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。     

XRCC1单核苷酸多态性与含铂类药物化疗对肝肾功能影响相关性分析

目的探讨X射线损伤修复交叉互补基因1单核苷酸（XRCC1）多态性与恶性肿瘤患者铂类药物化疗前后肝肾功能变化的关系。方法化疗前采集外周静脉血,采用多聚酶链反应一高温连接酶反应（PCR—LDR）,进行XRCC1 Arg399Gln基因多态性的分型,观察化疗前后患者胆红素、转氨酶、蛋白、GGT、碱性磷酸酶、尿素氮、肌酐、尿酸等多项指标改变情况。结果携带XRCC1 399 Gln/Gln基因型患者,含铂类药物化疗前后总蛋白量的改变幅度低于XRCC1 399 Arg/Gln和XRCC1 399 Arg/Arg者;携带XRCC1 399 Arg/Gln基因型患者,含铂类药物化疗前后尿酸的变化高于XRCC1 399 Gln/Gln和XRCC1 399 Arg/Arg者;含铂类药物化疗前后其余各项肝肾功能指标的变化与XRCC1 Arg 399Gln单核苷酸多态性无关。结论 XRCC1单核苷酸多态性与含铂类药物化疗前后肝肾功能的改变无明显相关性。     

XRCC1单核苷酸多态性预测晚期NSCLC铂类药物化疗的敏感性

目的研究XRCC1单核苷酸多态性与晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)对以顺铂(cisplatin,DDP)或卡铂(carboplatin,CBP)为基础药物的化疗敏感性的关系。方法经病理学确诊的晚期NSCLC患者97例,采用DDP或CBP为基础药物的方案化疗,3个周期后进行疗效评价。以聚合酶链反应(PCR)结合限制性片段长度多态性(RFLP)检测XRCC1Arg194Trp和Arg399Gln基因型,并比较基因型与化疗敏感性的关系。结果(1)携带XRCC1194Arg/Trp的患者有效率高于携带Arg/Arg、Trp/Trp基因型的患者(P<0.05);携带至少一个Trp等位基因基因型患者的化疗敏感性是携带Arg/Arg基因型的3.4倍(OR=3.39,95%,CI=1.32~8.70,P<0.05)。(2)携带XRCC1399Arg/Arg、Arg/Gln、Gln/Gln基因型患者的有效率分别为36.4%、22.9%、28.6%,差异无统计学意义(P>0.05)。尚未发现XRCC1Arg194Trp和Arg399Gln基因多态性存在联合作用。结论XRCC1Arg194Trp单核苷酸多态性可能与晚期NSCLC对铂类药物的化疗敏感性相关。     

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.     

DNA修复基因XRCC1单核苷酸多态性与铂类药物化疗对外周血白细胞的影响相关性分析

目的 探讨X射线损伤修复交叉互补基因1单核苷酸多态性与应用铂类药物化疗前后外周血白细胞变化的关系.方法 化疗前采集外周静脉血,用多聚酶链反应-高温连接酶反应(PCR-LDR)进行XRCC1 Arg399Gln基因多态性的分型;观察化疗前后白细胞计数改变的情况.结果 XRCC1 Arg399Gln各基因型与化疗后白细胞总数、中性粒细胞计数下降无相关性(P＞0.05);携带XRCC1 399Arg/Gln及Gln/Gln基因型的患者化疗后淋巴细胞计数低于Arg/Arg者,而淋巴细胞下降的相对数要高于Arg/Arg者,化疗淋巴细胞下降绝对值无显著性差异.结论 XRCC1 399Arg/Gln基因型与化疗后淋巴细胞下降相关,在一定程度上可以预测化疗后淋巴细胞减少的程度.     

