XPC基因Ala499Val、Lys939Gln多态与食管癌、贲门癌发病风险的关联

背景与目的：XPC基因参与核苷酸切除修复,该基因存在单核苷酸多态性（SNP）位点,并可能通过SNP位点碱基的改变影响其修复能力及疾病易感性。本研究旨在探讨XPC基因第8外显子Ala499Val及第15外显子Lys939G1nSNP与河北省食管癌、贲门癌高发区-磁县和涉县人群食管鳞状细胞癌（esophageal sguamous cell carcinoma,ESCC）和贲门腺癌（gastric cardiac adenocorcinoma,GCA）遗传易感性的关系。方法：采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）分析方法检测327例ESCC患者、253例GCA患者和612名健康对照的XPC基因第8外显子Ala499Val及第15外显子Lys939Gln SNP的基因型。结果：ESCC患者组、GCA患者组上消化道肿瘤家族史阳性个体比例明显高于对照组,上消化道肘t瘤家族史可增加ESCC、GCA的发病风险（经性别和年龄校正后的OR=1．76和1．77．95％CI=1．34～2．32和1．31～2．39）.ESCC患者组和对照组的XPC基因第8外显子C、T等位基因频率及C／C、C／T、T／T基因型分布差异均无显著性（P〉0．05）。GCA患者组T等位基因频率（26．5％）显著低于对照组（32．5％）,两组相比差异有显著性（x^2=6．12,P=0．01）;与C／C基因型相比,携带C／T基因型可显著降低GCA的发病风险（OR=0．62,95％CI=0．45～0．84）。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与C／C基因型相比,携带C／T基因型可显著降低吸烟个体和家族史阴性个体GCA的发病风险（OR均等于0．57,95％CI=0．36～0．91和0．37～0．88）。在ESCC、GCA患者组和对照组之间,XPC第15外显子A、C等位基因频率及A／A、A／C、C／C基因型分布差异均无显著性（P〉0．05）。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与A／A基因型相比,携带C／C基因型可显著增加非吸烟个体ESCC的发病风险（OR=2．05,95％CI=1．15～3．66）。单体型分析显示,A／T、A／C、C／T、C／C四种单体型,在ESCC患者组与对照组之间分布差异无显著性（P〉0．05）;在GCA患者组与对照组之间分布差异有显著性（P=0．02）。与A／T单体型相比,携带A／C、C／C单体型可显著增加GCA的发病风险（OR=1．35和1．46,95％CI=1．01～1．81和1．06～2．00）。结论：在河北省食管癌、贲门癌高发区一磁县和涉县人群中,携带XPC基因第8外显子C／T基因型可能明显降低GCA的发病风险;第15外显子Lys939Gln SNP可能与ESCC、GCA的发病风险无关,但分层分析发现携带第15外显子C／C基因型可能增加非吸烟个体ESCC的发病风险;携带A／C、C／C单体型可能增加GCA的发病风险。     

XPC 基因多态性与食管鳞状细胞癌、贲门腺癌的发病风险

 目的 探讨DNA修复基因XPC第9内含子PAT＋／-和第15外显子A2920C单核苷酸多态性（SNP）与河北省食管癌、贲门癌高发区磁县和涉县人群食管鳞状细胞癌（ESCC）和贲门腺癌（GCA）遗传易感性的关系。方法 采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法检测327名ESCC患者、253名GCA患者和612名健康对照个体的XPC基因第9内含子PAT＋／-及第15外显子A2920C SNP的基因型，比较各组间等位基因及基因型频率的分布。结果 XPC基因第9内含子PAT＋／-和第15外显子A2920C的基因型及等位基因型频率在ESCC患者组、GCA患者组和对照组之间，其总体分布均无显著性差异（P〉0．05）。根据吸烟状况和上消化道肿瘤家族史分层分析发现，与A／A基因型比较，携带C／C基因型可能增加非吸烟个体ESCC的发病风险（经性别、年龄和上消化道肿瘤家族史校正后的OR=2．09，95％CI=1．14～3．81）。结论 XPC基因第15外显子C／C基因型可能是影响河北省食管癌、贲门癌高发区磁县和涉县非吸烟人群ESCC发病风险的因素之一。     

