广西扶绥县壮族人群 XRCC1 Arg399Gln（rs25487）和Arg280His（rs25489）多态性与肝癌家系遗传易感性的关系

目的:研究广西壮族自治区扶绥县壮族人群肝细胞癌(hepatocellular carcinoma,HCC)家系DNA修复基因XRCC1Arg399Gln(rs25487)和Arg280His(rs25489)多态性与HCC家系遗传易感性的相关性。方法:采用病例-对照研究和质谱检测方法,对广西扶绥县壮族人群20个HCC家系组79例和10个正常对照家系组40例进行XRCC1基因Arg399Gln(rs25487)和Arg280His(rs25489)基因型分布频率检测,应用非条件Logistic回归分析基因多态性与HCC发生危险性的关系,并将实验结果结合临床资料进行统计学分析。结果:正常对照家系组人群XRCC1 Arg399Gln(rs25487)中AG、AA基因型个体发生HCC的风险分别是GG基因型个体的9倍(95%CI=0.828~97.780,P=0.071)和5.14倍(95%CI=0.445~59.450,P=0.190);HCC家系组人群中非HCC患者AG、AA基因型的个体发生HCC的风险分别是GG基因型个体的4倍(95%CI=0.689~23.230,P=0.122)和2.85倍(95%CI=0.464~17.583,P=0.257),差异均无统计学意义。Arg280His(rs25489)正常家系组人群中GA基因型个体发生HCC的风险分别是GG基因型个体的2.4倍(95%CI=0.530~10.877,P=0.256);HCC家系组人群中非HCC患者GA基因型的个体发生HCC的风险分别是GG基因型个体的1.02倍(95%CI=0.286~3.650,P=0.973),差异均无统计学意义。结论:广西扶绥壮族人群中XRCC1 Arg399Gln(rs25487)和Arg280His(rs25489)多态性与患HCC的风险无显著相关性。     

中国人群XRCC1 Arg399Gln 基因多态性与结直肠癌易感性关系的Meta分析

摘 要：［目的］探讨X线修复交叉互补基因1（X-ray repair cross complementing group 1,XRCC1）Arg399Gln基因多态性与中国人群结直肠癌易感性的关系。［方法］在PubMed、MEDLINE、EMBASE、中国知网、维普、中国生物医学文献及万方数据库中检索建库至2016年4月10日之间发表的有关XRCC1 Arg399Gln基因多态性与中国人群结直肠癌易感性关系的相关文献。按照纳入和排除标准独立选择文献、提取资料,采用Stata 12.0软件进行Meta分析,计算合并比值比（OR）及其95%可信区间（95%CI）,并进行敏感性分析和发表偏倚的估计。［结果］ 共纳入11项研究,包括3502例患者和4828例对照者。Meta分析结果显示,在Gln/Gln vs Arg/Gln遗传模型中,XRCC1 Arg399Gln基因多态性与中国人群结直肠癌发生风险有显著相关性,与基因型Arg/Gln相比,基因型Gln/Gln增加了中国人群罹患结直肠癌的风险（OR=1.23,95%CI：1.04~1.46,P=0.016）。其余遗传模型中两者间无明显相关性。［结论］ 在Gln/Gln vs Arg/Gln遗传模型中,XRCC1 Arg399Gln基因多态性与中国人群结直肠癌易感性相关,基因型Gln/Gln增加中国人群罹患结直肠癌的风险。     