DNA修复酶XRCC1基因多态与非小细胞肺癌对GP方案化疗的敏感性

目的 研究DNA修复酶XRCC1基因Codon 194和Codon 399多态与非小细胞肺癌（NSCLC）患者对吉西他滨/顺铂（GP）方案化疗敏感性的关系.方法 收集经病理学确诊的NSCLC 57例,所有病例化疗前抽静脉血,提取白细胞DNA,用PCR-RFLP技术检测XRCC1 194和399基因型.所有患者均经PDD/GEM化疗方案治疗.结果 ①NSCLC患者中,XRCC1 194 Arg/Arg、 Arg/Trp 、Trp/Trp基因型者分别为30例（52.6%）、23例（40.4%）和4例（7.0%）;XRCC1 399 Arg/Arg、 Arg/Gln、Gln/Gln基因型者分别为31例（54.4%）、23例（40.3%）和3例（5.3%）.经化疗后,19例患者有效,总有效率33.3%.②XRCC1 194 Trp/Trp、Tp/Arg和Arg/Arg基因型者的化疗有效率分别为50.0%、52.2%和16.7%.携带Trp等位基因者的化疗有效率（51.9%）显著高于Arg/Arg基因型者（χ^2=6.41,P=0.0113）;XRCC1 399 Arg/Arg、Arg/Gln和Gln/Gln基因型者的化疗有效率分别为35.5%、34.8%和0,各组间的差异无显著性.XRCC1 194与XRCC1 399多态之间在化疗敏感性方面存在明显的交互作用,同时携带194 Arg/Arg和399 Arg/Arg基因型者的化疗有效率仅为7.7%（1/13）,而同时携带XRCC1 194 Trp等位基因和399 Arg/Arg基因型者的化疗有效率为58.8%（10/17）,2组之间差异显著（Fisher＇s双侧检验：P=0.0067）.结论 DNA修复酶基因XRCC1多态与NSCLC对GP方案化疗的敏感性有关,患者的基因型检测有可能作为预测NSCLC 对GP方案化疗敏感性的指标.     

XRCC1 单核苷酸多态性预测晚期NSCLC铂类药物化疗的敏感性

 目的 研究XRCC1单核苷酸多态性与晚期非小细胞肺癌（nowsmallcelllungcancer，NSCLC）对以顺铂（cisplatin，DDP）或卡铂（carDoplatin，CBP）为基础药物的化疗敏感性的关系。方法 经病理学确诊的晚期NSCLC患者97例，采用DDP或CBP为基础药物的方案化疗，3个周期后进行疗效评价。以聚合酶链反应（PCR）结合限制性片段长度多态性（RFLP）检测RiCelArg194Trp和Arg399G1n基因型，并比较基因型与化疗敏感性的关系。结果 （1）携带RiCel194Arg／Trp的患者有效率高于携带Arg／Arg、Trp／Trp基因型的患者（P〈0．05）；携带至少一个Trp等位基因基因型患者的化疗敏感性是携带Arg／Arg基因型的3．4倍（OR=3．39，95％，CI=1．3248．70，P〈0.05）。（2）携带RiCel399Arg／Arg、Arg／G1n、Gin／Gin基因型患者的有效率分别为36．4％、22．9％、28．6％，差异无统计学意义（P〉0.05）。尚未发现RiCelArg194Trp和Arg399Gln基因多态性存在联合作用。结论 XRCClArg194Trp单核苷酸多态性可能与晚期NSCLC对铂类药物的化疗敏感性相关。     

DNA修复基因多态性与肺癌顺铂化疗敏感性的研究

目的:研究切除修复交叉互补基因1(excision repair cross-complementing gene 1,ERCC1)Asn118Asn、切除修复交叉互补基因2(excision repair cross-complementing gene 2,ERCC2)Lys751Gln和X线修复交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)Arg399Gln单核苷酸多态性与非小细胞肺癌(non-small cell lung cancer,NSCLC)对铂类药物化疗敏感性的相关性。方法:采用基因测序的方法,检测89例以铂类药物为主要化疗方案的NSCLC患者外周血DNA中ERCC1基因Asn118Asn、ERCC2基因Lys751Gln和XRCC1基因Arg399Gln的基因型;采用统计学方法分析不同基因型与化疗疗效的相关性。结果:89例NSCLC患者采用铂类药物化疗总有效率为29.2%;ERCC1基因Asn118Asn和ERCC2基因Lys751Gln基因型在化疗有效组和无效组之间的分布,差异无统计学意义(P>0.05);而携带XRCC1基因Arg399Arg与携带至少1个Gln等位基因(Arg399Gln和Gln399Gln)基因型患者的有效率分别为76.9%和23.1%(χ2=11.1,P=0.001)。携带XRCC1基因Arg399Arg基因型患者对化疗的敏感性明显高于携带至少1个Gln等位基因型的患者(比值比为5.228,95%可信区间为1.776～15.387,P=0.003)。ERCC1、ERCC2和XRCC1基因型的联合可以提高化疗的有效率。结论:ERCC1、ERCC2和XRCC1基因的单核苷酸多态性的联合可能与NSCLC对铂类药物化疗敏感性具有相关性。     

