Genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 and risk of colorectal cancer in Chinese population

Aim: The distribution of DNA repair gene XRCC1 and XRCC3 genotypes was used to assess the potential influence of genetic polymorphisms on risk of colorectal cancer, and interactions with other factors. Methods: a 1:2 matched case-control study was conducted with 485 cases and 970 controls. XRCC1 and XRCC2 genotype polymorphisms were based upon duplex polymerase-chain-reaction with the confronting-two-pairprimer (PCR-CTPP) method. Results:The XRCC1 399Cln allele polymorphism was found to be associated with an increased colorectal cancer risk, while an non-significant inversely association was noted for XRCC3 241Thr/Thr genotype. We also found that individuals with the XRCC1 399 Gln and XRCC3 241Met alleles had an elevated risk, while XRCC3241Thr/Thr was proctective. Conclusion: This study is the first to provide evidence of importance of XRCC1 and XRCC3 gene polymorphisms for risk of colorectal cancer in the Chinese population.     

Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus

Population-based studies have reported significant associations between specific genetic polymorphisms and breast cancer susceptibility. A number of studies have demonstrated that common variants of genes involved in the DNA repair pathway act as low penetrance breast cancer susceptibility alleles. We aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the DNA repair genes XRCC1, XRCC2 and XRCC3 and breast cancer in MASTOS, a population-based case–control study of 1,109 Cypriot women with breast cancer diagnosed between 40 and 70 years and 1,177 age-matched healthy controls. Five coding SNPs were genotyped including rs1799782, rs25489 and rs25487 in XRCC1, rs3218536 in XRCC2 and rs861539 in XRCC3. Homozygous XRCC1 280His carriers had an increased risk of breast cancer (odds ratio 4.68; 95% CI 1.01–21.7; P = 0.03). The XRCC2 188His allele was associated with a marginal protective effect for breast cancer (odds ratio 0.79; 95% CI 0.62–1.00; P = 0.05). No significant associations were observed between the other three SNPs and breast cancer. This study suggests that genetic variation in SNPs in XRCC1 and XRCC2 genes may influence breast cancer susceptibility.     

DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and XRCC1 polymorphisms, and bladder cancer risk.

DNA repair efficiency varies among individuals, with reduced repair capacity as a risk factor for various cancers. This variability could be partly explained by allelic variants for different DNA repair genes. We examined the role of a common polymorphism in the XRCC3 gene (codon 241: threonine to methionine change) and bladder cancer risk. This gene plays a role in the homologous recombination pathway, which repairs double-strand breaks. The functional consequences of the XRCC3 codon 241 polymorphism are still unknown. We hypothesized that this polymorphism could affect repair of smoking-associated DNA damage and could thereby affect bladder cancer risk. We genotyped 233 bladder cancer cases and 209 controls who had been frequency matched to cases on age, sex, and ethnicity. We observed little evidence of a positive association between subjects who carried at least one copy of the codon 241 Met allele and bladder cancer (odds ratio: 1.3; 95% confidence interval: 0.9-1.9). Among heavy smokers, individuals with the Met allele had about twice the risk of those without it; however, a test of interaction was not statistically significant (P = 0.26). Previously, we observed in these subjects an association between bladder cancer risk and allelic variants of the XRCC1 gene, which is involved in the repair of base damage and single-strand breaks. In this study, we found some evidence for a gene-gene interaction between the XRCC1 codon 194 and XRCC3 codon 241 polymorphisms (P = 0.09) and some support for a possible gene-gene-smoking three-way interaction (P = 0.08).     

