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基因Arg399Gln多态性与中国人群神经胶质瘤易感性Meta分析

目的:探讨XRCC1基因Arg399Gln (G/A)多态性与中国人群神经胶质瘤易感性的关系.方法:计算机检索Pubmed、EMBASE、中国知网、万方期刊、维普等中英文数据库,检索2014年10月之前公开发表的相关文献,对符合标准的文献采用NOS量表评价文献质量,应用RevMan5.1软件进行Meta分析.结果:共纳入9篇与XRCC1基因Arg399Gln多态性与神经胶质瘤易感性相关的病例对照研究,包括7 131例患者,其中病例组3 428例,对照组3 703例,NOS评分≥6分为高质量文献,仅2项研究质量评分＜6.Meta分析结果显示携带A等位基因可增加中国人群神经胶质瘤的患病风险(OR=1.20,95％CI:1.04～1.38,P=0.01).结论:中国人群中XRCC1基因Arg399Gln (G/A)多态性与神经胶质瘤的易感性存在相关性.     

XRCC1基因和肿瘤

肿瘤是一类多因素引发的疾病 ,表现为细胞数量和结构上的异常。研究显示许多基因在肿瘤的发生发展中起着关键性的作用 ,其中研究最多的是抑癌基因 ,癌基因以及DNA修复基因。DNA作为一种遗传物质 ,承担着传递遗传信息的重要任务 ,这意味着DNA必须保持相对的稳定性。然而从DNA的结构可以发现 ,DNA是一种相对比较活跃的物质 ,会发生自发性的损害 ,另外 ,DNA还必须承受来自内外环境的一些伤害 ,这些损伤打破了DNA的相对稳定性 ,导致一些突变的积聚 ,进而可能导致肿瘤的发生[1] 。而DNA修复系统通过逆转DNA损伤 ,在维持正常的细胞进程…     

XRCC1 R399Q基因多态性与结直肠癌易感性的Meta分析

目的探讨X—rayrepair cross—complementing group1（XRCC1）RB99Q基因多态性与结直肠癌易感性的关系。方法通过计算机检索和手工检索,收集有关XRCC1 R399Q基因多态性与结直肠癌易感性关系的文献,筛选出符合条件的文献,应用Meta分析软件对各项研究进行异质性检验,计算合并OR值及其95％可信区间,并行敏感性分析和发表偏倚的评估。结果国内外共有21篇文献纳入研究（结直肠癌组6229例;对照组10692例）。Meta分析结果显示：XRCC1 R399Q基因多态性在整个人群中与结直肠癌无明显的关联性（OR QQvs、RR=1．10,95％CI=0．90～1．35;OR QQ/RQvs.RR=1．02,95％CI=0．90～1．16;OR QQvs.RR/RQ=1．12,95％CI=0．95～1．33）。通过种族的分层分析发现XRCC1 R399Q基因多态性与结直肠癌易感性在亚洲人群和欧洲人群中无差异。结论XRCC1 R399Q基因多态性与结直肠癌间不存在明显的易感性。     

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。     

XRCC1基因多态与肿瘤遗传易感性研究进展

X射线交错互补修复基因1(XRCC1)通过直接与聚合酶β、DNA连接酶Ⅲ和多聚ADP核糖聚合酶形成复合物，共同参与因电离辐射和氧化损伤引起的碱基切除修复和单链断裂修复。XRCC1基因中存在3个单核苷酸多态位点，各位点多态对各种肿瘤遗传易感性的影响不一。现对XRCC1基因多态与某些肿瘤遗传易感性进行综述。     

