Associations Between XRCC1 Arg399Gln,Arg194Trp,and Arg280His Polymorphisms and Risk of Differentiated Thyroid Carcinoma: A Meta-analysis

Background: Associations between Arg399Gln, Arg194Trp and Arg280His polymorphisms of the XRCC1 geneand risk of differentiated thyroid carcinoma (DTC) have been widely studied but the findings are contradictory.Methods: We performed a meta-analysis in the present study using STATA 11.0 software to clarify any associations.Electronic literature databases and reference lists of relevant articles revealed a total of 10, 6 and 6 publishedstudies for the Arg399Gln, Arg194Trp and Arg280His polymorphisms, respectively. Results: No significantassociations were observed between Arg399Gln and DTC risk in all genetic models within the overall andsubgroup meta-analyses, while the Trp/Trp vs Arg/Arg and recessive model of the Arg194Trp polymorphismwas associated with DTC susceptibility, and the dominant model of Arg280His polymorphism contributed toDTC susceptibility in Caucasians. Conclusions: Our meta-analysis suggests that XRCC1 Arg194Trp may be arisk factor for DTC development.     

Association of the Arg194Trp and the Arg399Gln Polymorphisms of the XRCC1 Gene With Risk Occurrence and the Response to Adjuvant Therapy Among Polish Women With Breast Cancer

BackgroundThe XRCC1 gene encoding the X-ray cross-complementing group 1 protein (XRCC1) is involved in the base excision repair (BER) pathway.MethodsThe aim of this study was to investigate an association of the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene with a risk of breast cancer occurrence and the response to adjuvant treatment among Polish women. Overall survival (OS) and disease-free survival (DFS) were investigated in groups of patients with breast cancer treated with (1) all types of adjuvant therapy, (2) concomitant radiotherapy and chemotherapy, (3) chemotherapy alone, or (4) radiotherapy alone. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to evaluate the genotype distribution of the XRCC1 gene among 185 patients with breast cancer and 205 female controls.ResultsWe showed a higher risk of breast cancer occurrence for the Trp allele and the Arg194Trp genotype of the XRCC1 gene. However there was no significant difference in distribution of the Arg399Gln genotype of XRCC1 between patients and the control group. In the patient subgroup treated with adjuvant therapy, Kaplan-Meier survival analysis showed a significantly higher OS as well as DFS for carriers of the Gln399Gln genotype when compared with carriers of the Arg399Gln and Arg399Arg genotypes. The Gln399Gln genotype was associated with a significantly higher DFS in the subgroup of patients treated with chemotherapy alone or with concomitant radiotherapy and chemotherapy.ConclusionWe suggest that the polymorphism of the XRCC1 gene may be considered a predictive factor associated with the risk of occurrence and the survival outcome in breast cancer among Polish women.     

Distribution and Haplotype Associations of XPD Lys751Gln,XRCC1 Arg280His and XRCC1 Arg399Gln Polymorphisms with Nasopharyngeal Carcinoma in the Malaysian Population

Background: DNA repair pathways play a crucial role in maintaining the human genome. Previous studiesassociated DNA repair gene polymorphisms (XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln)with nasopharyngeal carcinoma. These non-synonymous polymorphisms may alter DNA repair capacity andthus increase or decrease susceptibility. The present study aimed to determine the genotype distribution of XPDcodon 751, XRCC1 codon 280 and codon 399 polymorphisms and haplotype associations among NPC cases andcontrols in the Malaysian population. Materials and Methods: We selected 157 NPC cases and 136 controls fromtwo hospitals in Kuala Lumpur, Malaysia for this study. The polymorphisms studied were genotyped by PCRRFLPassay and allele and genotype frequencies, haplotype and linkage disequilibrium were determined usingSNPstat software. Results: For the XPD Lys751Gln polymorphism, the frequency of the Lys allele was higher incases than in controls (94.5% versus 85.0%). For the XRCC1 Arg280His polymorphism, the frequency of Argallele was 90.0% and 89.0% in cases and controls, respectively and for XRCC1 Arg399Gln the frequency of theArg allele was 72.0% and 72.8% in cases and controls respectively. All three polymorphisms were in linkagedisequilibrium. The odds ratio from haplotype analysis for these three polymorphisms and their associationwith NPC was 1.93 (95%CI: 0.90-4.16) for haplotype CGC vs AGC allele combinations. The global haplotypteassociation with NPC gave a p-value of 0.054. Conclusions: Our study provides an estimate of allele and genotypefrequencies of XRCC1Arg280His, XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in the Malaysianpopulation and showed no association with nasopharyngeal cancer.     