XPC基因Ala499Val、Lys939Gln多态与食管癌、贲门癌发病风险的关联

背景与目的:XPC基因参与核苷酸切除修复,该基因存在单核苷酸多态性(SNP)位点,并可能通过SNP位点碱基的改变影响其修复能力及疾病易感性。本研究旨在探讨XPC基因第8外显子Ala499Val及第15外显子Lys939GlnSNP与河北省食管癌、贲门癌高发区—磁县和涉县人群食管鳞状细胞癌(esophagealsguamouscellcarcinoma,ESCC)和贲门腺癌(gastriccardiacadenocorcinoma,GCA)遗传易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法检测327例ESCC患者、253例GCA患者和612名健康对照的XPC基因第8外显子Ala499Val及第15外显子Lys939GlnSNP的基因型。结果:ESCC患者组、GCA患者组上消化道肿瘤家族史阳性个体比例明显高于对照组,上消化道肿瘤家族史可增加ESCC、GCA的发病风险(经性别和年龄校正后的OR=1.76和1.77,95%CI=1.34～2.32和1.31～2.39)。ESCC患者组和对照组的XPC基因第8外显子C、T等位基因频率及C/C、C/T、T/T基因型分布差异均无显著性(P>0.05)。GCA患者组T等位基因频率(26.5%)显著低于对照组(32.5%),两组相比差异有显著性(χ2=6.12,P=0.01);与C/C基因型相比,携带C/T基因型可显著降低GCA的发病风险(OR=0.62,95%CI=0.45～0.84)。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与C/C基因型相比,携带C/T基因型可显著降低吸烟个体和家族史阴性个体GCA的发病风险(OR均等于0.57,95%CI=0.36～0.91和0.37～0.88)。在ESCC、GCA患者组和对照组之间,XPC第15外显子A、C等位基因频率及A/A、A/C、C/C基因型分布差异均无显著性(P>0.05)。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与A/A基因型相比,携带C/C基因型可显著增加非吸烟个体ESCC的发病风险(OR=2.05,95%CI=1.15～3.66)。单体型分析显示,A/T、A/C、C/T、C/C四种单体型,在ESCC患者组与对照组之间分布差异无显著性(P>0.05);在GCA患者组与对照组之间分布差异有显著性(P=0.02)。与A/T单体型相比,携带A/C、C/C单体型可显著增加GCA的发病风险(OR=1.35和1.46,95%CI=1.01～1.81和1.06～2.00)。结论:在河北省食管癌、贲门癌高发区—磁县和涉县人群中,携带XPC基因第8外显子C/T基因型可能明显降低GCA的发病风险;第15外显子Lys939GlnSNP可能与ESCC、GCA的发病风险无关,但分层分析发现携带第15外显子C/C基因型可能增加非吸烟个体ESCC的发病风险;携带A/C、C/C单体型可能增加GCA的发病风险。     

DNA修复基因XPD 312 Asn和751Lys多态性与非吸烟女性肺癌的关系

目的 着色性干皮病互补基因D(xeroderma pigmentosum group D,XPD)是一种重要的DNA损伤修复基因,其常见的多态是位于751密码子的A→C颠换和312密码子G→A转换。本研究旨在探讨XPD基因751位点和312位点单核苷酸多态性与非吸烟女性肺癌易感性的关系。方法 采用病例-对照研究方法,纳入非吸烟女性肺癌患者222人和对照222人。以聚合酶链反应-限制性片段长度多态性方法分析XPD基因Lys751Gln和Asp312Asn多态基因型。结果 携带至少1个751Gln等位基因者和携带至少1个312Asn等位基因者患肺癌的风险均显著增高,调整OR分别为3.36(95%CI为2.29-4.90)和1.83(95%CI为1.16-2.91)。结论 XPD基因Lys751Gln和Asp312Asn多态是非吸烟女性肺癌的遗传易感因素。     

