal R, Dolan MA, et al. Conformational effects of a common codon 399 polymorphism on the BRCT1 domain of the XRCC1 protein. Protein J 2007; 26(8):541-6.
[49]Shen M, Berndt SI, Rothman N, et al. Polymorphisms in the DNA base excision repair genes APEX1 and XRCC1 and lung cancer risk in Xuan Wei, China. Anticancer Res 2005; 25(1B):537-42.
[50]Matullo G, Dunning A, Guarrera S, et al. DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis 2006; 27(5):997.
[51]Pachouri SS, Sobti RC, Kaur P, et al. Contrasting impact of DNA repair gene XRCC1 polymorphisms Arg399Gln and Arg194Trp on the risk of lung cancer in the north-Indian population. DNA Cell Biol 2007; 26(3):186-91.
[52]Jia-wei L, Li-na M, Guo-rong W. Relationship between polymorphisms of DNA repair gene XRCC1 and susceptibility to lung cancer. China Oncology.15(2005)335-338 2005.
[53]De Ruyck K, Szaumkessel M, De Rudder I, et al. Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk. Mutat Res 2007; 631(2):101-10.
[54]David-Beabes GL, London SJ. Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians. Lung Cancer 2001; 34(3):333-9.
[55]Zhang X, Miao X, Liang G, et al. Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res 2005; 65(3):722-6.
[56]Fan J, Otterlei M, Wong H, et al. XRCC1 co-localizes and physically interacts with PCNA. Nucleic Acids Research 2004; 32(7):2193.
[57]Ratnasinghe DL, Yao SX, Forman M, et al. Gene-environment interactions between the codon 194 polymorphism of XRGC1 and antioxidants influence lung cancer risk. Anticancer Res 2003; 23(1B):627-32.
[58]Vogel U, Nexo BA, Wallin H, et al. No association between base excision repair gene polymorphisms and risk of lung cancer. Biochem Genet 2004; 42(11-12):453-60.
[59]Hu Z, Ma H, Lu D, et al. A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking. Pharmacogenet Genomics 2005; 15(7):457-63.
[60]Volker M MM, Karmakar P, van Hoffen A, Schul W, Vermeulen W, Hoeijmakers JH, van Driel R, van Zeeland AA, Mullenders LH. Sequential assembly of the nucleotide excision repair factors in vivo. Mol Cell.2001 Jul;8(1):213-24.2001.
[61]Guzder SN SC, Prakash L, Prakash S. (2006). Comp lex formation with damage recognition p rotein Rad14 is essential for Saccharomyces cerevisiae Radl Rad10 nuclease to perform its function in nucleotide excision repair in vivo. Mol Cell Biol,2006,26:1135-11412006.
[62]Stout GJ, Oosten M, Acherrat FZ, et al. Selective DNA damage responses in murine Xpa-/-, Xpc-/-and Csb-/-keratinocyte cultures. DNA Repair (Amst) 2005; 4(11):1337-44.
[63]Butkiewicz D, Rusin M, Harris CC, et al. Identification of four single nucleotide polymorphisms in DNA repair genes:XPA and XPB (ERCC3) in Polish population. Hum Mutat 2000; 15(6):577-8.
[64]Kiyohara C, Yoshimasu K. Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk:a meta-analysis. Int J Med Sci 2007; 4(2):59-71.
[65]Akiri Q Nahari D, Finkelstein Y, et al. Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription. Oncogene 1998; 17(2):227-236.
[66]Miller KL, Karagas MR, Kraft P, et al. XPA, haplotypes, and risk of basal and squamous cell carcinoma. Carcinogenesis 2006; 27(8):1670-5.
[67]Park JY, Park SH, Choi JE, et al. Polymorphisms of the DNA repair gene xeroderma pigmentosum group A and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 2002; 11(10 Pt 1):993-7.
[68]Wu X, Zhao H, Wei Q, et al. XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis 2003; 24(3):505-9.
[69]Popanda O, Schattenberg T, Phong CT, et al. Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis 2004; 25(12):2433-41.
[70]Butkiewicz D, Popanda O, Risch A, et al. Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene. Cancer Epidemiol Biomarkers Prev 2004; 13(12):2242-6.
[71]Vogel U, Overvad K, Wallin H, et al. Combinations of polymorphisms in XPD, XPC and XPA in relation to risk of lung cancer. Cancer Lett 2005; 222(1):67-74.