Polymorphisms of DNA repair genes, XRCC1 and XRCC3, and susceptibility to familial prostate cancer in a Japanese population

Aim: DNA repair systems play an important role in protecting the genome damaged by endogeneous and exogeneous mutagens. Deficiency in these systems has been reported to increase the risk of various types of cancer. We investigated two DNA repair genes, X‐ray repair cross‐complementing group 1 (XRCC1) and X‐ray repair cross‐complementing group 3 (XRCC3), to assess the association between DNA repair genes and familial prostate cancer susceptibility in the Japanese population. Methods: We performed a case‐control study consisting of 142 familial prostate cancer cases and 119 normal control subjects. The genetic polymorphism was analyzed by the polymerase chain reaction‐restriction fragment length polymorphism method. Results: Of the three polymorphisms investigated, the frequency of the XRCC1 codon 194 Arg/Trp genotype, was significantly observed in cases (odds ratio [OR] = 2.19, 95% confidence interval [CI] = 1.28–3.73, P = 0.0058) and the Arg/Trp and Trp/Trp genotypes were also significantly observed in cases (OR = 2.03, 95% CI = 1.23–3.36, P = 0.0080). For the Arg399Gln genotype in XRCC1 and the Thr241Met genotype in XRCC3, no significant differences were observed between cases and controls. Stratification of cases according to clinical stages and pathological grades showed no significant difference among clinical parameters and genotypes. Conclusion: The Trp allele in the XRCC1 codon 194 was significantly associated with individuals in the Japanese population with a family history of prostate cancer.     

Comprehensive assessment of the association between DNA repair gene XRCC3 rs861539 C/T polymorphism and lung cancer risk

A few case–control studies were performed to assess the association between X-ray repair cross-complementing group 3 (XRCC3) rs861539 C/T polymorphism and lung cancer susceptibility, but no consistent finding was reported. In the present study, we performed a meta-analysis of 14 case–control studies with a total of 7,869 lung cancer cases and 10,778 controls to provide a comprehensive assessment of the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Overall, there was no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models [OR (95 % CI) for T versus C, 1.00 (0.89–1.13), P?=?0.99; OR (95 % CI) for TT versus CC, 1.07 (0.81–1.41), P?=?0.62; OR (95 % CI) for TT/CT versus CC, 0.95 (0.84–1.07), P?=?0.39; OR (95 % CI) for TT versus CT/CC, 1.10 (0.86–1.39), P?=?0.62]. In the subgroup analyses of both Asians and Caucasians, there was still no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models (All P values were more than 0.05). However, there was an obvious association between XRCC3 rs861539 C/T polymorphism and decreased risk of lung cancer in the subgroup analysis of the mixed population (All P values were less than 0.05). In addition, there was some risk of publication bias in the meta-analysis, and there was obvious discrepancy in the findings between studies with large sample size and studies with small sample size in the meta-analysis. The meta-analysis indicates that the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk is still uncertain owing to the obvious discrepancy in the findings between studies with large sample size and studies with small sample size. More studies with large sample size are needed to further assess the association.     

DNA损伤修复基因XRCC3 Thr241Met多态与肺癌易感性关系的Meta分析

目的:探讨DNA损伤修复基因X射线交叉互补修复基因3(XRCC3)Thr241Met多态性与肺癌易感性的关系。方法:查找中国医学文献数据库和PubMed,以得到XRCC3基因Thr241Met多态与肺癌易感性关系的病例-对照研究,根据纳入和排除标准筛选符合条件的研究进行Meta分析,合并XRCC3基因Thr241Met多态与肺癌易感性关系的OR值,然后进行亚组分析、敏感性分析和文献的发表偏倚检验。结果:本次Meta分析共纳入13篇文献,累计病例2 986例,对照4 495例,显性模型下TM+MM基因型相对于TT(TM=Thr/Met)基因型OR值为0.96(95%CI为0.86~1.06),差异无统计学意义。结论:尚无足够证据证明XRCC3基因Thr241Met多态同肺癌易感性有关。     

Comprehensive assessment of the association between DNA repair gene XRCC3 Thr241Met polymorphism and leukemia risk

The XRCC3 gene has been suggested to play an important role in the pathogenesis of leukemia risk. But the findings of publications are contradictory. To derive a more precise estimation of the association, we performed a meta-analysis. The PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched for case–control studies published up to August 2013. The pooled odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated by using a fixed- or random-effect model. A total of 15 case–control studies met the inclusion criteria and were selected. The pooled OR showed that there was no statistically significant association between XRCC3 Thr241Met polymorphism and leukemia risk in overall including studies, while a risky association was observed for acute myeloid leukemia (AML) (dominant model TT/TC vs. CC: OR = 1.240, 95 % CI = 1.018–1.511, P = 0.032). The XRCC3 Thr241Met polymorphism might be associated with risk of leukemia in AML. More studies with larger sample sizes are needed to validate this result.     