东北地区汉族人群XPD单核苷酸多态性与结肠癌易感相关性的研究

目的:研究核苷酸切除修复基因XPD单核苷酸多态性与东北地区汉族人群结肠癌风险的关系.方法:以聚合酶链反应-限制性片段长度多态性方法分析170例结肠癌患者标本XPD基因Asp312Asn和Lys751Gln多态性.比较不同基因型与结肠癌风险的关系.结果:Lys751Gln多态在结肠癌患者中的分布和正常对照组差异无统计学意义,与结肠癌风险无关.结肠癌患者中Asp/Asn和Asn/Asn基因型频率明显高于正常对照组,P=0.016;与携带312 Asp/Asp基因型者比较,携带至少1个312 Asn等位基因者(即Asp/Asn和Asn/Asn基因型)罹患结肠癌的风险增加2.11倍(95%CI:1.21～3.66).结论:XPD基因Asp312Asn多态是东北地区汉族人群结肠癌遗传易感因素.     

DNA修复基因XPD单核苷酸多态与胆道癌遗传易感性

目的:研究核苷酸切除修复基因XPDAsp312Asn位点以及Lys751Gln位点多态与上海市区人群胆道癌风险的关系。方法:采用全人群病例-对照研究的方法运用PCR-RFLP对443名胆道癌患者和448名正常对照进行基因型分析。比较各基因型在病例与对照中分布频率的差异,并探讨基因、环境因素在胆道癌发生过程中的作用。结果:与携带XPD 751Lys/Lys基因型者比较,携带Gln/Gln基因型者罹患胆道癌的风险显著增加(校正OR=6.32;95%CI=1.16~34.53)。按解剖部位分析显示,风险增高只限于壶腹部癌(校正的OR=13.17;95%CI=1.71~101.38)。携带312Asn/Asn基因型者罹患壶腹部癌的风险显著高于携带Asp/Asp基因型者(校正后OR=20.09;95%CI=1.13~357.99)。在不伴有胆石症人群中,751Gln/Gln基因型携带者罹患胆道癌风险增加(校正后OR=5.92;95%CI=1.05~33.36),提示在不伴有胆石症人群中,遗传因素可能是发生胆道癌的影响因素。而在饮酒人群中携带751Lys/Gln或Gln/Gln基因型者较携带Lys/Lys基因型者患胆道癌风险增加约3倍。结论:XPD 312Asn等位基因以及751Gln等位基因可能是中国上海地区人群胆道癌尤其是壶腹部癌风险的遗传易感因素。     

XRCC5基因多态性与高发区食管癌、贲门癌遗传易感性的相关性

背景与目的:XRCC5为DNA双链断裂修复基因,其表达异常、活性紊乱与肿瘤的发生和发展密切相关.本研究旨在探讨XRCC5基因多态性与河北省食管癌高发区一磁、涉县人群食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)和贲门腺癌(gastric cardiac adenocarcinoma,GCA)遗传易感性的关系.方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测329例ESCC患者、255名GCA患者和631例健康对照人群XRCC5 C74468A、G74582A单核苷酸多态性(single nucleotide polymorphisms,SNP)的基因型分布.结果:XRCC5基因C74468A C和A的等位基因频率及C/C、A/C、A/A基因型频率在ESCC、GCA及对照组之间差异无显著性(P＞0.05).根据吸烟状况和上消化道肿瘤(UGIC)家族史分层分析发现,携带A等位基因(A/C A/A基因型)可能降低上消化道肿瘤阳性家族史人群的ESCC、GCA发病风险(经性别、年龄和吸烟校正后的OR分别为0.58和0.61,95%CI分别为0.38～0.90和0.38～0.97).XRCC5 G74582A基因G、A等位基因频率及鞍A/A、A/G、G/G基因型频率在ESCC、GCA及对照组之间亦差异无显著性(P＞0.05).分层分析发现,携带G等位基因(A/G G/G基因型)可能降低上消化道肿瘤阳性家族史人群的GCA发病风险(经性别、年龄和吸烟校正后的OR为0.63,95%CI为0.40～0.98).两多态性位点联合分析显示,ESCC、GCA患者与健康对照组的单体型分布差异也无显著性(P＞0.05).结论:XRCC5 C74468A A等位基因(A/C A/A基因型)可能降低磁县和涉县上消化道肿瘤阳性家族史人群的ESCC、GCA发病风险.而G74582A G等位基因(A/G G/G基因型)可能仅降低该地区上消化道肿瘤阳性家族史人群的GCA发病风险.     