食管癌中ERCC2/XPD和XRCC1基因多态性的表达

目的:探讨DNA损伤修复基因ERCC2/XPD和XRCC1基因多态性与食管癌遗传易感性的关系。方法:采用病例对照研究设计,选取100例食管癌病例和80例正常对照。选取ERCC2/XPD Lys751Gln和XRCC1 Arg399Gln基因多态性为研究位点,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行多态性检测,应用Logistic回归计算OR值及95%CI,比较不同基因型与食管癌发病风险的关系。结果:病例组和对照组中变异型等位基因ERCC2/XPD Lys751Gln的频率分别是15.7%和13.0%。与野生基因型Lys/Lys相比,携带XPD Lys/Gln和Gln/Gln基因型者患食管癌的危险度比值比(odds ratio,OR)分别是1.94(95%CI:1.22～3.36)和0.56（95%CI:0.15～2.64)。变异型等位基因XRCC1 399Gln的频率在病例组和对照组中分别是29.8%和30.2%,与野生基因型XRCC1 Arg/Arg相比,带Arg/Gln和Gln/Gln基因型者患食管癌的OR分别是0.94(95%CI:0.69～1.31)和1.83(95%CI:0.84～3.89)。分析结果提示饮酒、酸泡菜与XPD Lys751Gln基因多态存在交互作用,交互效应OR值分别为2.24(95%CI:1.18～2.87)和2.53(95%CI:1.71～3.46),携带XPD Lys751Gln和XRCC Arg1399Gln突变基因者若同时暴露于酸泡菜或酒精,则患食管癌的危险显著增加,相较未暴露于上述因素者,OR值均增大。结论:DNA损伤修复基因ERCC2/XPD和XRCC1单核苷酸多态性可能与当地居民食管癌遗传易感性有关,与饮酒、酸泡菜存在交互作用。     

XRCC1多态性与非吸烟女性肺腺癌易感性的关系

背景与目的XRCC1是一种DNA损伤修复基因，其单核苷酸多态性异常是导致DNA修复能力个体差异的重要原因，可能导致个体患肺癌的危险升高。本研究的目的是探讨XRCC1单核苷酸多态性与非吸烟女性肺腺癌易感性的关系。方法采用以医院患者为基础的病例对照研究方法，研究对象包括非吸烟女性肺腺癌患者126例和同期其它肺部疾病对照126例。以聚合酶链反应一限制性片段长度多态性方法分析XRCC1基因Arg399Gln多态性，比较不同基因型与非吸烟女性肺腺癌的关系，并探讨油烟暴露与基因多态交互作用对患癌风险的影响。结果与携带399Arg／Arg基因型者比较，携带399Gln／Gln基因型者患肺腺癌的风险是其8．695倍（95％CI为3．343～22．614）。携带等位基因399Gln又有油烟暴露的个体患肺腺癌的风险明显增高，校正的比值比为5．21（95％CI为1．85～14．70，P〈0．001）。结论XRCC1基因Arg399 Gln多态性可能是非吸烟女性肺腺癌的遗传易感因素。     

XRCC1 Arg399Gln位点多态性与乳腺癌易感性的Meta分析

[目的]评估X射线交叉互补修复基因1(X-ray repair cross complementing protein 1,XRCC1)基因Arg399Gln位点单核苷酸多态性与高加索及亚洲人群乳腺癌(breast cancer,BC)易感性的关系。[方法]检索Pub Med、Embase、中国期刊全文数据库(CNKI)、万方数据库、中国生物医学文献数据库(CBM)和中文科技期刊全文数据库(VIP)等数据库,获取有关XRCC1 Arg399Gln位点多态性与高加索及亚洲人群乳腺癌易感性关系的病例对照研究的资料,以病例组及对照组XRCC1 Arg 399Gln等位基因分布的比值比(OR)为效应指标,应用Meta分析软件Review Manager(version 5.0.10)对各研究原始数据进行统计处理及异质性检验,计算合并OR值及其95%可信区间。[结果 ]共纳入24项病例对照研究,包括15151例乳腺癌患者和17179例对照。Meta分析结果显示,XRCC1 Arg399Gln位点Gln/Gln突变型可能会增加亚洲人群乳腺癌的发病风险[Gln/Gln vs.Arg/Arg亚洲组:OR=1.20(95%CI:1.03~1.39),P=0.02;Gln/Gln vs.Arg/Arg+Arg/Gln亚洲组:OR=1.20(95%CI:1.04~1.38),P=0.01。Gln/Gln vs.Arg/Arg OR=1.01(95%CI:0.94~1.09),Z=0.35,POR=0.73;Gln/Gln+Arg/Gln vs.Arg/Arg OR=1.02(95%CI:0.95~1.09,Z=0.58,POR=0.56;Gln/Gln vs.Arg/Arg+Arg/Gln OR=1.01(95%CI:0.95~1.08),Z=0.33,POR=0.74)。[结论]XRCC1 Arg399Gln位点Gln/Gln突变型可能与亚洲人群乳腺癌易感性相关。     