Mouse models of XRCC1 DNA repair polymorphisms and cancer

DNA damage plays a major role in mutagenesis, carcinogenesis and aging. A gene that is emerging as an essential element in the repair of both damaged bases and single-strand breaks (SSB) is XRCC1. XRCC1 has been shown to have a large number of single-nucleotide polymorphisms (SNPs), several of which are being increasingly studied in cancer epidemiology investigations, in part because of their relative high frequency in the population. Although association trends with specific cancer types have occasionally been shown in a variety of ethnic backgrounds, there are often conflicting reports that weaken any substantial conclusions. The functional significance of these SNPs is still largely unknown. XRCC1 is an excellent prototype to provide a forum for determining how epidemiological cancer association studies with DNA repair gene polymorphisms can be validated or refuted. The focus is on the utilization of in silico data and biochemical studies in cell lines and existing mouse models to help provide a framework for the development of new mutant mouse lines that mimic human polymorphisms. These mouse lines will provide the next generation of mammalian tools for carcinogen exposure studies relevant to human cancer and variations in XRCC1, and provide the basis for investigating groups of genes and polymorphisms in an animal model.     

Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer

Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are two major DNA base excision repair (BER) proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT Val762Ala and XRCC1 Arg399Gln have been associated with altered protein function and BER activity. This case-control study examined the contribution of these two polymorphisms, alone and in combination, or in interaction with smoking, to the risk of developing lung cancer. We estimated the risk of lung cancer associated with these polymorphisms in 1,000 cases and 1,000 cancer-free controls using logistic regression models. Subjects having the ADPRT Ala/Ala genotype had an odds ratio (OR) of 1.68 [95% confidence interval (95% CI), 1.27-2.23] compared with those having the Val/Val genotype. A greater than multiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CI) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or =16, 16 to 28, or >28 pack-years were 1.13 (0.79-1.62), 1.35 (0.68-2.70), 2.46 (1.35-4.51) or 17.09 (8.15-35.83), respectively (P trend test < 0.001). Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased risk of lung cancer in a supermultiplicative manner (OR for the presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, 5.91; 95% CI, 2.09-16.72), although the XRCC1 polymorphism itself was not associated with the risk. In conclusion, the ADPRT Val762Ala polymorphism plays an important role in smoking-related lung cancer and the XRCC1 Arg399Gln polymorphism may serve as a risk modifier.     

Variation in DNA repair genes ERCC2, XRCC1, and XRCC3 and risk of follicular lymphoma.

The reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms.     

非小细胞肺癌NP方案化疗敏感性与DNA修复基因XRCC1多态性的关系

背景与目的:基因多态预测肿瘤化疗药物敏感性对肿瘤个体化治疗具有重要意义。本研究旨在探讨DNA修复基因XRCC1 codon194及399位点基因多态性与非小细胞肺癌长春瑞滨加顺铂(vinorelbine and cisplatin,NVB and DDP,NP)方案化疗敏感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性技术检测164例非小细胞肺癌患者外周血DNAXRCC1194和399位点的多态性。选择NP方案化疗,化疗两周期后评价疗效,并分析化疗敏感性与基因多态性的关系。结果:携带XRCC1基因Codon194C/T+T/T基因型者化疗有效率(41.8%)是C/C基因型者(26.0%)的2.038倍(P=0.036,95%CI=1.044-3.976)。携带XRCC1基因Codon399G/G、A/G、A/A型的患者化疗有效率(37.1%,34.6%,14.3%)之间的差异无统计学意义(P>0.05)。应用分析软件SHEsis发现以     