DNA修复酶XRCC1基因多态性与晚期肺癌化疗敏感性的关系研究

目的:研究DNA修复酶XRCC1基因codon194和codon399多态性与肺癌患者对铂类药物为基础的化疗敏感性的关系。方法:收集经病理学确诊的晚期肺癌112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XRCC1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)在肺癌患者中,XRCC1194Are/Arg、Arg/Trp和Trp/Trp基因型者分别为48例(43·3%)、51例(45·9%)和12例(10·8%);XRCC1399Arg/Arg、Arg/Gln、Gln/Gln基因型者分别为65例(58·0%)、36例(32·1%)和11例(9·8%)。经化疗后,51例患者有效,总有效率45·5%。(2)XRCC1194Trp/Trp基因型者的有效率为75·0%,显著高于Arg/Arg基因型者(37·5%,χ2=5·36,P=0·0206))。前者的化疗敏感性是后者的5倍(95%CI:1·03~27·21)。同时拥有XRCC1194Trp/Trp和XRCC1399Arg/Arg基因型者的有效率为80·0%,显著高于其他基因型者(P=0·0417,OR=5·40,95%CI:0·98~38·90)。结论:XRCC1基因多态性与晚期肺癌对铂类药物为基础的化疗敏感性相关,检测XRCC1基因型可以预测晚期肺癌化疗的敏感性。     

XRCC1基因多态性与淋巴瘤发病风险的Meta分析

 目的运用Meta分析的方法综合评价DNA修复基因（X-ray repair cross-complementing group 1,XRCC1)的多 态性与淋巴瘤发病风险的关系。方法计算机检索PubMed、EMbase、中国期刊全文数据库、维普中文科技期刊数据库 、中国生物医学文献数据库,同时手工检索所有纳入文献的参考文献,收集截止到2010年2月关于XRCC1基因多态性 与淋巴瘤发病风险的病例对照研究,由两名研究者独立按照纳入标准筛选文献、提取资料并交叉核对,统计分析采 用RevMan5.0软件进行。结果共纳入11个病例对照研究,包括4 569例患者和5 746例对照。Meta分析结果显示： XRCC1 codon 399 基因型Gln/Gln、Arg/Gln和Gln/Gln+Arg/Gln与野生型Arg/Arg相比,频率差异均无统计学意义（ Gln/Gln vs. Arg/Arg:OR=1.04,95%CI［0.87,1.25］;Arg/Gln vs.Arg/Arg:OR=1.26,95%CI ［0.95,1.66］;Gln/Gln+Arg/Gln vs.Arg/Arg:OR=1.02,95%CI ［0.91,1.13］）,Gln/Gln+Arg/Gln基因型则有可 能增加霍奇金淋巴瘤的发病风险（OR=1.31,95%CI［1.02,1.69］）,XRCC1 codon280和XRCC1 codon 194的基因多 态性在患者和对照组之间的差异无统计学意义（XRCC1 codon280 His/His+Arg/His vs.Arg/Arg:OR=0.97,95%CI ［0.69,1.38］;XRCC1 codon 194 Trp/Trp+Arg/Trp vs.Arg/Arg:OR=1.01,95%CI［0.78,1.32］）。结论DNA修复 基因XRCC1的基因多态性与非霍奇金淋巴瘤发病风险没有相关性,codon399位点的Gln/Gln+Arg/Gln基因型则有可能 增加霍奇金淋巴瘤的发病风险。     