XRCC1 Arg399Gln位点多态性和结直肠癌易感性关系的Meta分析

[目的]探讨X射线交叉互补修复基因1（X-ray repair cross-complementing group1,XRCC1）的399位点（Arg399Gln）多态性与结直肠癌（CRC）易感性的关系。[方法]检索中国生物医学数据库（CBM）、PubMed、Springer等数据库,获取有关XRCC1Arg399Gln多态性同结直肠癌易感性关系的病例对照研究并进行Meta分析,以病例组及对照组XRCC1Arg399Gln等位基因分布的比值比（OR）为效应指标,应用Meta分析软件Review Manager（version5.0.10）对各研究原始数据进行统计处理及异质性检验,计算合并OR值及其95%可信区间（95%CI）。[结果]纳入11项病例对照研究,共2287例结直肠癌患者和3485例对照,Meta分析结果显示,Gln/Gln vs.Arg/Arg OR=1.12,95%CI为0.76～1.65,Z=0.58,POR=0.56;Gln/Gln＋Arg/Gln vs.Arg/Arg OR=1.11,95%CI为0.85～1.44,Z=0.78,POR=0.43;Gln/Glnvs.Arg/Arg＋Arg/Gln OR=1.07,95%CI为0.79～1.46,Z=0.43,POR=0.67;Arg/Gln vs.Arg/Arg OR=1.14,95%CI为0.88～1.48,Z=1.02,POR=0.31。[结论]XRCC1Arg399Gln多态性与结直肠癌易感性之间无显著相关性。     

X射线损伤修复交叉互补基因1多态性与非吸烟女性肺癌易感性的关系

目的探讨X射线损伤修复交叉互补基因1（XRCCl）单核苷酸多态性与非吸烟女性肺癌易感性的关系。方法采用以医院患者为基础的病例一对照研究方法,非吸烟女性肺癌患者50例,非癌对照50例。以聚合酶链反应一限制性片段长度多态性（PCR—RFLP）方法检测XRCC1基因Arg399Gln多态性,计算各基因型的比值比（OR）,并探讨烹饪油烟暴露史与多态基因型交互作用对肺癌患癌风险的影响。结果肺癌组与对照组XRCC1 Arg399Gln多态基因型分布差异无统计学意义（P〉0．05）,而腺癌组基因型分布与对照组差异有统计学意义（P〈0．05）。相对于399Arg／Arg基因型,携带至少1个Gin等位基因的个体患肺腺癌的调整OR值为2．19（95％CI为0．73～6．61）,而XRCC1 399Gin／Gin基因型携带者的调整OR值为14．12（95％CI为2、14～92．95）。携带至少1个399Gln等位基因的烹饪油烟暴露者患肺腺癌的风险明显升高,调整OR值为6．29（95％c,为1．99～19、85）。结论XRCC1基因Arg399Gln多态可能是非吸烟女性肺腺癌的遗传易感因素,399Gln等位基因与烹饪油烟交互作用,可提高非吸烟女性肺腺癌的发病风险。     

广西扶绥县人群DDX39基因单核苷酸多态性与肝癌家系遗传易感性的关系

目的 探讨广西扶绥县原发性肝细胞癌(hepatocellular carcinoma,HCC,以下简称“肝癌”)高发家系人群DDX39基因rs12461754位点单核苷酸多态性与肝癌遗传易感性的相关性。方法 选取广西扶绥县20个肝癌高发家系共77例和10个正常对照家系共35名为研究对象,采用基质辅助激光解析电离飞行时间质谱技术(matrix assisted laser desorption ionization-time of fight-mass, MALDI-TOF-MS)检测DDX39基因rs12461754位点在两组中的基因型和等位基因频率。结果 正常对照家系组人群DDX39 基因rs12461754 位点携带A等位基因型的个体发生肝癌的风险是G等位基因型个体的0.407倍(95%CI:0.125~1.326,P=0.136);在肝癌高发家系非肝癌组人群中,携带A等位基因型的个体发生肝癌的风险是G等位基因型个体的0.981倍(95%CI:0.298~3.326,P=0.976); DDX39基因rs12461754位点GG、AG、AA基因型在肝癌高发家系肝癌组、肝癌高发家系非肝癌组及正常对照家系组三组间相互比较,差异无统计学意义(P>0.05)。结论 DDX39基因rs12461754位点单核苷酸多态性与广西扶绥县肝癌家系遗传易感性无明显相关性。     

