XPC基因多态性与男性不育的相关性研究

目的:位于XPC基因外显子区域Ala499Val(C>T)和Lys939Gln(A>C)两个非同义突变的单核苷酸多态性位点在人群中研究广泛,具有潜在的功能性,其多态的变化影响到XPC基因的结构和功能,进而影响到DNA损伤修复率。本文探讨了这两个位点基因多态性在中国汉族人群中的分布及其与男性不育发病风险的关联。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,分析318例男性不育患者和228例正常对照男性中XPC基因两个多态性位点的基因分型和等位基因频率,以及这两个位点单独和联合作用与男性不育的相关性。结果:在Ala499Val(C>T)多态性位点中,CC、CT、TT三种基因型频率在病例和对照组中的分布存在显著性差异(P=0.020)。携带TT基因型的个体罹患男性不育的风险是CC基因型个体的0.49倍(95%CI=0.23～0.88),是(CC+CT)基因型个体的0.39倍(95%CI=0.22～0.71)。Lys939Gln(A>C)多态性位点与男性不育的患病风险无显著性关联。联合两个位点分析,个体携带1～4个危险位点患男性不育的风险是携带零个的2.75倍(95%CI=1.50～5.04)。结论:XPC基因Ala499Val(C>T)基因多态性与男性不育的发病风险存在关联,可能是我国汉族人群男性不育的遗传易感因素之一。     

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。     

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。     

结直肠癌患者的DNA修复基因XRCC1单核苷酸多态研究

目的 探讨DNA碱基切除修复基因XRCC1单核苷酸多态与结直肠癌易感性的关系.方法 采用病例-对照分子流行病学方法,以聚合酶链反应-限制性酶切片段多态性(PCRRFLP)方法分析120例结直肠癌患者和150例正常对照XRCC1基因单核苷酸多态Arg194Trp和Arg399Gln的基因型分布,并比较不同基因型与结直肠癌风险的关系.结果 正常人群中194Arg/Arg、Arg/Trp和Trp/Trp基因型频率分别为52.0%、42.0%和6.0%,而结直肠癌患者中分别为40.8%、46.7%和12.5%,分布差异有统计学意义(P＜0.05,趋势检验).与携带野生基因型Arg/Arg者比较,携带Trp/Trp基因型个体患结直肠癌的风险降低了1. 43倍(校正OR=2.43;95%CI=1.10～5.92).而194Arg/Trp基因型和Arg399Gln遗传多态则与结直肠癌风险无关.结论 DNA修复基因XRCC1 Arg194Trp多态可能是结直肠癌发生的遗传易感因素.     

GSTM1基因多态性和膀胱癌遗传易感性的关系

目的探讨GSTM1基因多态性与膀胱癌遗传易感性的关系. 方法采用PCR技术,以病例-对照研究方法,对69例膀胱癌患者和88例健康对照者的GSTM1基因型进行检测. 结果膀胱癌患者GSTM1空白基因型频率为58%,对照组为41%,两组比较差别有显著性意义(χ2=4.51,P<0.05),OR值为2.0(95%CI=1.05～3.79).吸烟者中,患者组GSTM1空白基因型频率为71%,对照组为24%,两组比较差别有显著性意义(χ2=22.6,P<0.01),OR值为8.3(95%CI=3.34～20.65).以GSTM1非空白型/不吸烟者为参照,GSTM1空白型/吸烟者的OR值为4.64(95%CI=1.86～11.37,χ2=11.63,P<0.01),差别有显著性意义. 结论 GSTM1基因多态性与膀胱癌易感性有关,在膀胱癌的发生发展中与吸烟协同起作用.     

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.     