[72]Qiao Y SM, Shen H, Guo Z, Shete S, Hedayati M, Grossman L, Mohrenweiser H, Wei Q. Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes. Carcinogenesis.2002 Feb;23(2):295-9.2002.
[73]Spitz MR, Wu X, Wang Y, et al. Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 2001; 61(4):1354-7.
[74]Misra RR, Ratnasinghe D, Tangrea JA, et al. Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland. Cancer Lett 2003; 191(2):171-8.
[75]Zienolddiny S, Campa D, Lind H, et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis 2006; 27(3):560-7.
[76]Raaschou-Nielsen O, Sorensen M, Overvad K, et al. Polymorphisms in nucleotide excision repair genes, smoking and intake of fruit and vegetables in relation to lung cancer.Lung Cancer 2008; 59(2):171-9.
[77]Francisco G, Menezes PR, Eluf-Neto J, et al. XPC polymorphisms play a role in tissue-specific carcinogenesis:a meta-analysis.Eur J Hum Genet 2008.ST.RE; 16(6):724-34.
[78]Janicijevic A SK, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst).2003 Mar 1;2(3):325-36.2003.
[79]Tapias A AJ, Forget D, Enzlin JH, Scharer OD, Coin F, Coulombe B, Egly JM. Ordered conformational changes in damaged DNA induced by nucleotide excision repair factors. J Biol Chem.2004 Apr 30;279(18):19074-83. Epub 2004 Feb 23.
[80]Melis JP, Wijnhoven SW, Beems RB, et al. Mouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes. Cancer Res 2008; 68(5):1347-53.
[81]Zhu Y YH, Chen Q, Lin J, Grossman HB, Dinney CP, Wu X, Gu J. Modulation of DNA damage/DNA repair capacity by XPC polymorphisms. DNA Repair (Amst).2008 Feb 1;7(2):141-8. Epub 2007 Oct 17 2008.
[82]Hu Z, Wang Y, Wang X, et al. DNA repair gene XPC genotypes/haplotypes and risk of lung cancer in a Chinese population. Int J Cancer 2005; 115(3):478-83.
[83]Lee GY, Jang JS, Lee SY, et al. XPC polymorphisms and lung cancer risk. Int J Cancer 2005; 115(5):807-13.
[84]Shen M, Berndt SI, Rothman N, et al. Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China. Int J Cancer 2005; 116(5):768-73.
[85]Bai Y, Xu L, Yang XB, et al. Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population:a case-control study. Bmc Cancer 2007; 7:-.
[86]Chang JS, Wrensch MR, Hansen HM, et al. Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans. Int J Cancer 2008; 123(9):2095-104.
[87]Pagani F BF. Genomic variants in exons and introns:Identifying the splicing spoilers. Nat Rev Genet 2004;5:389-96.2004.
[88]Wolfe KJ, Wickliffe JK, Hill CE, et al. Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA expression. Pharmacogenet Genomics 2007; 17(11):897-905.
[89]Palli D, Russo A, Masala G, et al. DNA adduct levels and DNA repair polymorphisms in traffic-exposed workers and a general population sample. Int J Cancer 2001; 94(1):121-7.
[90]Au WW, Salama SA, Sierra-Torres CH. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 2003;111(15):1843-50.
[91]Hou S, Falt S, Angelini S, et al. The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis 2002; 23(4):599.
[92]Yin J, Vogel U, Ma Y, et al. Polymorphism of the DNA repair gene ERCC2 Lys751Gln and risk of lung cancer in a northeastern Chinese population. Cancer Genet Cytogenet 2006; 169(1):27-32.
[93]Butkiewicz D RM, Enewold L, Shields PG, Chorazy M, Harris CC. Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis. 2001 Apr;22(4):593-7.2001.
[94]David-Beabes GL, Lunn RM, London SJ. No association between the XPD (Lys751Gln) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev 2001; 10(8):911-2.
[95]Park JY LS, Jeon HS, Park SH, Bae NC, Lee EB, Cha SI, Park JH, Kam S, Kim IS, Jung TH. Lys751Gln polymorphism in the DNA repair gene XPD and risk of primary lung cancer.. Lung Cancer.2002 Apr;36(1):15-6.2002.
[96]Chen S, Tang D, Xue K, et al. DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Carcinogenesis 2002; 23(8):1321-5.