XRCC1和XRCC3单核苷酸多态性与晚期非小细胞肺癌铂类药物化疗疗效的相关性

背景与目的 DNA修复基因多态性预测铂类药物化疗敏感性对非小细胞肺癌(non-small cell lung cancer,NSCLC)个体化治疗具有重要意义.本研究旨在探讨X线修复交错互补基因1(X-ray repair cross complementing gene 1,XRCC1)和X线修复交错互补基因3(X-ray repair cross complementing gene 3,XRCC3)单核苷酸多态性与晚期NSCLC患者对铂类药物化疗疗效的关系.方法 采用PCR-RFLP方法检测130例以含铂方案化疗的晚期NSCLC患者外周血DNA中XRCC1 Arg194 Trp、Arg399 Gln和XRCC3 Thr241 Met基因多态性,分析其基因型与化疗疗效的关系.结果 130例晚期NSCLC患者采用含铂方案化疗2个周期后,化疗总有效率为33.8％.XRCC1 194和399基因多态性与铂类药物化疗敏感性相关,而XRCC3 241基因多态性与化疗敏感性无关(P=0.145).携带至少1个XRCC1 194 Trp等位基因者化疗有效率至少是携带Arg/Arg基因型患者的2.5倍(42.1％vs22.2％,OR=2.545,95％CI:1.159-5.590,P=0.020).携带XRCC1399 Arg/Arg基因型者的化疗有效率为45.5％,明显高于携带至少1个Gln等位基因者(21.9％)(OR=0.336,95％CI:0.156-0.722,P=0.005).XRCC1 194和399基因多态性之间存在联合作用,同时携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg基因型者的化疗有效率明显高于同时携带194 Arg/Arg和399 Arg/Gln基因型者(44.4％ vs 18.8％,OR=3.467,95％CI:1.223-9.782,P=0.019).XRCC1和XRCC3基因多态性在化疗敏感性方面存在一定的联合作用,携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg野生型基因同时又携带XRCC3 241 Thr/Met基因型者的化疗有效率明显高于其它基因型携带者.结论 XRCC1和XRCC3的多态联合可能与晚期NSCLC患者对铂类药物化疗疗效具有相关性.     

GHR基因单核苷酸多态性与广西肝癌家系遗传易感性的研究

目的 探讨生长激素受体（growth hormone receptor,GHR）基因单核苷酸多态性（single nucleotide polymorphism,SNP）与广西扶绥县肝癌家系遗传易感性的关系。方法 选取广西扶绥县25个肝癌家系和17个健康对照家系人群为研究对象,其中肝癌家系肝癌患者25例（肝癌家系肝癌组）、非肝癌者81名（肝癌家系非肝癌组）;健康对照家系80名（对照组）。采用飞行时间质谱技术检测GHR基因rs6451620位点基因型及等位基因分布频率,非条件logistic回归模型分析rs6451620位点多态性与肝癌遗传易感性的关系。结果 GHR基因rs6451620位点存在G和A两种等位基因,AA、GA、GG 3种基因型。GHR基因rs6451620位点基因型频率符合遗传平衡。GHR基因rs6451620位点等位基因G和A在肝癌家系肝癌组中的分布频率分别为64%和36%,肝癌家系非肝癌组为60.5%和39.5%,对照组为70.6%和29.4%。以肝癌家系肝癌组和非肝癌组人群为研究对象时,携带A等位基因型的个体发生肝癌的风险是G等位基因型个体的0.81倍（95%CI：0.27～2.41,P=0.699）,以肝癌家系肝癌组和健康对照人群为研究对象时,携带A等位基因型个体发生肝癌的风险是G等位基因型个体的1.49倍（95%CI：0.73～3.04,P=0.274）。结论 GHR基因rs6451620位点单核苷酸多态性与广西肝癌家系遗传易感性无明显相关性。     

Evaluation of DNA repair gene XRCC1 polymorphism in prediction and prognosis of hepatocellular carcinoma risk