XRCC1单核苷酸多态性与结直肠癌风险的关系

背景与目的:X线交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)编码蛋白在DNA单链断裂修复和DNA碱基修复过程中起重要作用.该基因外显子多态性的存在可影响编码蛋白的功能活性,最终使机体对癌症的易感性发生变化.本研究旨在探讨该基因外显子最常见的3处单核苷酸多态(single nucleotide polymorphism,SNP)--C26304T、G27466A和G28152A与结直肠癌风险的关系.方法:以聚合酶链反应(polymerase chain reaction,PCR)和限制性片段长度多态性(restrictive fragment length polymorphism,RFLP)分析方法,检测207例结直肠癌病例和621例成组匹配的正常对照XRCC1 C26304T、G27466A和G28152A基因型,并比较不同基因型与结直肠癌风险的关系.采用EH Linkage Software 1.2统计分析软件对研究对象的单体型分布进行预测.结果:年龄、性别、身体质量指数(body mass index,BMI)等个体特征,以及吸烟、饮酒等常见环境暴露因素的分布和/或构成比在结直肠癌病例组和对照组间差异均无显著性(P＞0.05).对XRCC1各多态基因型检测分型发现,结直肠癌病例组携带26304T、27466A和28152A变异等位基因的频率分别为29.95%、11.22%和28.22%,对照组分别为32.87%、12.34%和27.27%,各多态等位基因在两组间分布均没有显著性差异(P＞0.05).各多态基因型分布经x2拟合优度检验均符合Hardy-Weinberg平衡定律,且在两组间都没有显著性差异(P＞0.05).没有观察到各多态基因型与结直肠癌发病风险存在显著相关关系(P＞0.05).单体型分析发现,各变异等位基因在病例组和对照组内均存在遗传连锁不平衡现象,CGG、CGA、CAG和TGG是最常见的4类单体型,其在两组的分布频率总和分别为95.54%和96.64%,然而在两组间同样不存在显著性差异(P＞0.05).结论:我国浙江省嘉善县人群中,XRCC1 C26304T、G27466A和G28152A基因多态性与结直肠癌发病风险不存在相关性,然而各变异等位基因存在遗传连锁不平衡现象,CGG、CGA、CAG和TGG是最常见的4类单体型.     

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。     

DNA损伤修复基因XRCC和hOGG1多态性与肺癌易感性的关系

DNA损伤修复基因的多态性能够改变DNA修复功能和效率,影响肿瘤易感性.许多研究报道DNA损伤修复基因多态性可能与肿瘤易感性有关,其突变在多种肿瘤的发生、发展过程中起着重要作用.另外,DNA损伤修复基因可能与其他基因相互作用,共同影响肿瘤的发生、发展.肺癌是目前在这方面被研究得最多的肿瘤.文章就DNA损伤修复基因XRCC和hOGG1多态性的生物学特点以及这些基因单核苷酸多态性与肿瘤易感性等方面进行了综述,为该基因用于肿瘤的预防、诊治提供理论借鉴.     

Association Between XRCC1 Gene Polymorphisms and Risk of Glioma Development: A Meta-analysis

Objective: Previous studies of the association between X-ray cross-complementing group 1 (XRCC1) genepolymorphisms and the gliomas risk have yielded conflicting results, and thus a meta-analysis was performedto provide a more accurate estimation. Methods: A computerized literature search of 5 electronic databases wasconducted to identify the relevant studies. Fixed or random effect models were selected based on the heterogeneitytest. Publication bias was estimated using Begg’s funnel plots and Egger’s regression test. Results: A total of 11studies (3,810 cases and 6,079 controls), 7 studies (2,928 cases and 5,048 controls), and 4 studies (1,461 cases and2,593 controls) were finally included in the analyses of the association between XRCC1 Arg399Gln, Arg194Trp,and Arg280His polymorphisms and glioma risk, respectively. The pooled results showed that GlnGln carriagewas associated with moderately increased risk of gliomas in Asians (GlnGln vs. ArgArg, OR=1.490, 95%CI1.031-2.153; GlnGln/ArgGln vs. ArgArg, OR=1.321, 95%CI 1.037- 1.684), whereas a marginal association wasrevealed in Caucasians. For the Arg194Trp polymorphism, although a significant association was shown inthe homozygous genotype comparisons (TrpTrp vs. ArgArg, OR = 2.209, 95%CI 1.398- 2.945), no significantlink was found on subgroup analysis stratified by ethnicity. With regard to the Arg280His polymorphism, nosignificant association was found in each comparison. No particular study was found to significantly influencethe pooled results, and no potential publication bias was detected. Conclusions: This meta-analysis suggestedthat the XRCC1 Arg399Gln polymorphism is moderately associated with increased risk of gliomas in Asians,while Arg194Trp and Arg280His polymorphisms demonstrated no significant influence. Due to the limited studiesand the potential confounders, further studies are needed to confirm these results.     

