DNA修复基因XRCC1多态与食管癌TNM分期及区域淋巴结转移的相关性研究

目的 研究DNA修复基因XRCC1 Arg194Trp和Arg399Gln多态与食管鳞状细胞癌临床病理TNM分期及区域淋巴结转移的相关性,探讨其对食管癌临床表型的影响.方法 以PCR和PCR-RFLP方法分析了182例食管癌病人的上述基因多态,比较不同TNM分期及区域淋巴结转移的食管癌病人各基因型频率分布的差异.结果 食管癌Ⅱb～Ⅳ期及有区域淋巴结转移病人XRCC1Arg194Trp基因型及Arg399Gln基因型频率与0～Ⅱa期及无区域淋巴结转移病人虽有差别,但无统计学意义.食管癌区域淋巴结转移病人携带XRCC1194Arg/Trp杂合型和399Arg/Arg野生型基因型频率为32.3%,显著高于携带XRCC1194Arg/Arg基因型的20.0%（P=0.01）.结论 DNA修复基因XRCC1多态中携带194变异型基因型和399野生型基因型的病人区域淋巴结转移率较高,病变进展较快,因此与食管癌TNM分期和区域淋巴结转移存在相关型,两者对食管癌病人的预后有影响.     

X射线损伤修复交叉互补基因1 Arg399Gln、Arg280His和Arg194Trp位点多态性与胃癌易感性的相关性分析

目的探讨X射线损伤修复交叉互补基因1(XRCC1)Arg399Gln、Arg280His和Arg194Trp位点多态性与胃癌易感性的关系。方法选取120例胃癌患者(胃癌组)与120名健康体检自愿者(对照组)作为正常对照进行对比研究。取外周血提取DNA,采用聚合酶链反应-限制性片段长度多态性技术对XRCC1 Arg399Gln、Arg280His和Arg194Trp位点基因多态性进行检测分析,分析不同基因型与胃癌易感性的关系。结果 1 2组在性别、年龄、吸烟、饮酒、饮食特点等常见暴露因素比较差异均无统计学意义(P0.05)。2胃癌组患者的XRCC1基因194位点Arg/Arg多态基因型出现频率低于对照组(P0.05),Arg/Trp、Trp/Trp多态基因型及Arg/Trp+Trp/Trp变异基因型出现频率均明显高于对照组(P0.05)。3胃癌组患者的XRCC1基因280和399位点多态基因型及变异基因型出现频率与对照组比较差异均无统计学意义(P0.05)。结论从本研究结果初步得出,XRCC1 Arg399Gln和Arg280His位点多态性与胃癌易感性无关,而Arg194Trp位点多态性与胃癌的易感性有关。     

苏、皖地区汉族人群DNA修复基因XRCC1 Arg399Gln多态性与前列腺癌易感性的关系

目的:研究中国苏、皖汉族人群DNA修复基因X线修复交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)Arg399Gln多态性,并探讨其在吸烟、饮酒与前列腺癌易感性关系中的影响。方法:采用病例-对照研究,提取207例前列腺癌患者(病例组)和235例非肿瘤、非前列腺疾病患者(对照组)外周血中基因组DNA,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析病例组和对照组的XRCC1基因Arg399Gln位点的多态性,比较不同基因型与前列腺癌易感性的关系,并探讨吸烟、饮酒等因素在其中的影响。结果:XRCC1第399密码子Arg/Gln基因型的个体其前列腺癌发病风险是Arg/Arg基因型的1.55倍(OR=1.55,95%CI:1.01~2.39),携带399Gln等位基因(Arg/Gln及Gln/Gln)的个体发生前列腺癌的风险性是Arg/Arg基因型的1.61倍(OR=1.61,95%CI:1.07~2.44)。在重度吸烟(吸烟指数≥20)人群中,携带399Gln等位基因的个体发生前列腺癌的风险性是Arg/Arg基因型的1.94倍(OR=1.94,95%CI:1.02~3.71)。在浅吸烟(吸烟仅入嘴中)人群中,携带399Gln等位基因的个体发生前列腺癌的风险性是Arg/Arg基因型的2.44倍(OR=2.44,95%CI:1.02~5.80)。结论:XRCC1 Arg399Gln位点多态性可能对前列腺癌遗传易感性产生影响,Arg/Gln、Gln/Gln可能是前列腺癌的易感基因型,并和吸烟在前列腺癌的发病中有一定的协同作用。     