We conducted a case-control study in China to clarify the association between XRCC1-Arg399Gln polymorphism and HCC risk. A total of 150 cases and 158 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method. All analyses were performed using the STATA statistical package. A significantly increased risk was associated with the Arg/Gln genotype (adjusted OR 1.78, 95%CI=1.13-2.79) compared with genotype Arg/Arg. In contrast, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.69 (0.93-2.66). A significant association was found between positive HBsAg and Arg/Gln, with an OR of 3.43 (95% CI=1.45-8.13). Patients carrying Gln/Gln genotypes showed significantly lower median survival than Arg/Arg genotypes (HR=1.38, 95% CI=1.04-1.84). Further Kaplan-Meier analysis showed decreased median survival in Arg/Gln+Gln/Gln genotype carriers in comparison to Arg/Arg carriers (HR=1.33, 95% CI=1.02-1.76). In conclusion, we observed that XRCC1-Arg399Cln polymorphism is associated with susceptibility to HCC, and XRCC1 Gln allele genotype showed significant prognostic associations.     

An Updated Meta-analysis on the Association of X-Ray Repair Cross Complementing Group 1 Codon 399 Polymorphism with Hepatocellular Carcinoma Risk

Background: A number of studies have reported the association of X-ray repair cross-complementing group1 (XRCC1) Arg399Gln polymorphism with susceptibility to hepatocellular carcinoma (HCC). However, theresults were inconsistent and inconclusive. The aim of this study was to comprehensively explore the associationof XRCC1 Arg399Gln variant with HCC risk. Materials and Methods: Systematic searches of PubMed, Elsevier,Science Direct, CNKI and Chinese Biomedical Literature Database were performed. Pooled odds ratio (OR)with 95% confidence intervals (CI) was calculated to estimate the strength of association. Results: Overall,we observed an increased HCC risk among subjects carrying XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln genotypes (OR=1.20, 95%CI: 1.05-1.38, OR=1.16, 95%CI: 1.05-1.28, and OR=1.14, 95%CI:1.04-1.24, respectively) based on 20 studies including 3374 cases and 4633 controls. In subgroup analysis, weobserved an increased risk of XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln polymorphisms forHCC in hospital-based study (OR=1.25, 95%CI: 1.03-1.51, OR=1.21, 95%CI: 1.07-1.36 and OR=1.18, 95%CI:1.06-1.31, respectively) and in Asian population (OR=1.19, 95%CI: 1.03-1.38, OR=1.17, 95%CI: 1.04-1.30 andOR=1.14, 95%CI: 1.04-1.25, respectively). Limiting the analysis to the studies with controls in agreement withHardy-Weinberg equilibrium (HWE), we observed an increased HCC risk among Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln genotype carriers (OR=1.17, 95%CI: 1.05-1.29, OR=1.12, 95%CI: 1.00-1.25 and OR=1.11, 95%CI:1.02-1.21, respectively). Conclusions: This updated meta-analysis results suggest that XRCC1 Arg399Gln variantsmay contribute to HCC risk. Well-designed studies with larger sample size were required to further verify ourfindings.     

XRCC1基因多态性与卵巢癌对铂类药物化疗敏感性的相关性研究

目的 探讨X线修复交叉互补基因1（XRCC1）Arg194Trp和Arg399Gln位点多态性与卵巢癌对铂类药物化疗敏感性之间的关系。方法 选取82例首次术后以铂类为基础化疗达6个周期的卵巢癌患者,采用聚合酶链反应 限制性片段长度多态性分析（PCR RFLP）检测外周血XRCC1 Arg194Trp和Arg399Gln位点的基因型,分别比较两个位点的不同基因型与化疗敏感性及两个位点之间的关系。结果 XRCC1 Arg194Trp存在3个基因型,即Arg／Arg、Arg／Trp、Trp／Trp,基因分布频率分别为47.6％、43.9％、8.5％;XRCC1 Arg399Gln亦存在3个基因型,即Arg／Arg、Arg／Gln、Gln／Gln,基因分布频率分别为25.6％、40.2％、34.1％。XRCC1 Arg399Gln 的不同基因型在FIGO分期和年龄分组中的差异均有统计学意义（P＜0.05）。化疗敏感组与不敏感组两个位点多态性基因型之间的差异均有统计学意义（P＜0.05）。XRCC1 Arg194Trp的Trp／Trp和Arg 399Gln的Gln/Gln基因型比Arg／Arg基因型更易对铂类药物产生耐药性,比值比分别增加至13.50倍（95％CI：1.461～124.739）和7.65倍（95％CI：2.012～29.088）。同时携带Arg194Trp Arg／Trp和Arg399Gln Gln／Gln基因型的患者对化疗不敏感率高达84.62％（OR=22.00,95％CI：2.534～190.998;P＜0.05）。结论 XRCC1 Arg194Trp和Arg399Gln位点基因多态性与卵巢癌对铂类药物的化疗敏感性相关,并且两位点之间存在联合效应。     