修复基因XRCC4多态性与膀胱癌易感性的Meta分析

目的 探讨XRCC4单核苷酸多态性与膀胱癌发病易感性的关联。方法 通过检索PubMed、CNKI和万方数据库,检索从1960年1月1日至2015年12月31日国内外已经公开发表的中、英文献,筛选合格文献行Meta分析。结果 最终纳入关于XRCC4基因多态性与膀胱癌易感性关联的病例-对照研究10项,计病例组2 689例,对照组2 915例。Meta分析结果显示,XRCC4基因rs28360317和rs1805377多态性位点与膀胱癌显著相关(rs28360317:B vs.A:OR=1.339,95%CI:1.088~1.649,P=0.006;BBvs.AA:OR=1.729,95%CI:1.137~2.629,P=0.010;BBvs.BA+AA:OR=1.638,95%CI:1.144~2.346,P=0.007;rs1805377:BAvs.AA:OR:1.242,95%CI:1.041~1.482,P=0.016;BA+BB vs.AA:OR=1.216,95%CI:1.023~1.445,P=0.027。以种族为依据的亚组分析揭示,XRCC4基因rs1805377多态性在高加索人群中与膀胱癌发病显著相关:B vs.A:OR=1.295,95%CI:1.070~1.566,P=0.008;BAvs.AA:OR=1.362,95%CI:1.101~1.684,P=0.004;BA+BB vs.AA:OR=1.348,95%CI:1.096~1.659,P=0.005。然而,XRCC4基因rs6869366和rs28360071多态性位点与膀胱癌的易感性无关。结论 XRCC4基因rs28360317和rs1805377单核苷酸多态性与膀胱癌发病风险呈显著正相关,可作为膀胱癌患者潜在诊断、筛查分子标志物。     

膀胱癌易感性与髓过氧化物酶基因-463G>A 多态性的关系

目的 探讨髓过氧化物酶(MPO)基因-463G＞A多态性与中国苏皖地区汉族人群膀胱癌易感性的关系.方法 采用面访填写调查表及采用聚合酶链反应.限制性片段长度多态性(PCR-RFLP)方法 检测年龄和性别匹配的中国苏皖地区汉族354例膀胱癌患者和360例正常人群的MPO一463G＞A基因型.通过分层分析探讨年龄、性别和吸烟对罹患膀胱癌的影响.结果 与-463GG比较,携带MPO-463GA/AA基因型者可降低罹患膀胱癌的危险性(OR=0.72,95%CI=0.54-0.99).分层分析结果显示,年龄60岁的男性在吸烟下携带-463GA/AA基因型具有保护作用(年龄60岁:OR=0.37,95%CI=0.22-0.61;男性:0.66,95%CI=0.47-0.97;吸烟:0.64,95%CI:0.41-0.99).结论 MPO-463G＞A多态性可能与我国苏皖地区汉族人群膀胱癌发生有关.     

胃癌发生与XPC基因单倍型的关系

目的 探讨XPC基因多态性位点rs2228000和rs2228001位点与胃癌发生风险的关系.方法 采用聚合酶链反应.限制性片段长度多态性(PCR-RFLP)方法,对203例胃癌患者和210例对照者进行XPC基因rs2228000位点和rs2228001位点多态性检测;并采用PHASE 2.0软件构建这两个多态性位点的单倍型,以非条件Logistic回归校正混杂因素,进行多态性与胃癌风险相关性的统计学分析.结果 XPC基因多态性位点rs2228000与rs2228001在胃癌与正常对照组之间差异无统计学意义(P>0.05).该两个SNPs构建的单倍型AT与CT与胃癌的易感关联的差异有统计学意义(P<0.01),OR值分别为2.62,10.51;分层分析显示AT与cT单倍型在性别、吸烟、饮酒、年龄分层中的差异均有统计学意义(P<0.05),且在AT单倍型中随年龄的增大,OR值逐渐增高,在<50岁、50～60岁、>60岁3个年龄层中OR值分别为1.91(95%CI:1.08～3.38)、3.49(95%CI:1.50～8.15)、5.43(95%CI:1.58～18.67).结论 XPC基因rs2228000与rs2228001多态性位点的单倍型与胃癌的发生明显相关.     

X线交错互补修复基因1和核苷酸剪切修复基因多态性与前列腺癌发病风险的相关性

目的 探讨DNA损伤修复基因X线交错互补修复基因1(XRCCI)、核苷酸剪切修复基因(XPD)基因多态性与前列腺癌发病风险的关系. 方法 以358例前列腺癌患者和312例健康对照者为研究对象,采用聚合酶链反应一限制性片段长度多态技术检测XRCC1 C26304T、G28152A和XPD A35931C位点基因型,以非条件logistic回归分析计算比值比(OR)及95%可信区间(CI),评估不同基因型与前列腺癌风险之间的相关性. 结果 前列腺癌组XRCC1 28152位点AA基因型者47例(13.1%),对照组24例(7.1%),携带此基因型者患前列腺癌风险显著增加(OR 1.924,95%CI=1.126～3.288,P=0.017).2组间XRCC1 C26304T和XPD A35931C位点基因型分布差异无统计学意义.3个基因位点联合分析结果 显示,个体携带XRCCI 28152AA型及XPD 35931AC+CC型者发生前列腺癌风险显著增加(OR=3.087,95%CI 1.081～8.813;OR=3.376,95%CI 1.067～10.683,OR 3.216,95%CI=1.439～7.188,P=0.004).以患者年龄、PSA值、Gleason评分以及临床分期分层分析结果 显示,携带XRCC1 28152AA及XPD 35931AC+CC基因型者发病年龄明显低于携带野生基因型者(P<0.05). 结论 中国汉族人群XRCCl和XPD基因多态与前列腺癌发病有关,尤其是较年轻者.     