[97]Hahn LW RM, Moore JH. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics.2003 Feb 12;19(3):376-82.2003.
[98]Ritchie MD, Hahn LW, Roodi N, et al. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 2001; 69(1):138-47.
[99]胡永华；唐李陈.多因子降维法分析基因-基因交互作用的应用进展Recent advances in applications of multifactor dimensionality reduction for detecting gene-gene interactions.2007.
[100]Moore J, Gilbert J, Tsai C, et al. A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. Journal of theoretical biology 2006;241(2):252-261.
[101]Liu Z. Smoking and lung cancer in China:combined analysis of eight case-control studies. International Journal of Epidemiology 1992; 21(2):197.
[102]Wynder E, Hoffmann D. Smoking and lung cancer:scientific challenges and opportunities. Cancer Research 1994; 54(20):5284-5294.
[103]Paul I.W. De Bakker RRG, David Altshuler, Brian E. Henderson, and, Haiman CA. Transferability of Tag SNPs to Capture Common Genetic Variation in DNA Repair Genes Across Multiple Populations. Pacific Symposium on Biocomputing 11:478-486(2006) 2006.
[104]Duell EJ, Bracci PM, Moore JH, et al.*Detecting pathway-based gene-gene and gene-environment interactions in pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2008; 17(6):1470-9.
[105]Coffey C, Hebert P, Ritchie M, et al. An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction:The importance of model validation. BMC Bioinformatics 2004; 5:49.
[106]Marylyn D. Ritchie,2 Lance W. Hahn,1,2 Nady Roodi,3 L. Renee Bailey,1,2 William D. Dupont,4 Fritz F. Parl,3 and Jason H. Moore1. Multifactor-Dimensionality Reduction Reveals High-Order Interactions among Estrogen-Metabolism Genes in Sporadic Breast Cancer. Am J Hum Genet.2001 July; 69(1):138-147 2001.
[107]Lau J, Ioannidis J, Schmid C. Quantitative synthesis in systematic reviews. Annals of Internal Medicine 1997; 127(9):820.
[108]Chu S, Callaghan W, Kim S, et al. Maternal obesity and risk of gestational diabetes mellitus. Diabetes care 2007; 30(8):2070.
[109]Higgins J, Thompson S, Deeks J, et al. Measuring inconsistency in meta-analyses. British Medical Journal 2003; 327(7414):557.
[110]Warn D, Thompson S, Spiegelhalter D. Bayesian random effects meta-analysis of trials with binary outcomes:methods for the absolute risk difference and relative risk scales.
[111]Vogel U, Laros I, Jacobsen NR, et al. Two regions in chromosome 19ql3.2-3 are associated with risk of lung cancer. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 2004; 546(1-2):65-74.
[112]Xing DY, Qi J, Tan W, et al. Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing. Ch in J M ed Genet, February 2003, Vol.20, No.1 2003; 20(l):35-8.
[113]Xing D, Tan W, Wei Q, et al. Polymorphisms of the DNA repair gene XPD and risk of lung cancer in a Chinese population. Lung Cancer 2002; 38(2):123-9.
[114]Yin JY, Li JC, Ma YG, et al. The DNA repair gene ERCC2/XPD polymorphism Arg 156Arg (A22541C) and risk of lung cancer in a Chinese population. Cancer Letters 2005; 223(2):219-226.
[115]Hu Z, Xu L, Shao M, et al. Polymorphisms in the two helicases ERCC2/XPD and ERCC3/XPB of the transcription factor ⅡH complex and risk of lung cancer:a case-control analysis in a Chinese population. Cancer Epidemiol Biomarkers Prev 2006; 15(7):1336-40.
[116]Liang Q Xing D, Miao X, et al. Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. Int J Cancer 2003; 105(5):669-73.
[117]Yin J, Vogel U, Ma Y, et al. Haplotypes of nine single nucleotide polymorphisms on chromosome 19q13.2-3 associated with susceptibility of lung cancer in a Chinese population. Mutat Res 2008; 641(1-2):12-8.
[118]Harms C SS, Sierra-Torres CH, Cajas-Salazar N, Au WW. Polymorphisms in DNA repair genes, chromosome aberrations, and lung cancer. Environ Mol Mutagen.2004;44(1):74-82.2004.
[119]Zhou W, Liu G, Miller DP, et al. Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer. Cancer Res 2002; 62(5):1377-81.