An updated meta-analysis between the association of XRCC1 Arg399Gln polymorphism and hepatocellular carcinoma risk

Background: Various studies have evaluated the relationship between X-ray repair cross-complementinggroup 1 (XRCC1) Arg399Gln polymorphism and hepatocellular carcinoma (HCC) risk, but the conclusionshave been inconsistent and underpowered. The purpose of this updated meta-analysis was to examine whetherXRCC1 Arg399Gln polymorphism confers susceptibility to HCC. Methods: Eligible studies extracted fromPubMed, Embase, Cochrane Library, VIP (chinese) and CNKI (chinese) up to November 2013 were included inthe study. Pooled odds ratio (OR) together with their 95% confidence interval (CI) were estimated to evaluateXRCC1 Arg399Gln polymorphism and HCC risk. Results: Finally, 21 studies with 4,170 cases and 5,030controls were involved in our meta-analysis. The results demonstrated that there was significant associationbetween Arg399Gln polymorphism and HCC risk under two contrast models in overall populations (AG vs GG:OR=1.265, 95%CI=1.036-1.545, p=0.021; AA+AG vs GG: OR=1.240, 95%CI=1.021-1.506, p=0.030). In subgroupanalyses, significant association was found in Asians (A vs G: OR=1.175, 95%CI=1.013-1.362, p=0.033; AG vsGG: OR=1.317, 95%CI=1.070-1.622, p=0.009; AA+AG vs GG: OR=1.289, 95%CI=1.055-1.575, p=0.013) andCaucasians (A vs G: OR=0.591, 95%CI=0.361-0.966, p=0.036; AA+AG vs GG: OR=0.468, 95%CI=0.234-0.934,p=0.031). Conclusions: The results suggest that XRCC1 Arg399Gln polymorphism may increase HCC riskespecially among Asians. However, XRCC1 Arg399Gln polymorphism might act as a protective role againstHCC among Caucasians.     

Association of XPD and XRCC1 Genetic Polymorphisms with Hepatocellular Carcinoma Risk

Aim: XRCC1 and XPD are two major repair genes involved in nucleotide excision repair (NER), whichis reported to be associated with risk of several cancers. We explored the association of XRCC1 and XPDpolymorphisms with the risk of HCC. Methods: A total of 410 cases with HCC and 410 health controls werecollected. XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn genotyping wasperformed by duplex polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method.Results: XRCC1 194Trp/Trp was strongly significantly associated with an increased risk of HCC cancer whencompared with the wide-type genotype (OR=2.26, 95% CI=(1.23-5.38). Individuals carrying the XRCC1 399Gln/Gln showed increased risk of HCC (OR=1.74, 95%CI=1.06-2.74). The XPD 751Gln/Gln and Gln allele genotypewere associated with strong elevated susceptibility to HCC (OR=3.51 and 1.42, respectively). Conclusion: Theseresults suggest that polymorphisms in XRCC1 and XPD may have functional significance in risk of HCC.     