Estudio sobre susceptibilidad de cáncer de vejiga y polimorfismos genéticos de XPC,XPG y CYP en fumadores y no fumadores

ObjectiveTo investigate the gene susceptibility of bladder cancer and potential relation with smoking.Material and methodsAn analysis of SNPs were conducted among DNA repair genes of XPC, XPG, XRCC1, and six members of metabolic enzyme gene CYP 450 via TaqMan Probe-based polymerase chain reaction. A total of 130 patients with bladder cancer and 304 healthy controls were involved.ResultsPolymorphisms of XPC gene was related to bladder cancer. It was also related to smoking status in bladder cancer patients, as well as to tumour stage, male gender and older age. The XPG gene polymorphism was also related to bladder cancer yet it was prevalent in female non-smokers. No association was acquired for XRCC1 gene. The combination of more than 2 polymorphisms in DNA repair genes was associated with bladder cancer. No association was obtained in any of the metabolic enzyme gene of CYP450 with either bladder cancer or smoking status.ConclusionDNA repair genes XPC and XPG could be related to carcinogenesis and tumour progression of bladder cancer. Confirmation within larger population was warranted.     

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.     

XPC gene polymorphisms and risk of idiopathic azoospermia or oligozoospermia in a Chinese population

A retrospective case–control study was carried out in the Han-Chinese population to determine the polymorphisms of xeroderma pigmentosum complementation group C ( XPC ) gene on the risk of idiopathic azoospermia or oligozoospermia. The Ala499Val (C>T) and Lys939Gln (A>C) polymorphism of XPC gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism in three groups of infertile men (172 patients of azoospermia, 25 patients of severe oligozoospermia, 55 patients of oligozoospermia) and 228 fertile men. Increased risk of idiopathic azoospermia, but not oligozoospermia was associated with the XPC variant genotypes of Ala499Val (C>T) [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.04–2.68 for CT heterozygote and adjusted OR = 2.03, 95% CI = 1.10–3.75 for TT homozygote] compared with CC homozygous wide-type. The Lys939Gln (A>C) polymorphism was not related to spermatogenic failure. The combined risk alleles analysis and haplotype analysis showed that ORs increased as the number of the risk alleles increased and the 499T-939C haplotype had a significantly increased risk of idiopathic azoospermia (OR = 7.97; 95% CI = 3.51–18.07) compared with other haplotypes. The results suggest that XPC Ala499Val (C>T) polymorphism is correlated with high risk of idiopathic azoospermia in the Han-Chinese population.     

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.     

A single-nucleotide polymorphism in the XPG gene, and tumour stage, grade, and clinical course in patients with nonmuscle-invasive neoplasms of the urinary bladder

OBJECTIVE: To evaluate whether the single nucleotide polymorphism (SNP), Asp1104His (G3507C), in the XPG gene affects malignant phenotypes of nonmuscle-invasive urinary bladder neoplasms (NIBN), by investigating associations between the SNP and clinicopathological variables in patients with NIBN. PATIENTS AND METHODS: The 233 patients constituted newly diagnosed cases of primary NIBN in the Stockholm area. The Asp1104His polymorphism in the XPG gene was genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The GC + CC genotypes were more frequent in stage pT1 tumours at initial diagnosis than pTa (odds ratio 1.9, 95% confidence interval 1.0-3.5, P = 0.048). The difference was larger in the young group (4.6, 1.9-11.8, P = 0.001). In the young group, the GC + CC genotypes were significantly more frequent in high-grade than in low-grade tumours (3.1, 1.5-6.8, P = 0.004) whereas in the older group the genotypes were less frequent in high-grade tumours (0.3, 0.1-0.7, P = 0.007). The XPG genotypes were not associated with tumour recurrence, stage progression or survival. CONCLUSION: These results suggest that the SNP in the XPG gene might be related to tumour invasiveness in NIBN.     

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 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.