修复基因XRCC1Arg194Trp位点多态性与结直肠癌易感性的相关性分析

目的探讨DNA损伤修复基因XRCC1Arg194Trp位点多态性与结直肠癌易感性的关系。方法选取120例结直肠癌患者与120例正常对照者进行对比研究。取外周血提取DNA,采用限制性片段长度多态性聚合酶链反应（PCR-RFLP）技术对XRCC1Arg194Trp基因多态性进行检测分析,比较不同基因型与结直肠癌易感性的关系。结果2组观察对象在年龄、性别、吸烟、饮酒、饮食特点等常见暴露因素方面的差异均无统计学意义（P〉0．05）,变异基因型Arg／Trp＋Trp／Trp出现频率在2组观察对象中分别为30．00％和24．17％,差异无统计学意义（P〉0．05）。结论XRCC1Arg194Trp位点多态性与结直肠癌的易感性并无显著相关性。     

人类XRCC1-399单核苷酸多态性与原发性肝细胞癌的相关研究

目的以病例-对照研究方式探讨人类DNA修复基因XRCC1-399单核苷酸多态性(SNP)与HBV感染者的原发性肝细胞癌(HCC)的发生关系.方法72例HCC患者经病理检查证实,根据地缘、性别、年龄,按1:1～2比例匹配137例非HCC对照者.采用聚合酶链反应-限制片段长度多态性(PCR-RFLP)技术检测受试者XRCC1-399位SNP.结果(1)XRCC1-399SNP和年龄均与HCC的发生无关,但在XRCC1-399Arg/Arg受试者中,HCC的发生与年龄呈负相关(P=0.028);(2)HBV感染是HCC发生的肯定因素(P=0.007);在XRCC1-399Gln/Gln或Arg/Gln受试者中,伴HBV感染者HCC发生率(25.7%)远高于不伴HBV感染者(5.3%,P=0.047);(3)XRCC1-399Arg/Arg受试者HBV感染率与Gln/Gln或Arg/Gln受试者近似(36.6%对38.0%,P=0.052).结论(1)XRCC1-399Arg/Arg可能具有潜在抵抗HCC发生的作用;(2)XRCC1-399Gln/Gln或Arg/Gln联合HBV感染是HCC发生的高危因素.     

X射线损伤修复交叉互补基因1的单核苷酸多态性与散发性结直肠癌易感性相关

目的 检测单核苷酸多态性（SNP）位点Arg399Gln在散发性结直肠癌患者和非癌对照组中的分布情况，分析其与散发性结直肠癌及其临床病理特征的相关性。方法 从178例肿瘤组织和非癌对照组的180例血样中提取DNA，采用Taqman探针技术检测Arg399Gln多态性表型，并用统计软件计算各基因型的比值比（OR）和95％可信区间（95％CI）。结果 肿瘤组与对照组就XRCC1Arg399Gln多态性的基因表型差异有统计学意义（P〈0．05）；年龄不超过60岁的患者和超过60岁的患者在该位点的基因型差异有统计学意义（P〈0．05）；以399Arg／Arg基因型为参照，在年龄超过50岁的人群中（OR=0．64，95％C10．50～0．83，P〈0．05）和男性人群中（OR=0．64，95％C10．51～0．79，P〈0．05）携带至少一个Gin等位基因可致罹患散发性结直肠癌的风险显著降低；XRCC1399SNP与患者性别及散发性结直肠癌的发生部位、Dukes分期、浸润深度、淋巴结转移以及病理分型均无显著相关性（P均〉0．05）。结论 XRCC1399SNP可能通过改变DNA的损伤修复功能，成为散发性结直肠癌的易感因素。     

DNA修复基因XRCC1多态与食管癌遗传易感性

目的 探讨DNA修复基因XRCCl多态与食管癌遗传易感性的关系.方法 采用病例一对照分子流行病学方法,分析182例食管癌病人和375例正常对照的XRCCl基因型分布,比较其不同基因型与食管癌风险的关系.结果 多因素回归分析表明,XRCCl194Trp基因型与食管癌风险增高相关(校正OR 1.86;95%CI 1.19～2.88),特别是重度吸烟者;XRCClArg399Gln基因型分布差异无统计学意义(P>0.05),因而与食管癌风险无关.结论 DNA修复基因XRCCl多态与食管癌风险相关.     