The XRCC1 Arg399Gln Gene Polymorphism and Risk of Colorectal Cancer: a Study in Kashmir

Background: The DNA repair gene XRCC1 Arg399Gln gene polymorphism has been found to be implicatedin the development of various cancers, including colorectal cancer (CRC), in different populations. We aimedto determine any association of this polymorphism with the risk of CRC in Kashmir. Materials and Methods:A total of 120 confirmed cases of CRC and 146 healthy cancer free controls from the Kashmiri population wereincluded in this study. Genotyping was carried out by the polymerase chain reaction- restriction fragment lengthpolymorphism (PCR-RFLP) method. Results: Genotype frequencies of XRCC1 Arg399Gln observed in controlswere 34.2%, 42.5% and 23.3% for GG (Arg/Arg), GA (Arg/Gln), AA( Gln/Gln), respectively, and 28.3%, 66.7%and 5% in cases, with an odds ratio (OR)=5.7 and 95% confidence interval (CI) =2.3-14.1 (p=0.0001). No significantassociation of Arg399Gln SNP with any clinicopathological parameters of CRC was found. Conclusions: Wefound the protective role of 399Gln allele against risk to the development of CRC. The XRCC1 heterozygotestatus appears to be a strong risk factor for CRC development in the Kashmiri population.     

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。     

Association Between Polymorphisms of XRCC1 Arg399Gln and XPD Lys751Gln Genes and Prognosis of Colorectal Cancer in a Chinese Population

We conducted this study to detect associations between XRCC1 Arg399Gln and XPD Lys751Gln genotypesand survival of colorectal cancer patients treated with 5-FU/oxalipatin chemotherapy. We included 289 Chinesepatients with advanced colorectal cancer, who had received 5-FU/oxalipatin chemotherapy as first-line treatmentfrom January 2005 to January 2007. All patients were followed up till Nov. 2011. Genotyping for XRCC1Arg399Gln and XPD Lys751Gln polymorphisms was based upon duplex polymerase-chain-reaction with thePCR-RFLP method. In our study, we found the XRCC1 399 Gln/Gln genotype to confer significantly higherrates of response to chemotherapy when compared to the Arg/Arg genotype [OR (95% CI)= 2.56(1.57-2.55)].patients with the XPD 751 Gln/Gln genotype had significantly higher rates of response to chemotherapy [OR(95% CI)= 1.54(0.87-2.65)] and those with the XRCC1 399 Gln/Gln genotype had a longer average survivaltime and significantly lower risk of death than did those with the Arg/Arg genotype [HR (95% CI)= 0.66(0.36-0.95)]. Similarly, those carrying the XPD 751Gln/Gln genotype had 0.51-fold the risk of death of those with XPD751Lys/Lys [HR (95% CI)= 0.51(0.33 -0.94)]. In conclusion, it is suggested that the XRCC1 Arg399Gln and XPDLys751Gln polymorphisms should be routinely assessed to determine colorectal patients who are more likely tobenefit from 5-FU/oxalipatin chemotherapy.     

The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians

Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair)pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repairefficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene(at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity andincreased genomic instability in multiple studies. Hence our investigation focused on genotyping these variantsto correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that thesevariants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined thefrequency of the polymorphism in one hundred cases and an almost equal number of controls after recordingtheir demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCRstudies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed.Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%),and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln toshow association with lung cancer. Correlating these genotypes with several parameters, we also found that thesetwo variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Glngenotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenariowhere Arg399Gln genotypes were found to be associated with stage of the disease in females. Conclusions: Itis concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients withsmoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lungcancer for diagnosis and prognosis.     