[120]Lopez-Cima MF, Gonzalez-Arriaga P, Garcia-Castro L, et al. Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer 2007; 7:162.
[121]Laine JP, Mocquet V, Bonfanti M, et al. Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription. DNA Repair 2007; 6(9):1264-1270.
[122]Matullo G, Palli D, Peluso M, et al. XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 2001; 22(9):1437-45.
[123]Hou S, Falt S, Yang K, et al. Differential interactions between GSTM1 and NAT2 genotypes on aromatic DNA adduct level and HPRT mutant frequency in lung cancer patients and population controls. Cancer Epidemiology Biomarkers& Prevention 2001; 10(2):133.
[124]Khan SG, Metter EJ, Tarone RE, et al. A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism. Carcinogenesis 2000; 21(10):1821-5.
[125]Khan SG, Muniz-Medina V, Shahlavi T, et al. The human XPC DNA repair gene:arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function. Nucleic Acids Res 2002; 30(16):3624-31.
[126]Vodicka P, Kumar R, Stetina R, et al. Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA. Carcinogenesis 2004; 25(5):757.
[127]Duell E, Wiencke J, Cheng T, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 2000; 21(5):965.
[128]Qiao Y, Spitz MR, Guo Z, et al. Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes. Mutat Res 2002; 509(1-2):165-74.
[129]Hemminki K, Xu G, Angelini S, et al. XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis 2001; 22(8):1185.
[130]Tang D, Cho S, Rundle A, et al. Polymorphisms in the DNA repair enzyme XPD are associated with increased levels of PAH-DNA adducts in a case-control study of breast cancer. Breast Cancer Res Treat 2002; 75(2):159-66.
[131]Lunn RM, Helzlsouer KJ, Parshad R, et al. XPD polymorphisms:effects on DNA repair proficiency. Carcinogenesis 2000; 21(4):551-5.
[132]Vogel U, Hedayati M, Dybdahl M, et al. Polymorphisms of the DNA repair gene XPD:correlations with risk of basal cell carcinoma revisited. Carcinogenesis 2001; 22(6):899-904.
[133]Topinka J, Hertz-Picciotto I, Dostal M, et al. The DNA repair gene XPD/ERCC2 polymorphisms Arg156Arg (exon 6) and Lys751Gln (exon 23) are closely associated. Toxicol Lett 2007; 172(1-2):85-9.
[134]King CR, Yu J, Freimuth RR, et al. Interethnic variability of ERCC2 polymorphisms. Pharmacogenomics J 2005; 5(1):54-9.
[135]Minelli C TJ, Abrams KR, Thakkinstian A, Attia J. The quality of meta-analyses of genetic association studies:a review with recommendations. Am J Epidemiol.2009 Dec 1;170(11):1333-43. Epub 2009 Nov 9.2009.
[136]Zhang D CC, Fu X, Gu S, Mao Y, Xie Y, Huang Y, Li Y. A meta-analysis of DNA repair gene XPC polymorphisms and cancer risk. J Hum Genet. 2008;53(1):18-33. Epub 2007 Nov 17.2007.
[137]Qiu L, Wang Z, Shi X. Associations between XPC polymorphisms and risk of cancers:A meta-analysis. Eur J Cancer 2008.ST; 44(15):2241-53.
[138]Wang F CD, Hu FL, Sui H, Han B, Li DD, Zhao YS. DNA repair gene XPD polymorphisms and cancer risk:a meta-analysis based on 56 case-control studies Cancer Epidemiol Biomarkers Prev.2008 Mar; 17(3):507-17.2008.
[139]Thakkinstian A, McElduff P, D'Este C, et al. A method for meta-analysis of molecular association studies. Statistics in medicine 2005; 24(9):1291-1306.
[1]Spitz MR WQ, Dong Q, Amos CI, Wu X. Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev.2003 Aug;12(8):689-98.2003.
[2]Wei QY, Spitz MR. The role of DNA repair capacity in susceptibility to lung cancer:A review. Cancer and Metastasis Reviews 1997; 16(3-4):295-307.
[3]Ronen A, Glickman B. Human DNA repair genes. Environmental and Molecular Mutagenesis 2001; 37(3):241.
[4]Tuteja N, Tuteja R. Unraveling DNA repair in human:molecular mechanisms and consequences of repair defect. Critical reviews in biochemistry and molecular biology 2001; 36(3):261.