XRCCl和MGMT基因多态性与东北地区汉族人群胶质瘤易感相关性研究

目的：研究XRCCl和MGMT基因多态性与东北地区汉族人群胶质瘤易感性的关系。方法：采用病例一对照研究方法,收集东北地区汉族人群胶质瘤患者,同时随机选取同性别、民族、年龄相差±5岁、同期住院的非肿瘤门诊患者作为对照。其中XRCClArg399GIn多态性,采集366例胶质瘤患者和377例对照;MGMTLeu84Phe多态性,采集543例胶质瘤患者和495例对照;MGMT11e143Val多态性,采集369例胶质瘤患者和441例对照。采用PCR-RFLP方法分析XRCCl基因Arg399Gln位点和MGMT基因Leu84Phe、Ilel43Val位点的多态性,比较不同基因型与胶质瘤易感性的关系。结果：胶质瘤组中XRCCl399Gln等位基因频率为0．35,明显高于对照组0．27,差异有统计学意义．）x2=7．485,P=0．006。与Arg／Arg基因型比较,携带基因型Arg／Gln的个体胶质瘤患病风险增加,OR=1．36,95％CI为1．01～1．85,P=0．045;携带Gin／Gin的个体胶质瘤患病风险增加,OR=1．83,95％CI为1．10～3．05,p=0．019;携带Arg／Gln＋GIn／GIn的个体胶质瘤患病风险增加,0R=1．44,95％CI为1．08～1．93,p=0．013;携带等位基因Gln的个体胶质瘤患病风险增加,OR=l.36,95％cI为1．09～1．69,p=0．006。胶质瘤组中MGMT84Phe等位基因频率为0．16,明显高于对照组0．10,差异有统计学意义,x2=20．253,P〈0．001。与Leu／Leu基因型比较,携带基因型Leu／Phe的个体胶质瘤患病风险增加,OR＝1．61,95％cI为1．18～2．19,p=0．002;携带Phe／Phe的个体胶质瘤患病风险增加,OR=4．16,95％CI为1．68～10．30,p=0．001;携带Leu／Phe＋Phe／Phe的个体胶质瘤患病风险增加,0R=1．78,95％CI为1．33～2．39,Pd0．001;携带等位基因Phe的个体胶质瘤患病风险增加,OR=1．83,95％CI为1．40～2．38,P〈O．001。胶质瘤组中MGMT143Val等位基因频率为0．11,高于对照组0．10,但差异无统计学意义,x2=0．242,p=0．623。与Ile／Ile基因型比较,携带基因型Ile／Val或Val／Val或Ile／Val＋Val／Val以及等位基因Val的个体胶质瘤患病风险未增加,P〉0．05。结论：XRCClArg399Gln和MGMTLeu84Phe基因多态性可增加东北地区汉族人群患胶质瘤的风险,MGMT基因Ilel43Val位点基因多态性与胶质瘤易感性无关。     

Updated Assessment of the Association of the XRCC1 Arg399Gln Polymorphism with Lung Cancer Risk in the Chinese Population

Background: Published studies have reported relationships between X-ray repair cross-complementing group1 (XRCC1) Arg399Gln polymorphism and lung cancer risk in Chinese population. However, the epidemiologicalresults remained controversial. The objective of this study was to clarify the association of XRCC1 Arg399Glnpolymorphism with lung cancer risk in the Chinese population. Materials and Methods: Systematic searches wereperformed through the database of Medline/Pubmed, Web of Science, Embase, CNKI and WanFang MedicalOnline. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated to estimate the strength ofthe association. Results: Overall, we observed an increased lung cancer risk among subjects carrying XRCC1codon 399 Gln/Gln genotype (OR=1.36, 95%CI: 1.09-1.71) in the Chinese population on the basis of 19 studieswith 5,416 cases and 5,782 controls. We did not observe any association between XRCC1 codon 399 Arg/Gln andArg/Gln+Gln/Gln polymorphisms and lung cancer risk (OR=1.00, 95%CI: 0.92-1.08 and OR=1.05, 95%CI: 0.97-1.13, respectively). Limiting the analysis to studies with controls in agreement with Hardy-Weinberg equilibrium(HWE), we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype(OR=1.18, 95%CI: 1.01-1.38). When stratified by source of control, we observed an increased lung cancer riskamong subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-basedcontrols (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype onthe basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43). Conclusions: Our findings indicatedthat certain XRCC1 Arg399Gln variants might affect the susceptibility of lung cancer in Chinese population.Larger sample size studies are required to confirm our findings.     

Polymorphisms of DNA repair gene XRCC1 and hepatocellular carcinoma risk among East Asians: a meta-analysis