XPD Lys751Gln多态性与成年人急性白血病发病风险的关系研究

 目的　探讨核苷酸切除修复基因XPD Lys751Gln多态性与成年人急性白血病（AL）发病风险的关系。方法　按照1∶1配对病例对照研究方法,选择100例成年人AL患者为病例组,100名健康体检人群为对照组,采用聚合酶链反应-限制性片段长度多态性方法检测观察对象外周血XPD Lys751Gln基因多态性。结果　成年人AL病例组和对照组Lys／Lys、Lys／Gln、Gln／Gln基因型分布频率分别为83 %、16 %、1 %和90 %、10 %、0,两组比较差异无统计学意义（χ2＝1.44,P＝0.49）;携带XPD Lys751Gln突变基因（Lys／Gln+Gln／Gln）的个体不增加AL的发病风险（χ2＝2.10,P＝0.15,OR＝1.84;95 % CI 0.80～4.25）。按FAB形态学分型,携带XPD Lys751Gln突变基因型（Lys／Gln+ Gln／Gln）个体患AL的危险度增加（OR＝2.77,95 % CI 0.99～7.73）。结论　XPD Lys751Gln可能与成年人急性淋巴细胞白血病的发病风险有关。     

XPA基因多态性与食管癌、贲门癌发病风险的关联

目的 探讨XPA基因5’-非编码区转录启始密码子ATG上游第4位A23G和228密码子G709A单核苷酸多态性（Single nucleotide polymorphism,SNP）与河北省食管癌、贲门癌高发区-磁县和涉县人群食管鳞状细胞癌（Esophageal squamous cell carcinoma,ESCC）和贲门腺癌（Gastric cardiac adenocarcinoma,GCA）遗传易感性的关系。方法 采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法检测327名ESCC患者、253名GCA患者和612名健康对照的XPA A23G和G709A SNP的基因型。结果 XPA基因A23G的等位基因和基因型频率在ESCC和健康对照之间,总体分布有显著性差异。与A／A基因型相比,A／G＋G／G基因型可显著降低ESCC的发病风险。分层分析显示,此保护作用在非吸烟组和吸烟组人群中尤为明显。此保护作用在UGIC家族史阴性人群中也很明显。在GCA和健康对照之间,A23G等位基因频率和基因型频率总体分布无显著性差异（P〉0．05）。与A／A基因型相比,A／G＋G／G基因型可显著降低GCA的发病风险。分层分析显示,在非吸烟组中,GCA患者组和健康对照之间,基因型频率分布有显著性差异（P〈0．05）。与A／A基因型相比,A／G＋G／G基因型可显著降低非吸烟人群GCA的发病风险。结论 XPA基因A23G含突变等位基因（G）的基因型（A／G＋G／G）可能是影响河北省食管癌、贲门癌的高发区——磁县和涉县人群ESCC发病风险的因素之一.     

DNA修复基因XPD751基因多态性与肺癌化疗敏感性关系的研究

目的：研究DNA修复基因XPD751基因多态性与肺癌化疗敏感性的关系。方法：收集经病理学确诊的肺癌234例，所有病例化疗前抽静脉血，提取白细胞DNA，用多聚酶链反应-限制性片段长度多态性（PCR—RFLP）分析技术检测XPD751基因型。所有患者均经铂类药物为基础的化疗方案治疗。结果：1）在24例肺癌患者中，XPD751 Lys／Lys、Lys／Gln和Gln／Gln基因型分别为192（82．1％）、40（17．1％）和2（0．8％）例。经化疗后，110例患者有效，总有效率为47．0％。2）XPD75 1Lys／Lys、Lys／Gln和Gln／Gln基因型有效率分别为50．0％（96／192）、30．0％（12／40）和100％（2／2），三者相比差异有统计学意义，Х^2=7．59，P=0．0225。在调整性别、年龄、临床分期、细胞学类型和化疗方案的影响后，发现携带XPD751 Lys／Gln基因型患者化疗失败的可能性是Lys／Lys基因型患者的2．28倍，OR=2．28，95％CI为1．05～4．91。3）携带Lys／Lys基因型患者的恶心呕吐反应和脱发程度均高于Lys／Gln和Gln／Gln基因型患者，Х^2值分别为4．504和4．011，P值分别为0．034和0．045。结论：XPD751基因多态性与肺癌对铂类药物为基础的化疗敏感性相关，检测XPD751基因型可以预测肺癌化疗的敏感性。     