手术切除的非小细胞肺癌XRCC1和TYMS基因多态性检测结果分析

目的 总结分析手术切除的非小细胞肺癌患者肿瘤组织标本XRCC1基因399密码子多态性检测、TYMS基因5'非翻译区增强子序列多态性检测表达规律,探讨其在指导手术切除的非小细胞肺癌以术后化疗个体化为目的肿瘤标志物联合检测中的临床意义.方法 回顾性总结分析首都医科大学附属北京友谊医院胸外科2010年2月-2014年6月150例NSCLC患者手术切除的肿瘤组织XRCC1和TYMS基因多态性检测结果.应用SPSS 21.0进行统计分析.结果 XRCC1 399基因型常见的有Arg/Arg、Arg/Gln和Gln/Gln,分别为88例(58.7％)、55例(36.7％)和7例(4.6％).TYMS携带5'-UTR串联重复序列常见的是3R/3R、2R/3R和2R/2R基因型分别为106例(70.7％)、38例(25.3％)和6例(4.0％).结论 手术切除的NSCLC中,XRCC1 399基因型Arg/Arg最为常见,其次为Arg/Gln型;TYMS基因型3R/3R占70％以上,尤其是腺癌中比例更高.不建议将XRCC1 399 Arg/Gln基因型作为排除铂类化疗的标志物,同时也不建议将TYMS 3R/3R基因型作为排除培美曲塞化疗的标志物.     

DNA修复基因多态性与非肌层浸润性膀胱癌易感性的相关性

目的 探讨上海地区汉族人群中DNA修复基因多态性与非肌层浸润性膀胱癌遗传易感性的关系. 方法 采用Taqman探针实时荧光定量PCR技术、病例对照研究方法,采集研究对象外周静脉血,检测94例病理证实原发非肌层浸润性膀胱癌患者和304例非肿瘤对照者的3个DNA修复基因(XPC,XPG,XRCC1)中的3个单核苷酸多态性位点.应用非条件Logistic回归模型,调整混杂因素后,分析各基因型与非肌层浸润性膀胱癌发生的关系以及与肿瘤临床病理特征之间的关系. 结果 膀胱癌组的XPC 939 Lys/Gln和XPC 939Gln/Gln基因型频率(70.0%,63/90)显著高于对照组(60.9%,185/304),XPG 1104 Asp/His和XPG 1104 His/His基因型频率(79.2%,57/72)亦高于对照组(73.0%,203/278).调整性别、年龄、吸烟等因素后,XPC 939 Lys/Gln和XPC939Gln/Gln基因型频率在膀胱癌患者中明显增高(校正OR为1.89,95%CI 1.14～3.23,P=0.02);XPG 1104 Asp/His和XPG 1104 His/His基因型频率在膀胱癌患者中轻度增高(校正OR为1.07,95%CI 0.86～1.87,P=0.048).XRCC1 Arg399Gln多态性与膀胱癌无关性(校正OR为1.15,95%CI 0.55～2.40,p=0.27).XPC和XPG多态性与肿瘤临床病理特征之间均无相关性(P>0.05).结论 XPC Lys939Gln和XPG Asp1104His基因多态性与上海地区汉族人群非肌层浸润性膀胱癌易感性有关.     