Polymorphisms of the XRCC1 and XPD Genes and Breast Cancer Risk: A Case-Control Study

The purpose of this case control study was to evaluate the role of X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD) genotypes as genetic indicators of susceptibility to breast cancer (BC). We analysed DNA samples from 114 breast cancer patients and 113 control subjects using polymerase chain reaction-restriction fragment length polymorphism. For the single nucleotide polymorphisms in XRCC1 exon 10 (Arg399Gln, G/A) and XPD exon 23 (Lys751Gln, A/C), no remarkable differences for genotype distribution and allele frequencies were observed between BC group and control group in the study. The genotype frequency for homozygote A/A in XPD exon 6 (Arg156Arg, C/A) were significantly different between BC and control groups (P < 0.0001, odds ratio = 2.14; 95% confidence interval 1.44-3.17). The data indicate a possible role for XPD (Arg156Arg, C/A) polymorphisms in BC susceptibility.     

Genetic Polymorphisms of Glutathione S-transferase M1 and Prostate Cancer Risk in Asians: A Meta-analysis of 18 Studies

Background: Many studies have investigated associations between the glutathione S-transferase M1 (GSTM1)null polymorphism and risk of prostate cancer, but the impact of GSTM1 in people who live in Asian countries isstill unclear owing to inconsistencies across results. Methods: We searched the PubMed, Web of Science, Scopus,Ovid and CNKI databases for studies of associations between the GSTM1 null genotype and risk of prostatecancer in people who live in Asian countries, and estimated summary odds ratios (ORs) with 95% confidenceintervals (95% CIs). Results: A total of 18 case-control studies with 2,172 cases and 3,258 controls were includedin this meta-analysis, which showed the GSTM1 null genotype to be significantly associated with increased riskof prostate cancer in people who live in Asian countries (random-effects OR=1.74, 95% CI1.44-2.09, P<0.001).Similar results were found in East Asians (OR=1.41; 95% CI: 1.12–1.78; P=0.004) and Caucasians in Asia(OR=2.19; 95% CI: 1.85-2.60; P<0.001). No evidence of publication bias was observed. Conclusions: This metaanalysisof available data suggested that the GSTM1 null genotype does contribute to increased risk of prostatecancer in people who live in Asian countries.     

Association Between XRCC5, 6 and 7 Gene Polymorphisms and the Risk of Breast Cancer: A HuGE Review and Meta-analysis

Objective: Non-homologous end joining (NHEJ) is a pathway for repairing DNA double-strand breaks.Recent publications indicated that XRCC5, XRCC6 and XRCC7 genes may participate in the pathogenesis ofbreast cancer. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigateassociations between XRCC5, XRCC6 and XRCC7 genetic polymorphisms in the NHEJ pathway and breastcancer risk. Methods: Studies focusing on the relationship between genetic polymorphisms in XRCC5, XRCC6and XRCC7 genes and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase,Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers.The meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Theodds ratio (OR) with 95% confidence interval (95%CI) was calculated based on the extracted data. Results:According to the inclusion criteria, we final included seven studies with a total of 2,864 breast cancer cases and3,060 healthy controls. Meta-analysis results showed that rs3835 (G>A) and rs828907 (G>T) in XRCC5 gene,and rs132793 (G>A) in XRCC6 gene might increase the risk of breast cancer, while rs132788 G>T and rs6002421(A>G) might be protective factors. However, there was no relationship between XRCC7 genetic polymorphismsand the risk of breast cancer. Conclusion: This meta-analysis suggests that the rs3835 G>A and rs828907 G>Tin XRCC5 gene, rs6002421 (A>G), rs132788 (G>T) and rs132793 (G>A) in XRCC6 gene might be risk factorsfor breast cancer, while the rs132788 (G>T) and rs6002421 (A>G) in XRCC6 gene might be protective.     

Association of XRCC3 Thr241Met Polymorphisms and Gliomas Risk: Evidence from a Meta-analysis

The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphismand gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Metpolymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through asearch of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese BiomedicalLiterature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphismand gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of ninecase-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found thatXRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10,95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC: OR=1.29,95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was foundin Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36-2.36, P=0.00; TT vs. TC/CC: OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20).This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especiallyfor Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scaleand well-designed studies are needed to confirm our results.     