DNA修复基因XRCC1单核苷酸多态性与非霍奇金淋巴瘤遗传易感性的关系

 目的　探讨DNA修复基因XRCC1 R280H、XRCC1 TSS+29C／T单核苷酸多态性与非霍奇金淋巴瘤（NHL）易感性的关系。方法　运用MassARRAY技术对73例NHL病例和540名健康对照的DNA修复基因XRCC1多态性进行检测,比较其不同基因型与淋巴瘤患病风险的关系。结果　XRCC1 R280H中G、A基因频率在对照组和病例组中分布差异有统计学意义（P＝0.001）,而XRCC1 TSS+29C／T中T、C的基因频率在两组中的分布差异无统计学意义 （P＝0.383）。进一步的分析表明,在XRCC1 R280H中,与携带GG野生纯合子基因型者比较,携带至少一个A等位基因者（GA或AA）患淋巴瘤的风险显著降低（P＜0.001,OR＝0.309,95 % CI＝0.168～0.567）。而在XRCC1 TSS+29C／T中,CC和CT与基因TT比较,携带C基因者会增加淋巴瘤的发病风险（P＝0.472,OR＝1.262,95 % CI＝0.669～2.379）。结论　DNA修复基因XRCC1 R280H的基因多态性与NHL的发生密切相关。     

Association between XRCC3 Thr241Met polymorphism and colorectal cancer risk

The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case–control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (OR_{Met allele vs. Thr allele}?=?1.17, 95 % CI 0.97–1.42, P _OR?=?0.102; OR_{MetMet vs. ThrThr}?=?1.32, 95 % CI 0.93–1.87, P _OR?=?0.121; OR_{ThrMet vs. ThrThr}?=?1.17, 95 % CI 0.94–1.45, P _OR?=?0.150; OR_{MetMet + ThrMet vs. ThrThr}?=?1.20, 95 % CI 0.96–1.51, P _OR?=?0.114; OR_{MetMet vs. ThrThr + ThrMet}?=?1.37, 95 % CI 0.98–1.93, P _OR?=?0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case–control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.     

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.     

DNA修复基因XPD XPC XRCC4基因多态性与结直肠癌易感性的关联性研究

  目的  探讨DNA修复基因XPD rs13181（codon751A/C,Lys751Gln）、rs238406（codon156C/A,Arg156Arg）、XPC rs2279017（i11C/A）和XRCC4 rs3734091（codon247T/C,Ala247Ser）的单核苷酸多态性与结直肠癌易感性的关系。  方法  采用TaqMan技术对2013年4月至2016年1月北京肿瘤医院收治的338例结直肠癌患者（病例组）和315例健康者（对照组）进行多态位点基因型的检测。  结果  XPD rs13181基因型GT和等位基因G增加个体结直肠癌的发病风险（GT>TT,adjusted OR=1.69,95%CI:1.15~2.47,P=0.007;G>T,adjusted OR=1.77,95%CI:1.19~2.64,P=0.005）;XRCC4 rs3734091基因型GT和等位基因T增加个体结直肠癌的易感性（GT>GG,adjusted OR=9.02,95%CI:5.61~14.50,P＜0.001;T>G,adjusted OR=4.06,95%CI:2.49~6.61,P＜0.001）;XPD rs13181和rs238406的单倍体型GT显著降低结直肠癌的发病风险（adjusted OR=0.39,95%CI:0.18~0.85,P=0.018）。XPCrs2279017等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=28.43,95%CI:6.85~117.95,P＜0.001）以及XPD rs13181等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=10.24,95%CI:4.69~22.35,P＜0.001）显著增加个体结直肠癌的易感性。  结论  XPD rs13181和XRCC4 rs3734091位点的多态性与结直肠癌的易感性相关。      

Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk for lung cancer in never- and ever-smokers