[5]Peltomaki P. Deficient DNA mismatch repair:a common etiologic factor for colon cancer. Human Molecular Genetics 2001; 10(7):735.
[6]Hoeijmakers J. DNA Damage, Aging, and Cancer. New England Journal of Medicine 2009; 361(15):1475.
[7]Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 2002; 11(12):1513-30.
[8]Hoeijmakers J. Genome maintenance mechanisms for preventing cancer. Nature 2001; 411(6835):366-374.
[9]Khanna K, Jackson S. DNA double-strand breaks:signaling, repair and the cancer connection. Nature genetics 2001; 27(3):247-254.
[10]Wood RD MM, Lindahl T. Human DNA repair genes,2005. Mutat Res.2005 Sep 4;577(1-2):275-83.2005.
[11]Scagliotti G, Longo M, Novello S. Nonsmall cell lung cancer in never smokers. Current Opinion In Oncology 2009; 21(2):99.
[12]Braithwaite E, Wu,X. and Wang,Z.. Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts:involvement of two excision repair mechanisms in vitro. Carcinogenesis,19,1239-1246.1998.
[13]Wood R. Nucleotide excision repair in mammalian cells. Journal of Biological Chemistry 1997; 272(38):23465.
[14]Beernink P, Hwang M, Ramirez M, et al. Specificity of protein interactions mediated by BRCT domains of the XRCC1 DNA repair protein. Journal of Biological Chemistry 2005; 280(34):30206.
[15]Hung RJ, Hall J, Brennan P, et al. Genetic polymorphisms in the base excision repair pathway and cancer risk:a HuGE review. Am J Epidemiol 2005; 162(10):925-42.
[16]Caldecott K, Aoufouchi S, Johnson P, et al. XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase Ⅲ is a novel molecular'nick-sensor'in vitro. Nucleic Acids Research 1996; 24(22):4387.
[17]Masson M, Niedergang C, Schreiber V, et al. XRCC1 is specifically associated with poly (ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Molecular and Cellular Biology 1998; 18(6):3563.
[18]Whitehouse C, Taylor R, Thistlethwaite A, et al. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 2001; 104(1):107-117.
[19]Vidal AE, Boiteux, S., Hickson, I. D., and Radicella, J. P. XRCC1 coordinates the initial and late stages of DNA abasic site repair through proteinprotein interactions. EMBO J.,20:6530-6539,2001.2001.
[20]Thompson LH, West MG. XRCC1 keeps DNA from getting stranded. Mutat Res 2000;459(1):1-18.
[21]Levy N, Martz A, Bresson A, et al. XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage. Nucleic Acids Research 2006; 34(1):32.
[22]Fan J, Otterlei M, Wong H, et al. XRCC1 co-localizes and physically interacts with PCNA. Nucleic Acids Research 2004; 32(7):2193.
[23]Monaco R, Rosal R, Dolan MA, et al. Conformational effects of a common codon 399 polymorphism on the BRCT1 domain of the XRCC1 protein. Protein J2007;26(8):541-6.
[24]Li Y, Marion M, Rundle A, et al. A common polymorphism in XRCC1 as a biomarker of susceptibility for chemically induced genetic damage. Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals; 8(5):408.
[25]Matullo G, Palli D, Peluso M, et al. XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 2001; 22(9):1437-45.
[26]Lunn R, Langlois R, Hsieh L, et al. XRCC1 polymorphisms:effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Research 1999; 59(11):2557.
[27]Wang YF, Spitz MR, Zhu Y, et al. From genotype to phenotype:correlating XRCC1 polymorphisms with mutagen sensitivity. DNA Repair 2003; 2(8):901-908.
[28]Abdel-Rahman SZ, El-Zein RA. The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco-specific nitrosamine NNK. Cancer Lett 2000; 159(1):63-71.
[29]Duell E, Wiencke J, Cheng T, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 2000; 21(5):965.
[30]Gao WM, Romkes M, Siegfried JM, et al. Polymorphisms in DNA repair genes XPD and XRCC1 and p53 mutations in lung carcinomas of never-smokers. Mol Carcinog 2006; 45(11):828-32.
[31]Tuimala J, Szekely G, Gundy S, et al. Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes:role in mutagen sensitivity. Carcinogenesis 2002; 23(6):1003-1008.