The XPD Asp312Asn and Lys751Gln polymorphisms, corresponding haplotype, and pancreatic cancer risk

We evaluated the association between the XPD exon 10 Asp(312)Asn and exon 23 Lys(751)Gln polymorphisms and the risk of pancreatic cancer in a hospital-based study of 344 patients and 386 controls frequency matched by age, gender, and race. Stratified analyses showed ever smokers carrying the Asn(312)Asn genotype had a significantly reduced risk when compared with those carrying the (312)Asp allele (OR=0.46, 95% confidence interval 0.24-0.88) (P for interaction=0.03). The (312)Asp-(751)Gln was identified as the putative at risk haplotype. Our study shows that the XPD gene polymorphism could be a genetic risk modifier for smoking-related pancreatic cancer.     

Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population

Esophageal squamous cell carcinoma (ESCC), which is prevalent in China, is believed to be induced by environmental carcinogens. Accumulating evidence has shown that individual variation in DNA repair capacity resulting from genetic polymorphism influences risk of environmental carcinogenesis. We therefore investigated the associations between genetic polymorphisms in the DNA repair genes XRCC1 (Arg194Trp and Arg399Gln) and XPD (Asp312Asn and Lys751Gln) and risk of ESCC in an at-risk Chinese population. Genotypes were determined by a PCR-based approach in 433 patients with ESCC and 524 frequency-matched normal controls. We found that individuals with Trp/Trp genotype at XRCC1 Arg194Trp site had a 2-fold increased risk of this disease compared to Arg/Arg genotype (adjusted OR = 1.98; 95% CI 1.26-3.12). Furthermore, when compared to Arg/Arg and Arg/Trp genotype combined, homozygote for Trp/Trp genotype significantly increased the risk of developing ESCC, with the adjusted OR being 2.07 (95% CI 1.34-3.20). However, the XRCC1 Arg399Gln polymorphism was not significantly associated with risk of ESCC, with the adjusted OR being 0.87 (95% CI 0.55-1.37). Neither Asp312Asn nor Lys751Gln polymorphisms in the XPD gene influenced risk of ESCC in our study. These findings suggest that DNA repair gene XRCC1 but not XPD might play a role in esophageal carcinogenesis and might represent a genetic determinant in the development of the cancer.     

Polymorphisms of the DNA repair gene XPD and risk of lung cancer in a Chinese population

Previous studies suggested that suboptimal DNA repair capacity is associated with cancer risk and that the Asp312Asn and Lys751Gln polymorphisms in the xeroderma pigmentosum complementary group D (XPD) gene may influence DNA repair capacity. We therefore tested the hypothesis that these two XPD polymorphisms are associated with susceptibility to lung cancer in a hospital-based, case-control study in a Chinese population. Genotypes were determined by polymerase chain reaction-based restriction fragment length polymorphism methods in 383 healthy controls and 351 patients with lung cancer. We found that those who carried at least one 312Asn variant allele had an increased risk of squamous cell carcinoma (SCC) of the lung compared with those with the 312Asp/Asp genotype (adjusted odds ratio (OR), 1.80; 95% confidence interval (CI), 1.10-2.96). Compared with those having the 751Lys/Lys genotype, subjects carrying at least one variant 751 Gln allele were at a borderline increased risk of SCC of the lung (adjusted OR, 1.52; 95% CI, 0.94-2.46). Furthermore, stratified analysis suggested a multiplicative interaction between tobacco smoking and the Asp312Asn polymorphism on risk of SCC of the lung. The adjusted ORs of SCC of the lung for the variant XPD 312Asn genotype alone, for smoking > or = 29 pack-years alone, and for both the factors combined were 1.04 (95% CI, 0.37-2.94), 4.74 (95% CI, 2.88-9.49), and 14.32 (95% CI, 5.80-35.2), respectively. Similar results were evident for the Lys751Gln polymorphism that was in the linkage disequilibrium with the variant 312Asn allele. These data suggest that the two polymorphisms in the XPD gene may influence risk of smoking-related SCC of the lung.     