Association between the XRCC1 Arg194Trp Polymorphism and Glioma Risk: an Updated Meta-analysis

Gliomas are the most common type of primary brain tumors. The XRCC1 Arg194Trp variant affects the proliferating cell nuclear antigen( PCNA) binding region, which suggests that this mutation may contribute to gliomagenesis and a number of articles have examine the association between XRCC1 Arg194Trp and the susceptibility to glioma. However, the results were conflicting. Test of heterogeneity, sensitivity analysis, metaanalysis, and assessment of publication bias were all performed in our present meta-analysis, covering a total of5,407 patients and 7,715 healthy persons. In the overall analysis the XRCC1 Arg194Trp polymorphism showed a significant association with glioma susceptibility in a recessive mode l(for TrpTrp vs ArgArg+ArgTrp: OR=1.918,95%CI=1.575-2.336, I2=2.3%). In addition, analysis of subgroups presented an increased risk in Asians and populations-based on hospitals. The results suggested that the XRCC1 Arg194Trp polymorphism is a genetic risk factor for glioma, especially in Asian population. To further evaluate gene-gene and gene-environment interactions on XRCC1 polymorphisms and glioma risk, thousands of subjects and tissue-specific biochemical characterizations are required.     

Association of XRCC1 Arg399Gln Polymorphism with Colorectal Cancer Risk: A HuGE Meta Analysis of 35 Studies

Background: Non-synonymous polymorphisms in XRCC1 hase been shown to reduce effectiveness of DNArepair and be associated with risk of certain cancers. In this study we aimed to clarify any association betweenXRCC1 Arg399Gln and colorectal cancer (CRC) risk by performing a meta-analysis of published case-controlstudies. Materials and Methods: PubMed and Google Scholar were searched to explore the association betweenXRCC1 and CRC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate theassociation strength. Publication bias was assessed by Egger’s and Begg’s tests. Results: Up to January 2015, 35case control studies involving 9,114 CRC cases and 13,948 controls were included in the present meta-analysis.The results showed that the Arg399Gln polymorphism only under an allele genetic model was associated withCRC risk (A vs. G: OR 0.128, 95% CI 0.119-0.138, p<0.001). Also, this meta-analysis suggested that the XRCC1Arg399Gln polymorphism might associated with susceptibility to CRC in Asians (A vs G: OR 0.124, 95% CI0.112-0.138, p<0.001) and Caucasian (A vs G: OR 0.132, 95% CI 0.119-0.146, p<0.001) only under an allele geneticmodel. Conclusions: This meta-analysis confirms the association between XRCC1 Arg399Gln polymorphismand CRC risk and suggests that the heterogeneity is not strongly modified by ethnicity and deviation from theHardy-Weinberg equilibrium.     

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.     

Effect of XRCC1 Arg399Gln Gene Polymorphism on Survival in Lymphoblastic Leukemia

Introduction: The relevance of the research of the article is conditioned upon the problem of the development of molecular genetic diagnostics to determine the effectiveness of treatment for acute lymphoblastic leukemia in children. The purpose of the article is to identify the polymorphism parameters of the P53 Arg72Pro and XRCC1 Arg399Gln genes in acute lymphoblastic leukemia with criteria for determining the survival rates of sick children. Materials and methods: Methods for the study of the identified problem are the study of the medical histories of children with acute leukemia, which allowed selection of the necessary contingent of patients for further genetic study of their frozen blood, where the genomic part of deoxyribonucleic acid was isolated from the frozen blood in a standard way using molecular biological research when performing a polymerase chain reaction. Results: The article presents the results of a study that shows that in children with acute lymphoblastic leukemia, the frequency of genotypes of the XRCC1 Arg399Gln gene is variable. The most common genotypes are Arg/Gln and Arg/Arg, approximately 48% each. The Gln/Gln genotype is less common. Relapse-free survival of children with the Arg/Gln and Gln/Gln genotypes was the highest, slightly lower rates were noted with the Arg/Arg genotype. Conclusion: It was identified that the frequency of genotypes of the XRCC1 Arg399Gln gene can be a predictor of prognosis in acute lymphocytic leukemia in children, which can be considered when choosing treatment tactics, and this has practical significance for the field of medicine.     