Association of XRCC1 gene polymorphisms with idiopathic azoospermia in a Chinese population

Aim： To assess the possible role of genetic polymorphisms in DNA repair gene XRCC 1 （X-ray repair cross-comple- menting group l） during spermatogenesis by investigating the associations of one promoter polymorphism （T-77C） and two exonic polymorphisms （Argl94Trp and Arg399Gln） in XRCC1 gene with risk of idiopathic azoospermia in a Chinese population. Methods： The genotype and allele frequencies of three observed polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism based on a Chinese population consisting of 171 idiopathic azoospermia subjects and 247 normal-spermatogenesis controls. Results： In our study, all the observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium. The 399A （GA＋AA） allele frequency for idiopathic azoospermia subjects and controls was 0.216 and 0.269, respectively. Compared with GG genotype, the AA genotype of Arg399Gln showed a significant association with a decreased risk of idiopathic azoospermia （odds ratio = 0.315; 95% confidence interval = 0.12-0.86）. However, no significant differences were found between the cases and controls for T-77C and Arg194Trp polymorphisms. The major haplotypes of XRCC1 gene were TCG, TrG and TCA, whereas no haplotypes appeared to be significantly associated with idiopathic azoospermia based on the cutoff of P 〈 0.05. Conclusion： In a selected Chinese population, AA genotype of Arg399Gln appears to contribute to a decreased risk of idiopathic azoospermia, while we have not any evidence of involvement of XRCC1 T-77C and Arg194Trp polymorphisms in idiopathic azoospermia. （Asian J Androl 2007 Nov; 9： 843-848）     

Relationship between XRCC1 polymorphisms and susceptibility to prostate cancer in men from Han, Southern China

Aim： To investigate the association among XRCC1 polymorphisms, smoking, drinking and the risk of prostate cancer （PCa） in men from Han, Southern China. Methods： In a case-control study of 207 patients with PCa and 235 cancerfree controls, frequency-matched by age, we genotyped three XRCC1 polymorphisms （codons 194, 280 and 399） using the polymerase chain reaction-restriction fragment length polymorphism （PCR-RELP） method. Results： Among the three polymorphisms, we found that the XRCC1 Arg399Gln variant allele was associated with increased PCa risk （adjusted odd ratio [OR]： 1.67, 95% confident interval [CI]： 1.11-2.51）, but the XRCC1 Arg 194Trp variant allele had a 38% reduction in risk of PCa （adjusted OR： 0.62, 95% CI： 0.41-0.93）. However, there was no significant risk of PCa associated with Arg280His polymorphism. When we evaluated the three polymorphisms together, we found that the individuals with 194Arg/Arg wild-type genotype, Arg280His and Arg399Gln variant genotypes had a significantly higher risk of PCa （adjusted OR： 4.31; 95% CI： 1.24-14.99） than those with three wild-type genotypes. In addition, we found that Arg399Gln variant genotypes had a significant risk of PCa among heavy smokers （adjusted OR： 2.04; 95% CI： 1.03-4.05）. Conclusion： These results suggest that polymorphisms of XRCC1 appear to influence the risk of PCa and may modify risks attributable to environmental exposure.     

XRCC1 Arg399Gln and Arg194Trp polymorphisms in prostate cancer risk: a meta-analysis

Epidemiological studies have evaluated the association between X-ray repair cross-complementing group 1 gene (XRCC1) Arg399Gln and Arg194Trp polymorphisms and risk of prostate cancer (PCa). However, the results from the published studies on the association between these two XRCC1 polymorphisms and PCa risk are conflicting. To derive a more precise estimation of association between the XRCC1 polymorphisms and risk of PCa, we performed a meta-analysis. A comprehensive search was conducted to identify all case-control studies of XRCC1 polymorphisms and PCa risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both Arg399Gln and Arg194Trp polymorphisms were not significantly associated with PCa risk. However, in stratified analysis by ethnicity, we found that the Arg399Gln polymorphism was significantly associated with PCa risk in Asian population (Gln/Gln vs Arg/Arg: OR=1.46, 95% CI: 1.05-2.03, P=0.03; Gln/Gln vs Arg/Gln+Arg/Arg: OR=1.48, 95% CI: 1.12-1.95, P=0.01). In this meta-analysis, we found that both Arg399Gln and Arg194Trp polymorphisms were not related to overall PCa risk. However, in subgroup analysis we found a suggestion that XRCC1 399Gln allele might be a low-penetrent risk factor for PCa only in Asian men.     

Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans

PURPOSE: XRCC1 and APE1 are enzymes involved in the repair of DNA strand breaks and base damage that arise from various endogenous and exogenous oxidants. We determined whether polymorphisms in XRCC1 and APE1 increase the risk of prostate cancer. MATERIALS AND METHODS: We performed a case-control study in 228 white American men, 124 black American men, and 335 age, sex and race matched controls. Polymorphisms at codon 399 in XRCC1, and at codons 51 and 148 in APE1 were determined using an restriction fragment length polymorphism method. Frequencies were compared between cases and controls. RESULTS: A significantly increased risk of prostate cancer was observed in white men with the XRCC1(399Gln) allele (OR 1.6, 95% CI 1.1 to 2.4). When APE1 and XRCC1 polymorphisms were evaluated together, we found an increased risk of the XRCC1(399Arg/Gln+Gln/Gln)/APE1(51Gln/Gln) (OR 4.0, 95% CI 1.3 to 12.5) and XRCC1(399Arg/Gln+Gln/Gln)/APE1(148Asp/Asp) (OR 2.9, 95% CI 1.4 to 6.1) genotypes in white men. Significant associations were found between combined genotypes and prostate cancer risk with a dose-effect relationship in white men (trend test p = 0.035 and 0.039, respectively). No significant associations were observed between polymorphisms in these genes and prostate cancer risk in black men. CONCLUSIONS: Our results suggest that inherited variability in DNA repair capacity, as reflected by polymorphisms in XRCC1 and APE1, is a risk factor for prostate cancer.     

DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in Egyptian population

Abstract

DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to end-stage renal disease (ESRD). We aimed to determine the association of polymorphisms in xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1) with ESRD development. Polymorphisms in XPD codons 312 and 751 and XRCC1 codon 399 were genotyped in 98 patients undergoing hemodialysis and 102 healthy controls using polymerase chain reaction and restriction fragment length polymorphism. Patients having XRCC1-399 Arg/Gln genotype or XRCC1-399 Gln/Gln genotype had a significantly higher risk of ESRD than those with XRCC1-399 Arg/Arg [odds ratio (OR): 2.48; 95% confidence intervals (CI): 1.36–4.52; p?=?0.004 and OR: 4.05; 95% CI: 1.19–13.73; p?=?0.03, respectively]. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls (OR: 2.22; 95% CI: 1.16–4.25; p?=?0.02). Combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with Asp/Asn or Asn/Asn genotypes of XPDAsp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. Haplotypes association showed that association of Gln allele of XRCC1 Arg399Gln polymorphism with the Asn allele of XPDAsp312Asn polymorphism (p?=?0.004) or Gln allele of XRCC1 Arg399Gln polymorphism with the Gln allele of XPD Lys751Gln polymorphism (p?=?0.003) was highly significantly associated with the development of ESRD. This study revealed that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of ESRD. Furthermore, larger studies should be conducted to confirm these results.     

XRCC1 gene polymorphisms and breast cancer risk in different populations: A meta-analysis

We performed a meta-analysis to investigate the role of XRCC1 polymorphisms Arg194Trp, Arg280His and Arg399Gln in breast cancer. The results were pooled in a manner that appropriately reflects a biological model of gene effect using a random effects logistic regression model without multiple comparisons. Forty studies from 31 reports were included with 10 465 cases and 10 888 controls at Arg194Trp, 6156 cases and 5806 controls at Arg280His, and 21 467 cases and 22 766 controls at Arg399Gln. Our analysis found a tendency towards a recessive effect of Arg280His variant in Asian population only (His/His vs. Arg/Arg + Arg/His: OR = 2.27, 95% CI = 0.82, 6.31). An increased breast cancer risk with a recessive effect was also suggested for Arg399Gln variant in Asian population (Gln/Gln vs. Arg/Arg + Arg/Gln: OR = 1.59, 95% CI = 1.22, 2.09) only. These findings suggest that polymorphisms Arg280His and Arg399Gln may modify breast cancer risk differently in Caucasian and Asian populations.     