[32]Vogel U, Nexo BA, Wallin H, et al. No association between base excision repair gene polymorphisms and risk of lung cancer. Biochem Genet 2004; 42(11-12):453-60.
[33]Zienolddiny S, Campa D, Lind H, et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis 2006; 27(3):560-7.
[34]Misra RR, Ratnasinghe D, Tangrea JA, et al. Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland. Cancer Lett 2003; 191(2):171-8.
[35]Shen M, Berndt SI, Rothman N, et al. Polymorphisms in the DNA base excision repair genes APEX1 and XRCC1 and lung cancer risk in Xuan Wei, China. Anticancer Res 2005; 25(1B):537-42.
[36]Lopez-Cima MF, Gonzalez-Arriaga P, Garcia-Castro L, et al. Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer 2007; 7:162.
[37]Jia-wei L, Li-na M, Guo-rong W. Relationship between polymorphisms of DNA repair gene XRCC1 and susceptibility, to lung cancer. China Oncology.15(2005)335-338 2005.
[38]Zhang X, Miao X, Liang G, et al. Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res 2005; 65(3):722-6.
[39]Hu Z, Ma H, Lu D, et al. A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking. Pharmacogenet Genomics 2005; 15(7):457-63.
[40]Hung RJ, Brennan P, Canzian F, et al. Large-scale investigation of base excision repair genetic polymorphisms and lung cancer risk in a multicenter study. J Natl Cancer Inst 2005; 97(8):567-76.
[41]David-Beabes GL, London SJ. Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians. Lung Cancer 2001; 34(3):333-9.
[42]Matullo G, Dunning AM, Guarrera S, et al. DNA repair polymorphisms and cancer risk in non-smokers in'a cohort study. Carcinogenesis 2006; 27(5):997-1007.
[43]Pachouri SS, Sobti RC, Kaur P, et al. Contrasting impact of DNA repair gene XRCC1 polymorphisms Arg399Gln and Arg194Trp on the risk of lung cancer in the north-Indian population. DNA Cell Biol 2007; 26(3):186-91.
[44]De Ruyck K, Szaumkessel M, De Rudder I, et al. Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk. Mutat Res 2007; 631(2):101-10.
[45]Ratnasinghe DL, Yao SX, Forman M, et al. Gene-environment interactions between the codon 194 polymorphism of XRCC1 and antioxidants influence lung cancer risk. Anticancer Res 2003; 23(1B):627-32.
[46]Kiyohara C, Takayama K, Nakanishi Y. Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk:a meta-analysis. Lung Cancer 2006; 54(3):267-83.
[47]Zheng H, Wang Z, Shi X. XRCC1 polymorphisms and lung cancer risk in Chinese populations:a meta-analysis. Lung cancer (Amsterdam, Netherlands) 2009:65(3):268.
[48]Wang Y YH, Li H, Li L, Wang H, Liu C, Zheng Y. Association between X-ray repair cross complementing group 1 codon 399 and 194 polymorphisms and lung cancer risk:a meta-analysis. Cancer Lett.2009 Nov 28;285(2):134-40. Epub 2009 May 28.2009.
[49]van Hoffen A, Balajee AS, van Zeeland AA, et al. Nucleotide excision repair and its interplay with transcription. Toxicology 2003; 193 (1-2):79-90.
[50]Sugasawa K. UV-induced ubiquitylation of XPC complex, the UV-DDB-ubiquitin ligase complex, and DNA repair. J Mol Histol 2006; 37(5-7):189-202.
[51]de Laat WL, Jaspers NG, Hoeijmakers JH. Molecular mechanism of nucleotide excision repair. Genes Dev 1999; 13(7):768-85.
[52]Melis JP, Wijnhoven SW, Beems RB, et al. Mouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes. Cancer Res 2008; 68(5):1347-53.
[53]L Li XL, CA Peterson and RJ Legerski. An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair. Mol. Cell. Biol.,101995,5396-5402, Vol 15, No.101995.
[54]Wu X, Fan W, Xu S, et al. Sensitization to the cytotoxicity of cisplatin by transfection with nucleotide excision repair gene xeroderma pigmentosun group A antisense RNA in human lung adenocarcinoma cells. Clin Cancer Res 2003; 9(16 Pt 1):5874-9.
[55]Butkiewicz D, Rusin M, Harris CC, et al. Identification of four single nucleotide polymorphisms in DNA repair genes:XPA and XPB (ERCC3) in Polish population. Hum Mutat 2000; 15(6):577-8.