XRCC1 polymorphisms and risk of nasopharyngeal carcinoma: a meta-analysis

Objective: Previous studies on the association between X-ray repair cross-complementing protein 1 (XRCC1) polymorphisms and nasopharyngeal carcinoma (NPC) risk showed inconsistent results. The aim of this study was to evaluate the effects of XRCC1 variants on NPC risk. Methods: A meta-analysis was performed with all eligible studies covering a total of 1,341 cases and 1,425 controls for the Arg194Trp polymorphism, 1,260 cases and 1,207 controls for the Arg280His polymorphism, and 1,644 cases and 1,678 controls for the Arg399Gln polymorphism. Results: No associations was found between Arg194Trp and Arg280His polymorphisms with NPC risk under all contrast models (co-dominant, dominant, and recessive models). However a deleterious effect of the 399Gln genotype was observed under the co-dominant model (Gln/Gln versus Arg/Arg, OR = 1.30, 95% CI : 1.01-1.69, P = 0.04). Under the recessive model (Gln/Gln versus Arg/Arg+Arg/Gln), the P value was marginally significant (OR = 1.28, 95% CI : 1.00-1.65, P = 0.05). However, the effect of the 399Gln genotype on NPC became non-significant after excluding one study from the meta-analysis because of departure from Hardy-Weinberg equilibrium. Conclusions: No associations was found between Arg194Trp and Arg280His polymorphisms with NPC risk, whereas the Arg399Gln genotype was associated with increased risk.     

The association of XRCC1 gene single nucleotide polymorphisms with response to neoadjuvant chemotherapy in locally advanced cervical carcinoma

Background

Platinum-based neoadjuvant chemotherapy (NAC) is new therapeutic strategy for locally advanced cervical carcinoma, but the variables used to predict NAC response are still infrequently reported. The aim of our study was to investigate the association between XRCC1 gene single nucleotide polymorphisms (SNPs) and NAC response.

Methods

Seventy patients with locally advanced cervical carcinoma who underwent NAC were collected. SNPs of XRCC1 (at codon 194 and 399) and XRCC1 protein expression were detected. The association of XRCC1 gene SNPs and protein expression with NAC response were analyzed.

Results

Response to NAC was not statistically significant in three genotypes, Arg/Arg, Arg/Trp, Trp/Trp of XRCC1 at codon 194(X² = 1.243, P = 0.07), while responses were significantly different in genotypes Arg/Arg, Arg/Gln, Gln/Gln of XRCC1 at codon 399 (X² = 2.283, P = 0.020). The risk of failure to chemotherapy in the patients with a Gln allele(Arg/Gln+Gln/Gln) was significantly greater than that with Arg/Arg(OR = 3.254, 95%CI 1.708 ~ 14.951). The expression level of XRCC1 protein was significantly associated with response to NAC. Moreover, the genotype with the Gln allele(Arg/Gln+Gln/Gln) at codon 399, but not codon at 194, presented a significantly higher level of XRCC1 protein expression than that with Arg/Arg genotype (F = 2.699, p = 0.009).

Conclusion

SNP of XRCC1 gene at codon 399 influences the response of cervical carcinoma to platinum-based NAC. This is probably due to changes in expression of XRCC1 protein, affecting response to chemotherapy.     

Prediction Value of XRCC 1 Gene Polymorphism on the Survival of Ovarian Cancer Treated by Adjuvant Chemotherapy

Objective: We conducted a prospective study to test the association between three amino acid substitutionpolymorphismic variants of DNA repair genes, XRCC1 (Arg194Trp), XRCC1(Arg280His) and XRCC1(Arg399Gln), and clinical outcome of ovarian cancer patients undergoing adjuvant chemotherapy. Methods:195 patients with primary advanced ovarian cancer and treated by adjuvant chemotherapy were included in ourstudy. All were followed-up from Jan. 2007 to Jan. 2012. Genotyping of XRCC1 polymorphisms was conductedby TaqMan Gene Expression assays. Results: The XRCC1 194 Trp/Trp genotype conferred a significant riskof death from ovarian cancer when compared with Arg/Arg (HR=1.56, 95%CI=1.04-3.15). Similarly, thosecarrying the XRCC1 399 Gln/Gln genotype had a increased risk of death as compared to the XRCC1 399Arg/Arg genotype with an HR (95% CI) of 1.98 (1.09-3.93). Conclusion: This study is the first to provide evidencethat XRCC1 gene polymorphisms would well be useful as surrogate markers of clinical outcome in ovariancancer cases undergoing adjuvant chemotherapy.     