Assessment of the association between XRCC1 Arg399Gln polymorphism and glioma susceptibility

The Arg399Gln polymorphism, located in the region of the BRCT-I interaction domain of XRCC1, has been extensively explored in its function and association with glioma risk. However, these studies generated contradictory instead of conclusive results. A meta-analysis was performed to derive a more precise evaluation of the relationship between XRCC1 Arg399Gln polymorphism and glioma risk. We searched the PubMed, EMBASE, and Web of Science and extracted 12 eligible studies with 4,062 glioma cases and 5,302 glioma-free controls for this meta-analysis. The pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to assess the strength of the association. In the overall analysis, we found that the XRCC1 Arg399Gln polymorphism was statistically associated with the risk of glioma (OR_{GG vs. AG + AA}?=?0.90, 95 % CI?=?0.84–0.97, P _{heterogeneity}?=?0.020; OR_{allele G vs. allele A}?=?0.96, 95 % CI?=?0.91–1.00, P _{heterogeneity}?=?0.110). We also observed significant association between this polymorphism and glioma risk in Asian populations. The results of the meta-analysis suggest a potential decreased susceptibility to glioma in association with the XRCC1 Arg399Gln polymorphism, especially in Asians. Yet, it is necessary to conduct future prospective explorations to gain a better insight into the impact of XRCC1 Arg399Gln polymorphism on glioma risk.     

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。     

XRCC1 Arg399Gln Gene Polymorphism and Hepatocellular Carcinoma Risk in the Chinese Han Population: A Meta-analysis

Purpose: Numerous studies have evaluated the association between XRCC1 Arg399Gln gene polymorphismand hepatocellular carcinoma risk in the Chinese Han population. However, the results have been inconsistent.We therefore here examined whether the XRCC1 Arg399Gln gene polymorphism confers hepatocellularcarcinoma risk by conducting a meta-analysis. Methods: PubMed, Google scholar and China National KnowledgeInfrastructure databases were searched for eligible articles in English and Chinese that were published beforeApril 2012. Results: 6 studies involving 1,246 patients with hepatocellular carcinoma and 1,953 controls wereincluded. The association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma inthe Chinese Han population was significant under GG vs AA (OR = 1.48, 95% CI = 1.13 to 1.94). Limiting theanalysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust.Conclusions: In the Chinese Han population, the XRCC1 Arg399Gln gene polymorphism is associated with anincreased hepatocellular carcinoma risk.     

Contribution of XPD (Lys751Gln) and XRCC1 (Arg399Gln) Polymorphisms in Familial and Sporadic Breast Cancer Predisposition and Survival: An Indian Report

The etiology of a significant proportion of familial breast cancers is still poorly understood, with known high penetrance gene mutations accounting for only a small proportion of the cases. The increased risk of breast cancer for the majority of women with a family history likely reflects shared minor low penetrant genetic factors. In the present case-control study undertaken to examine the influence of DNA damage repair gene polymorphisms in familial and sporadic breast cancer susceptibility, 219 Sporadic and 140 familial breast cancer patients and 367 controls were genotyped using PCRRFLP. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were calculated by unconditional logistic regression adjusted to age. Variant genotypes XRCC1 Arg/Gln or Gln/Gln and XPD Lys/Gln or Gln/Gln increased both familial and sporadic breast cancer susceptibility. However, when the intra group risk was compared, the risk due to the XPD polymorphic genotypes Lys/Gln or Gln/Gln was significantly lower among familial breast cancer patients compared to sporadic breast cancer patients [OR = 0.61; 95%CI = 0.39–0.94; p value = 0.024) whereas the risk implied by XRCC1 variant genotype was not significantly different between the familial and nonfamilial groups of breast cancer patients [OR = 0.97; 95%CI = 0.63–1.49; p value = 0.882]. Both these variant genotypes were not associated with the disease characteristics or survival of either familial or sporadic breast cancer patients. This study represents an addition to previous published work on GSTs from the same study population and substantiates the hypothesis that the impact of the low penetrance gene polymorphisms differ by family history of the disease.     