[56]Kiyohara C, Yoshimasu K. Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk:a meta-analysis. Int J Med Sci 2007; 4(2):59-71.
[57]Akiri G, Nahari D, Finkelstein Y, et al. Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription. Oncogene 1998; 17(2):227-236.
[58]Miller KL, Karagas MR, Kraft P, et al. XPA, haplotypes, and risk of basal and squamous cell carcinoma. Carcinogenesis 2006; 27(8):1670-5.
[59]Wu X, Zhao H, Wei Q, et al. XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis 2003; 24(3):505-9.
[60]Park JY, Park SH, Choi JE, et al. Polymorphisms of the DNA repair gene xeroderma pigmentosum group A and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 2002; 11(10 Pt 1):993-7.
[61]Popanda O, Schattenberg T, Phong CT, et al. Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis 2004; 25(12):2433-41.
[62]Butkiewicz D, Popanda O, Risch A, et al. Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene. Cancer Epidemiol Biomarkers Prev 2004; 13(12):2242-6.
[63]Vogel U, Overvad K, Wallin H, et al. Combinations of polymorphisms in XPD, XPC and XPA in relation to risk of lung cancer. Cancer Lett 2005; 222(1):67-74.
[64]Qiao Y SM, Shen H, Guo Z, Shete S, Hedayati M, Grossman L, Mohrenweiser H, Wei Q. Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes. Carcinogenesis.2002 Feb;23(2):295-9.2002.
[65]Spitz MR, Wu X, Wang Y, et al. Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 2001; 61(4):1354-7.
[66]Raaschou-Nielsen O, Sorensen M, Overvad K, et al. Polymorphisms in nucleotide excision repair genes, smoking and intake of fruit and vegetables in relation to lung cancer.Lung Cancer 2008; 59(2):171-9.
[67]Janicijevic A SK, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst).2003 Mar 1;2(3):325-36.2003.
[68]Tapias A AJ, Forget D, Enzlin JH, Scharer OD, Coin F, Coulombe B, Egly JM. Ordered conformational changes in damaged DNA induced by nucleotide excision repair factors. J Biol Chem.2004 Apr 30;279(18):19074-83. Epub 2004 Feb 23.
[69]Masutani C, Araki M, Sugasawa K, et al. Identification and characterization of XPC-binding domain of hHR23B. Molecular and Cellular Biology 1997; 17(12):6915.
[70]Araki M, Masutani C, Takemura M, et al. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. The Journal of biological chemistry 2001; 276(22):18665.
[71]Sugasawa K, Shimizu Y, Iwai S, et al. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair 2002; 1(1):95.
[72]Costa R, Chigan as V, da Silva Galhardo R, et al. The eukaryotic nucleotide excision repair pathway. Biochimie 2003; 85(11):1083-1099.
[73]D'Errico M, Parlanti E, Teson M, et al. New functions of XPC in the protection of human skin cells from oxidative damage. EMBO J 2006; 25(18):4305-15.
[74]Hollander MC, Philburn RT, Patterson AD, et al. Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 2005; 102(37):13200-13205.
[75]Shen M, Berndt SI, Rothman N, et al. Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China. Int J Cancer 2005; 116(5):768-73.
[76]Bai Y, Xu L, Yang XB, et al. Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population:a case-control study. Bmc Cancer 2007; 7:-
[77]Chang JS, Wrensch MR, Hansen HM, et al. Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans. Int J Cancer 2008; 123(9):2095-104.
[78]Hu Z, Wang Y, Wang X, et al. DNA repair gene XPC genotypes/haplotypes and risk of lung cancer in a Chinese population. Int J Cancer 2005; 115(3):478-83.
[79]Lee GY, Jang JS, Lee SY, et al. XPC polymorphisms and lung cancer risk. Int J Cancer 2005; 115(5):807-13.
[80]Khan SG, Metter EJ, Tarone RE, et al. A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism. Carcinogenesis 2000; 21(10):1821-5.
[81]Khan SG, Muniz-Medina V, Shahlavi T, et al. The human XPC DNA repair gene: arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function. Nucleic Acids Res 2002; 30(16):3624-31.
[82]Vodicka P, Kumar R, Stetina R, et al. Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA. Carcinogenesis 2004; 25(5):757.