DNA损伤修复基因XRCC1 Arg194Trp基因多态性与中国人群结直肠癌易感性的Meta分析

【摘要】 目的 探讨DNA损伤修复基因XRCC1 Arg194Trp基因多态性与中国人群结直肠癌易感性的关系。方法 按照制定的检索策略,通过计算机和手工检索相关数据库,收集有关XRCC1 Arg194Trp基因多态性与中国人群结直肠癌易感性的病例对照研究,按照纳入标准筛选文献、并从纳入文献中提取相关数据,以病例组和对照组基因型分布的比值比(OR)为效应指标,应用Stata12.0软件进行异质性检验,对各研究原始数据进行Meta合并,并行敏感性分析和发表偏倚的评估。结果〓本Meta分析共纳入11项病例对照研究,累积病例2710例,对照3567例。根据各研究间的异质性,采用不同的模型进行合并效应量。在等位基因比较(T vs C) [OR(95%CI)=1.18(1.01-1.39),P=0.036],纯合子比较模型(TT vs CC) [OR (95%CI)=1.39(1.02-1.90),P=0.038],显性模型(CT/TT vs CC) [OR(95%CI)=2.24(1.78-2.82),P<0.001] 以及隐性模型 (TT vs CT/CC) [OR(95%CI)=1.23(1.02-1.49),P=0.030]均存在显著的统计学差异。发表偏倚评估均未见明显偏倚。结论〓在中国人群中,携带突变等位基因T或突变纯合子TT的人群罹患CRC的风险有所升高,而在显性遗传模型中,携带有CT/TT基因型的人群其CRC的易感性明显升高。     

Single-Nucleotide Polymorphisms of DNA Repair Genes OGG1 and XRCC1: Association with Gallbladder Cancer in North Indian Population

Background  DNA damage by endogenous or exogenous source of reactive oxygen species (ROS) plays an important role in induction and progression of various cancers. Physiologically, gallbladder is likely to be exposed to various ROS which leads to extensive DNA damage. Cells overcome the DNA damage by repair mechanisms. Genetic variants of OGG1 and XRCC1, important enzymes participating in base excision repair pathway, may confer interindividual variations in susceptibility to gallbladder cancer (GBC). This study was aimed to examine the role of OGG1 Ser326Cys (rs1052133) and XRCC1 Arg194Trp (C > T) (rs25487) and Arg399Gln (G > A) (rs1799782) polymorphisms in GBC susceptibility. Methods  The study included 173 GBC patients and 204 controls. Genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Differences in the frequencies were estimated by chi-square test and risk was estimated by using unconditional logistic regression after adjusting for age and gender. Results   OGG1 Cys/Cys genotype frequency was significantly higher in GBC patients [odds ratio (OR) = 2.93; 95% confidence interval (CI) = 1.14–7.51]. The increased risk was more pronounced in female GBC patients (OR = 5.92; 95%CI = 1.20–29.13), patients with gallstone (OR = 5.50; 95%CI = 1.99–15.16), female gender, and late onset of disease (OR = 4.72, 95%CI = 1.43–15.53). In XRCC1 Arg399Gln polymorphism, significant differences in frequencies of Gln/Gln and Arg/Gln genotypes conferred significantly low risk for GBC (OR = 0.62; 95%CI = 0.39–0.97 and OR = 0.37; 95%CI = 0.19–0.71 respectively). However, XRCC1 Arg194Trp polymorphism was not associated with GBC. The carriers of Arg-Gln haplotype consisting of 194Arg and 399Gln alleles of XRCC1 were also at significant low risk for GBC (OR = 0.59, 95%CI = 0.42–0.82). Interaction of genotypes and tobacco usage did not modulate the risk. Conclusion  Results suggest that Cys/Cys genotype of OGG1 Ser326Cys polymorphism is associated with increased risk of GBC. However, Arg399Gln polymorphism and Arg-Gln haplotype comprising XRCC1 Arg194Trp and Arg399Gln polymorphisms conferred low risk for GBC susceptibility.