XRCC1基因G28152A多态与肺癌风险的研究

背景与目的 :研究碱基切除修复基因XRCC1基因G28152A单核苷酸多态与肺癌风险的关系。材料与方法 :以病例_对照研究方法 ,采用聚合酶链反应一限制性片段长度多态性法检测肺癌病例(n=149)和按性别、年龄频数匹配的正常对照(n=157)XRCC1基因G28152A多态 ,分析各基因型与肺癌易感性的关系。 结果 :肺癌患者中 ,XRCC1基因28152AA突变基因型频率为15.4 % ,高于对照组7.6 % ;此基因型个体发生肺癌风险是其他基因型个体的2.2倍(95 %CI1.06～4.61)。 结论 :XRCC1基因G28152A多态可能在肺癌发生中起一定作用。     

Association of Functional Polymorphisms of the XRCC4 Gene with the Risk of Breast Cancer: A Meta-analysis

Objective: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for DNA double-strand breaks(DSB) in the non-homologous end-joining (NHEJ) pathway. Several potentially functional polymorphisms of theXRCC4 gene have been implicated in breast cancer risk, but individually published studies showed inconclusiveresults. The aim of this meta-analysis was to investigate the association between XRCC4 polymorphisms and therisk of breast cancer. Methods: The MEDLINE, EMBASE, Web of science and CBM databases were searchedfor all relevant articles published up to June 20, 2012. Potential associations were assessed with comparisons ofthe total mutation rate (TMR), complete mutation rate (CMR) and partial mutation rate (PMR) in cases andcontrols. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 software. Results: Five studieswere included with a total of 5,165 breast cancer cases and 4,839 healthy controls. Meta-analysis results showedthat mutations of rs2075686 (C>T) and rs6869366 (G>T) in the XRCC4 gene were associated with increasedrisk of breast cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of breast cancer.However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del) and rs3734091 (A>G) polymorphisms ofXRCC4 gene did not appear to have an influence on breast cancer susceptibility. Conclusion: Results from thecurrent meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms of the XRCC4 genemight increase the risk of breast cancer, whereas rs2075685 (G>T) and rs10057194 (A>G) might be protectivefactors.     

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.     

MTHFR Gene Polymorphisms are Not Involved in Pancreatic Cancer Risk: A Meta-analysis

Purpose: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to beassociated with pancreatic cancer, but the published studies have yielded inconsistent results. This study assessedthe relationship between MTHFR gene polymorphisms and the risk for pancreatic cancer using a meta-analysisapproach. Methods:A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012was performed, and then associations of the MTHFR polymorphisms with pancreatic cancer risk were summarized.The association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was alsocalculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were included inthis meta-analysis. Overall, C667T (TT vs. CC:OR=1.61,95%CI=0.78-3.34; TT vs. CT: OR=1.41,95%CI=0.88-2.25;Dominant model:OR=0.68,95%CI=0.40-1.17; Recessive model: OR=0.82,95%CI=0.52-1.30) and A1298C (CCvs. AA:OR=1.01,95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14; Dominant model:OR=1.01,95%CI=0.47-2.20; Recessive model: OR=1.01,95%CI=0.80-1.26) did not increase pancreatic cancer risk.Conclusions: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) are not associatedwith pancreatic cancer risk.     

Polymorphisms in the XRCC1 gene modify survival of bladder cancer patients treated with chemotherapy

Survival of bladder cancer patients depends on several factors including disease stage and grade at diagnosis, age, health status of the patient and the applied treatment. Several studies investigated the role of DNA repair genetic variants in cancer susceptibility, but only few studies investigated their role in survival and response to chemotherapy for bladder cancer. We genotyped 28 single nucleotide polymorphisms (SNP) in DNA repair genes in 456 bladder cancer patients, reconstructed haplotypes and calculated a score for combinations of the SNPs. We estimated Hazard Ratios (adjHR) for time to death. Among patients treated with chemotherapy, variant alleles of five SNPs in the XRCC1 gene conferred better survival (rs915927 adjHR 0.55 (95%CI 0.32–0.94); rs76507 adjHR 0.48 (95%CI 0.27–0.84); rs2854501 adjHR 0.25 (95%CI 0.12–0.52); rs2854509 adjHR 0.21 (95%CI 0.09–0.46); rs3213255 adjHR 0.46 (95%CI 0.26–0.80). In this group of patients, an increasing number of variant alleles in a XRCC1 gene score were associated with a better survival (26% decrease of risk of death for each additional variant allele in XRCC1). By functional analyses we demonstrated that the previous XRCC1 SNPs confer lower DNA repair capacity. This may support the hypothesis that survival in these patients may be modulated by the different DNA repair capacity determined by genetic variants. Chemotherapy treated cancer patients bearing an increasing number of “risky” alleles in XRCC1 gene had a better survival, suggesting that a proficient DNA repair may result in resistance to therapy and shorter survival. This finding may have clinical implications for the choice of therapy.