XRCC1 and XRCC3 polymorphisms and their role as effect modifiers of unsaturated fatty acids and antioxidant intake on colorectal adenomas risk.

Whereas animal and in vitro studies support a role of unsaturated fatty acids in colon carcinogenesis, the epidemiologic evidence is inconclusive. Using a large sigmoidoscopy-based case-control study (753 cases and 799 controls) in Los Angeles County, we investigated possible associations between single-nucleotide polymorphisms in the XRCC1 (codons 194 Arg/Trp and codon 399 Arg/Gln) and XRCC3 (codon 241 Thr/Met) genes and colorectal adenoma risk and their possible role as modifiers of the effect of monounsaturated fatty acid, the ratio of omega-6/omega-3 polyunsaturated fatty acids, and antioxidant intake. We found no evidence of associations between the XRCC1 codon 194 Arg/Trp or Trp/Trp genotypes and the XRCC3 codon 241 Thr/Met or Met/Met genotypes. Subjects with the XRCC1 Gln/Gln genotype were inversely associated with adenoma risk (odds ratio, 0.6; 95% confidence interval, 0.4-0.9; P = 0.01) when compared with subjects with Arg/Arg and Arg/Gln genotypes combined. We found no evidence of gene-dietary fat interactions for the XRCC3 codon 241 polymorphism. However, our data suggest an XRCC1-unsaturated fat interaction. High monounsaturated fatty acid intake was associated with adenoma risk only among subjects with the XRCC1 codon 194 Arg/Arg and codon 399 Gln/Gln combined genotypes (P for interaction = 0.018). High omega-6/omega-3 polyunsaturated fatty acid ratios were associated with adenoma risk among subjects with the XRCC1 codon 194 Arg/Arg and codon 399 Gln/Gln or the codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.026). These interactions were not modified by antioxidant intake. However, low antioxidant intake was associated with an inverse association only among subjects with the XRCC1 codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.022), which was independent of unsaturated fat intake. Our data suggest that the XRCC1 codon 194 and codon 399 single nucleotide polymorphisms may modify the effect of unsaturated fatty acid and antioxidant intake and that this XRCC1 effect modification may explain, in part, previously reported inconsistencies on the role of unsaturated fatty acids and adenoma risk.     

XRCC1单核苷酸多态与晚期非小细胞肺癌对铂类药物化疗敏感性的相关性

背景与目的DNA修复能力与肿瘤细胞对铂类药物的敏感性密切相关。本研究探讨DNA修复基因XRCC1单核苷酸多态性与非小细胞肺癌(non-smallcelllungcancer,NSCLC)患者对顺铂(cisplatin,DDP)或卡铂(carboplatin,CBP)为主的化疗方案敏感性的关系。方法经病理学确诊的晚期NSCLC患者105例,采用DDP或CBP为主的方案化疗,2～3个周期后进行临床疗效评价。以PCR-RFLP进行XRCC1Arg194Trp和Arg399Gln多态的基因分型,比较不同基因型对化疗敏感性的影响。比值比(OR)及其95%可信区间(CI)由logistic回归模型计算。结果携带至少一个Trp等位基因者化疗有效率为43.1%,显著高于携带Arg/Arg基因型的20.3%(OR=2.97,95%CI=1.15～7.72;P<0.05)。携带XRCC1399Arg/Arg基因型者化疗有效率为41.5%,显著高于携带至少一个Gln等位基因者的21.2%(OR=2.65,95%CI=1.03～6.87;P<0.05)。这两个多态之间存在联合作用,同时携带194Arg/Trp和399Arg/Arg基因型的患者,治疗有效率为66.7%,明显高于携带其它基因型的患者(有效率20.0%～23.1%)。结论XRCC1基因多态与NSCLC患者对铂类药物化疗的敏感性相关。     