Association studies on the X-ray repair cross-complementing group 1 (XRCC1) polymorphisms (Arg194Trp, Arg280His, and Arg399Gln) in hepatocellular carcinoma (HCC) have shown conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Published literatures from PubMed, Embase, CNKI, and Chinese Biomedicine Database were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. Thirteen studies including 3,011 HCC cases and 3,619 controls were included in the meta-analysis of the association between XRCC1 Arg399Gln polymorphism and HCC risk. The results indicated that Arg399Gln polymorphism was significantly associated with risk of HCC in a codominant model (Gln/Gln vs. Arg/Arg, OR?=?1.32, 95 % CI?=?1.08–1.61; Arg/Gln vs. Arg/Arg, OR?=?1.41, 95 % CI?=?1.12–1.80) and a dominant model (Gln/Gln?+?Arg/Gln vs. Arg/Arg, OR?=?1.39, 95 % CI?=?1.15–1.69), but not in a recessive model (Gln/Gln vs. Arg/Gln?+?Arg/Arg, OR?=?1.13, 95 % CI?=?0.95–1.35). Limiting the analysis to the studies within Hardy–Weinberg equilibrium, the results were persistent and robust. When stratifying for region and source of controls, persistent results were observed in any subgroup. No evidence of association of Arg194Trp (980 HCC cases and 966 controls) and Arg280His (1,200 HCC cases and 1,236 controls) with HCC risk was found. No publication bias was found in the present study. The results from the present meta-analysis indicated that the Arg399Gln polymorphisms of XRCC1 may be a genetic susceptibility for HCC in the East Asian population. Further, large and well-designed studies are needed to confirm this conclusion.     

XRCC1 Arg399Gln基因多态性与中国人群肝细胞癌易感性的Meta分析

目的 探讨XRCC1 Arg399Gln基因多态性与肝细胞癌（HCC）易感性的关系。方法 计算机检索PubMed、中国生物医学文献（CBM）、中国知网、万方及维普等数据库,收集有关XRCC1 Arg399Gln基因多态性与HCC易感性关系的病例对照研究,提取纳入文献的相关数据进行Meta分析,以病例组与对照组XRCC1 Arg399Gln各种基因模型的比值比（OR）为效应指标,发表偏倚采用Eggers检验和Beggs检验。结果 共17篇文献符合纳入标准,累计病例数3301例,对照组4156例。XRCC1 Arg399Gln基因多态性与中国人群HCC易感性有明显关联性（G/G vs. A/A：OR=1.32,95％CI：1.13～1.54,P=0.000;A/G vs. A/A：OR=1.25,95％CI：1.10～1.41,P=0.000;A/G+G/G vs. A／A：OR=1.22,95％CI：1.09～1.36,P=0000;G／G vs. A／A+A／G：OR=1.20,95％CI：1.04～1.39,P=0.014）。根据健康对照组来源不同的亚组分析中,所有地区或者控制人口来源医院的研究结果均显示,XRCC1 Arg399Gln 基因多态性与HCC易感性有明显关联性,但控制人口非医院来源的研究结果显示XRCC1 Arg399Gln 基因多态性与HCC易感性无明显关联性;根据地区不同分组的亚组分析中,在广西地区,除隐性遗传模型外（G/G vs. A/A+A/G：OR=1.25,95％CI：0.95～1.65,P=0.115）,其余遗传模型结果显示XRCC1 Arg399Gln基因多态性与广西地区HCC易感性有明显相关性（G/G vs. A/A：OR=1.47,95％CI：1.10～1.95,P=0.009;A/G vs. A/A：OR=1.35,95％CI：1.17～1.56,P=0.000;A/G+G/G vs.A／A：OR=133,95％CI：1.16～1.52,P=0.000）。结论 XRCC1 Arg399Gln 基因多态性可能增加中国人群HCC的易感性,尤其在广西地区。     

MS-920: DNA repair gene polymorphisms, diet and colorectal cancer risk in Taiwan

This hospital-based case-control study examined whether polymorphic DNA repair genes: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, play a role in the susceptibility to colorectal cancer. We genotyped these polymorphisms for 727 newly diagnosed colorectal adenocarcinoma cases and 736 age and sex matched healthy controls in Taiwan. Although the colorectal cancer risk was not significantly associated with these genes, the risk was significantly elevated in younger subjects (< or =60 years) with the XRCC1 399Arg/Arg genotype compared to those with XRCC1 399Gln allele (OR=1.46, 95% CI=1.06-2.99, P=0.02). The stratified analysis showed that XRCC3 interacted with meat consumption (P for interaction=0.02), but was limited to the low meat consumption (OR=2.34, 95% CI=1.28-4.29). Our results suggest that the XRCC1 Arg399Gln polymorphism may contribute to the risk of early-onset colorectal cancer and the XRCC3 Thr241Met polymorphism may modify the risk for meat-associated colorectal cancer.