Genetic polymorphisms in DNA repair genes and risk of lung cancer

Polymorphisms in DNA repair genes may be associated with differences in the repair efficiency of DNA damage and may influence an individual's risk of lung cancer. The frequencies of several amino acid substitutions in XRCC1 (Arg194Trp, Arg280His and Arg399Gln), XRCC3 (Thr241Met), XPD (Ile199Met, His201Tyr, Asp312Asn and Lys751Gln) and XPF (Pro379Ser) genes were studied in 96 non-small-cell lung cancer (NSCLC) cases and in 96 healthy controls matched for age, gender and cigarette smoking. The XPD codon 312 Asp/Asp genotype was found to have almost twice the risk of lung cancer when the Asp/Asn + Asn/Asn combined genotype served as reference [odds ratio (OR) 1.86, 95% confidence interval (CI), 1.02-3.40]. In light cigarette smokers (less than the median of 34.5 pack-years), the XPD codon 312 Asp/Asp genotype was more frequent among cases than in controls and was associated with an increased risk of NSCLC. Compared with the Asn/Asn carriers, the OR in light smokers with the Asp/Asn genotype was 1.70 (CI0.35 0.43-6.74) and the OR in those with the Asp/Asp genotype was 5.32 (CI0.35-21.02) (P trend = 0.01). The 312 Asp/Asp genotype was not associated with lung cancer risk in never-smokers or heavy smokers (>34.5 pack-years). The XPD-312Asp and -751Lys polymorphisms were in linkage disequilibrium in the group studied; this finding was further supported by pedigree analysis of four families from Utah. The XPD 312Asp amino acid is evolutionarily conserved and is located in the seven-motif helicase domain of the RecQ family of DNA helicases. Our results indicate that these polymorphisms in the XPD gene should be investigated further for the possible attenuation of DNA repair and apoptotic functions and that additional molecular epidemiological studies are warranted to extend these findings.     

Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions

BACKGROUND: Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001-2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions. METHODS: Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULT: No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65-1.15) Asn/Asn (adjusted OR = 0.76, 95% CI = 0.50-1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95% CI = 0.69-1.23) Gln/Gln (adjusted OR = 0.98, 95% CI = 0.66-1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR = 0.45, 95% CI = 0.29-0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR = 0.47, 95% CI = 0.31-0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. CONCLUSION: XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an arsenic exposed population. Further study is necessary to explore the effect of XPD polymorphisms and sun exposure on risk of arsenic-related skin lesions.     

Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population

Variation in DNA repair capacity, which is believed to be largely determined by genetic traits, is linked to risk of certain cancers. The Asp312Asn and Lys751Gln polymorphisms in the xeroderma pigmentosum complementary group D (XPD) gene may alter DNA repair capacity. We thus examined the hypothesis that these 2 XPD polymorphisms are associated with risk of lung cancer via a large hospital-based, case-control study among Chinese. The study subjects consisted of 1,006 patients with primary lung cancer and 1,020 age- and sex-matched population controls. XPD genotypes were determined using PCR-RFLP techniques, and the associations between genotypes and risk of lung cancer were estimated by odds ratios (ORs) and their 95% confidence intervals (CIs) calculated by unconditional logistic regression. Subjects homozygous for the 312Asn/Asn genotype had an increased risk of lung cancer (adjusted OR = 10.33, 95% CI = 1.29-82.50) compared with subjects homozygous for the 312Asp/Asp genotype. The 751Gln/Gln genotype was also associated with increased risk for the cancer compared with the 751Lys/Lys genotype (adjusted OR = 2.71, 95% CI = 1.01-7.24). Stratification analysis revealed that the increased risk was mainly confined to lung squamous cell carcinoma, with the ORs being 20.50 (95% CI = 2.25-179.05) for the 312Asn/Asn genotype and 4.24 (95% CI = 1.34-13.38) for the 751Gln/Gln genotype, respectively. Haplotype analysis with the 2 polymorphisms suggested these polymorphisms might be in linkage disequilibrium with a different causative locus or act together with other functional variants in or close to the XPD locus.