This case-control study examines the association between lung cancer and genetic polymorphisms in two base excision repair (BER) genes, XRCC1 and APEX1 and two genes involved in homologous recombination repair (HR), XRCC3 and NBS1. Never-smoking lung cancer patients were recruited, and also the next diagnosed ever-smoking case of the same gender and age group. Controls were recruited from the regional population register, frequency matched to cases by hospital catchment area, gender, age group and smoking category. As a result more than 70% of the study population were women. A total of 331 individuals were analysed. Presence of the XRCC1 399Gln allele was associated with a significantly decreased risk for lung cancer among non-smoking women (odds ratio (OR) 0.4, 95% confidence interval (CI) 0.2-0.9). No significant effect was seen with the APEX1 polymorphism. Women smokers carrying the XRCC3 241Met allele showed a significantly decreased risk for lung cancer (OR 0.3, CI 0.2-0.7). The NBS1 185Gln allele was significantly associated with an increased risk for lung cancer among non-smoking women (OR 2.2, CI 1.0-4.8) and low-dose smoking women (OR 4.8, CI 1.5-15.7). The protective effect of the variant XRCC3 241Met allele was strengthened when combined with the low-risk Glu185 allele of the NBS1 gene. Smokers (OR 0.38, CI 0.16-0.90) and women (OR 0.42, CI 0.21-0.85) with at least three low-risk alleles in these two HR genes showed a significantly decreased risk for lung cancer. Thus, in spite of a relatively small study population, this study, including a comparatively large number of never-smokers and women, presents several novel aspects on genetic susceptibility to lung cancer. Our results show that the genetic variation in XRCC1, XRCC3 and NBS1 influence lung cancer susceptibility among women, and that combinations of risk alleles in the two HR genes can enhance the effects.     

Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer

Mammalian cells are constantly exposed to a wide variety of genotoxic agents from both endogenous and exogenous sources. Genetic variability in DNA repair may contribute to human cancer risk. We used a case-control study design (162 cases and 302 controls) to test the association between three amino acid substitution variants of DNA repair genes (XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 Thr241Met) and breast cancer susceptibility. We found a weak association between the XRCC1 194Trp allele and breast cancer risk (adjusted odds ratio (OR)=1.98; 95% confidence interval (CI)=0.85–4.63). We also found a potential gene-gene interaction between the XRCC1 194Trp allele and XRCC3 241Met allele and breast cancer risk (adjusted OR=8.74; 95% CI=1.13–67.53). Although larger studies are needed to validate the study results, our data suggest that amino acid substitution variants of XRCC1 and XRCC3 genes may contribute to breast cancer susceptibility.     

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。     

DNA repair gene XRCC3 Thr241Met polymorphism and hepatocellular carcinoma risk

The DNA repair genes have been indicated as candidates in the risk of hepatocellular carcinoma (HCC). Published data on the association between X-ray repair cross-complementing group 3 (XRCC3), a critical member of the DNA repair genes, and HCC risk were contradictory. The aim of this meta-analysis was to assess the effect of XRCC3 Thr241Met polymorphism on HCC risk by pooling available data from published case–control studies. We calculated the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) to estimate the effect. Based on the inclusion criteria, six individual studies with 2,288 cases and 3,170 controls were included into our study. Overall, significant association between the XRCC3 Thr241Met variant and HCC risk was observed under the following contrast models (OR_{Met vs. Thr}?=?1.68, 95 %CI 1.08–2.62; OR_{MetMet vs. ThrThr}?=?5.54, 95 %CI 3.09–9.94; OR_{MetMet vs. ThrThr?+?ThrMet}?=?5.70, 95 % CI 4.24–7.64). Besides, the pooled ORs indicated that the XRCC3 Thr241Met polymorphism exerted risk effect on the HCC pathogenesis among Asians. Additionally, when stratifying by the status of smoking and hepatitis B virus infection, the XRCC3 Thr241Met variant was significantly associated with HCC risk among the HBsAg (+) individuals but not the HBsAg (?) individuals, smokers, and non-smokers. The present meta-analysis suggests that the XRCC3 Thr241Met polymorphism is an independent risk factor for HCC, particularly among Asians and the HBsAg (+) individuals.