DNA repair gene XRCC1 polymorphisms, smoking, and esophageal cancer risk

To investigate the effect of X-ray repair cross complementing 1 (XRCC1) genetic polymorphisms on esophageal cancer risk, we determined XRCC1 polymorphisms at codon 194 (Arg --> Trp) and codon 399 (Arg --> Gln) in 135 patients with esophageal squamous cell carcinoma (ESCC) and 152 normal controls from hospitals. Although polymorphism at codon 194 was not associated with risk for ESCC, we found that the frequency of XRCC1 399 Gln/Gln genotype in ESCC patients (14.1%) was significantly higher than that in normal controls (3.3%), and that XRCC1 399 Gln/Gln genotype was associated with an increased risk of ESCC (odds ratio (OR) = 5.15, 95% confidence interval (CI): 2.42-0.93). In addition, we found that the risk for smoker increased 4.2-fold than non-smokers in the 399 Gln/Gln genotype (OR = 4.20, 95% CI: 2.37-7.44). These results suggest that XRCC1 399 Gln/Gln genotype may contribute to the risk of ESCC and modify risk associated with smoking.     

Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to glioma

Background: The XRCC1 gene encodes the XRCC1 protein, which complexes with three other DNA repair enzymes involved in the base-excision repair (BER) pathways. Different XRCC1 polymorphisms may increase the risk of cancers by impairing interaction with other enzymatic proteins and consequently altering DNA repair activity, and result in carcinogenesis. Our study aimed to investigate any association between three polymorphisms of the XRCC1 gene at codon 194, 280 and 399 and potential glioma risk. Methods: We collected 127 patients with primary glioma and 249 controls who requested general health examinations from Union Hospital of Tongji Medical College hospital from March 2007 to September 2010. A total of 5 ml venous blood was drawn from each subject. The polymorphisms of XRCC1 gene at codons 194, 280 and 399 were analyzed based on duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method. Results: The homozygous Trp/Trp and heterozygotes Arg/Trp variants of codon 194 had a 2.12 fold and 1.46 fold increased risk of glioma compared to the homozygous Arg/Arg wide genotypes. The same effect was found in codon 399, the codon 399 Gln/Gln and Arg/Gln genotypes being associated with a 2.24 fold and 1.67 fold increased risk in glioma. When comparing the codon 194 Arg/Arg and 399 Arg/Arg genotypes, the combination of codon 194 Trp allele and 399 Gln allele had a heavy increase in glioma risk (OR=2.87, 95%CI=1.56-6.73). Conclusion: The present study provided evidence of a potential role for XRCC1 codon 194 and 399 polymorphisms in genetic predisposition to glioma among the Chinese population. This analysis of correlation of DNA repair genes and glioma may provide a deeper insight into the genetic and environment factors for cancer risk.     

Polymorphisms in the DNA repair gene XRCC1 and breast cancer.

X-ray repair cross complementing group 1 (XRCC1) encodes a protein involved in base excision repair. We examined the association of polymorphisms in XRCC1 (codon 194 Arg-->Trp and codon 399 Arg-->Gln) and breast cancer in the Carolina Breast Cancer Study, a population-based case-control study in North Carolina. No association was observed between XRCC1 codon 194 genotype and breast cancer, and odds ratios (ORs) were not modified by smoking or radiation exposure. A positive association for XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes compared with Arg/Arg was found among African Americans (253 cases, 266 controls; OR = 1.7, 95% confidence interval, 1.1-2.4) but not whites (386 cases, 381 controls; OR =1.0, 95% confidence interval, 0.8-1.4). Among African-American women, ORs for the duration of smoking were elevated among women with XRCC1 codon 399 Arg/Arg genotype (trend test; P < 0.001) but not Arg/Gln or Gln/Gln (P = 0.23). There was no difference in OR for smoking according to XRCC1 codon 399 genotype in white women. ORs for occupational exposure to ionizing radiation were stronger for African-American and white women with codon 399 Arg/Arg genotype. High-dose radiation to the chest was more strongly associated with breast cancer among white women with XRCC1 codon 399 Arg/Arg genotype. Our results suggest that XRRC1 codon 399 genotype may influence breast cancer risk, perhaps by modifying the effects of environmental exposures. However, interpretation of our results is limited by incomplete knowledge regarding the biological function of XRCC1 alleles.