[83]Zhu Y YH, Chen Q, Lin J, Grossman HB, Dinney CP, Wu X, Gu J. Modulation of DNA damage/DNA repair capacity by XPC polymorphisms. DNA Repair (Amst).2008 Feb 1;7(2):141-8. Epub 2007 Oct 172008.
[84]Zhang D CC, Fu X, Gu S, Mao Y, Xie Y, Huang Y, Li Y. A meta-analysis of DNA repair gene XPC polymorphisms and cancer risk. J Hum Genet. 2008;53(1):18-33. Epub 2007 Nov 17.
[85]Francisco G, Menezes PR, Eluf-Neto J, et al. XPC polymorphisms play a role in tissue-specific carcinogenesis:a meta-analysis.Eur J Hum Genet 2008.ST.RE; 16(6):724-34.
[86]Qiu L, Wang Z, Shi X. Associations between XPC polymorphisms and risk of cancers:A meta-analysis. Eur J Cancer 2008.ST; 44(15):2241-53.
[87]Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 1998; 58(4):604-8.
[88]Coin F, Bergmann E, Tremeau-Bravard A, et al. Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH. The EMBO Journal 1999; 18(5):1357.
[89]Wolfe KJ, Wickliffe JK, Hill CE, et al. Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA expression. Pharmacogenet Genomics 2007; 17(11):897-905.
[90]Laine JP, Mocquet V, Bonfanti M, et al. Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription. DNA Repair 2007; 6(9):1264-1270.
[91]Qiao Y, Spitz MR, Guo Z, et al. Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes. Mutat Res 2002; 509(1-2):165-74.
[92]Hemminki K, Xu G, Angelini S, et al. XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis 2001; 22(8):1185.
[93]Tang D, Cho S, Rundle A, et al. Polymorphisms in the DNA repair enzyme XPD are associated with increased levels of PAH-DNA adducts in a case-control study of breast cancer. Breast Cancer Res Treat 2002; 75(2):159-66.
[94]Palli D, Russo A, Masala G, et al. DNA adduct levels and DNA repair polymorphisms in traffic-exposed workers and a general population sample. Int J Cancer 2001; 94(1):121-7.
[95]Hou S, Falt S, Angelini S, et al. The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis 2002; 23(4):599.
[96]Au WW, Salama SA, Sierra-Torres CH. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 2003; 111 (15):1843-50.
[97]Harms C SS, Sierra-Torres CH, Cajas-Salazar N, Au WW. Polymorphisms in DNA repair genes, chromosome aberrations, and lung cancer. Environ Mol Mutagen.2004;44(1):74-82.2004.
[98]Lunn RM, Helzlsouer KJ, Parshad R, et al. XPD polymorphisms:effects on DNA repair proficiency. Carcinogenesis 2000; 21(4):551-5.
[99]Zhou W, Liu G, Miller DP, et al. Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer. Cancer Res 2002; 62(5):1377-81.
[100]Xing D, Tan W, Wei Q, et al. Polymorphisms of the DNA repair gene XPD and risk of lung cancer in a Chinese population. Lung Cancer 2002; 38(2):123-9.
[101]Liang Q Xing D, Miao X, et al. Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. Int J Cancer 2003; 105(5):669-73.
[102]Yin J, Vogel U, Ma Y, et al. Polymorphism of the DNA repair gene ERCC2 Lys751 Gln and risk of lung cancer in a northeastern Chinese population. Cancer Genet Cytogenet 2006; 169(1):27-32.
[103]Butkiewicz D, Rusin M, Enewold L, et al. Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis 2001; 22(4):593-7.
[104]David-Beabes GL, Lunn RM, London SJ. No association between the XPD (Lys751Gln) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev 2001; 10(8):911-2.
[105]Park JY LS, Jeon HS, Park SH, Bae NC, Lee EB, Cha SI, Park JH, Kam S, Kim IS, Jung TH. Lys751Gln polymorphism in the DNA repair gene XPD and risk of primary lung cancer.. Lung Cancer.2002 Apr;36(1):15-6.2002.
[106]Chen S, Tang D, Xue K, et al. DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Carcinogenesis 2002;23(8):1321-5.
[107]Wang F, Chang D, Hu FL, et al. DNA repair gene XPD polymorphisms and cancer risk:a meta-analysis based on 56 case-control studies. Cancer Epidemiol Biomarkers Prev 2008; 17(3):507-17.
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