Arg399Gln XRCC1 Polymorphism and Risk of Squamous Cell Carcinoma of the Head and Neck in Jordanian Patients

Background and objective: X-ray repair cross-complementing group1 (XRCC1) is a key protein in base excision repair and closely associated with the coordination of the base excision repair pathway. Many studies have focused on XRCC1 SNPs and have shown an associated between these SNPs and the risk of several types of cancers, including head and neck cancer. There are many single nucleotide polymorphisms XRCC1 gene (SNPs) and the most common SNP that result in amino acid substitutions is exon 10 (Arg399Gln). This study aimed to investigate the association between Arg399Gln SNP and the risk of squamous cell carcinoma of the head and neck. Material and method: Ninety nine patients with squamous cell carcinomas of the head and neck and 89 healthy adult controls were enrolled in this study. The Arg399Gln in XRCC1 allele was genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Results: In the single-locus analyses, Arg399Gln SNP showed a significant association with head and neck cancer risk (p value = 0.016 and odd ratio of 1.8). On the genotype level, we applied three analysis models, namely co-dominant, dominant, and recessive genotypes. Arg/Arg homozygous major genotype was significantly (p value <0.05) associated with head and neck squamous cell carcinoma incidence with odd ratio of 2.23 and 2.24 for the co-dominant and recessive models, respectively. Conclusion: The findings indicated that Arg399Gln allele was associated with squamous cell carcinoma of the head and neck among Jordanian patients. This allele might be used as a genetic biomarker of squamous cell carcinoma of the head and neck.     

Assessment of the association between XRCC1 Arg399Gln polymorphism and lung cancer in Chinese

X-ray repair cross-complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base excision repair and plays an important role in the maintenance of genomic integrity. Polymorphisms in XRCC1 may alter the function and repair capacity of XRCC1 protein which further results in the genetic instability and lung carcinogenesis. Previous studies investigating the relationship between XRCC1 Arg399Gln polymorphism and lung cancer risk in Chinese yielded contradictory results. A meta-analysis was performed to clarify the effect of XRCC1 Arg399Gln polymorphism on lung cancer. The association was assessed by calculating the pooled odds ratio (OR) with 95 % confidence intervals (95 %CI). Nineteen studies with a total of 12,835 participants were included into this meta-analysis. Overall, there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models (Gln vs. Arg: OR?=?1.13, 95 %CI 1.01–1.25, P?=?0.029; GlnGln vs. ArArg: OR?=?1.41, 95 %CI 1.07–1.84, P?=?0.013; GlnGln vs. ArArg/ArgGln: OR?=?1.37, 95 %CI 1.07–1.76, P?=?0.013). Meta-analysis of 18 studies with high quality also found that there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models. There was no obvious risk of bias in the meta-analysis. Data from the current meta-analysis support the obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer in Chinese.     

Prospective assessment of XPD Lys751Gln and XRCC1 Arg399Gln single nucleotide polymorphisms in lung cancer.

PURPOSE: XRCC1 and XPD play key roles in the repair of DNA lesions and adducts. Contrasting findings have been reported on the effect of polymorphisms of these genes on the response to platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC). This study aimed to investigate the relationship between the XPD Lys751Gln and XRCC1 Arg399Gln genotypes and outcome in lung cancer patients. EXPERIMENTAL DESIGN: We genotyped 203 NSCLC and 45 small-cell lung carcinoma (SCLC) patients for the two polymorphisms. Most of the patients (81%) received a platinum-based chemotherapy. RESULTS: The patients' genotype frequencies did not significantly differ from controls and both groups were in Hardy-Weinberg equilibrium for the two polymorphisms. The XRCC1399 Gln/Gln variant genotype was associated with a higher median survival time (80 weeks versus 54.6 weeks for the Arg/Gln heterozygous and 55.6 weeks for the wild-type Arg/Arg genotype; P=0.09). At the multivariable analysis adjusted for histology, stage of the disease, performance status, age, and gender, the Gln/Gln genotype was associated with a better survival of borderline significance in the subgroup of patients treated with cisplatin (hazard ratio, 0.55; 95% CI, 0.30-1.00); this association became significant for those with grade 3-4 clinical toxicity (hazard ratio, 0.46; 95% CI, 0.22-0.98). No association between XPD Lys751Gln genotype and clinical outcome was found. CONCLUSION: This prospective investigation provides suggestive evidence of a favorable effect of the XRCC1399 Gln/Gln genotype on survival in platinum-treated NSCLC and, for the first time, in SCLC patients also. This contrasts with other authors who did not include non-platinum-treated patients, but it does fit the expectation for a suboptimal ability to remove DNA adducts.     

XRCC1基因Arg399Gln多态与胃癌临床病理因素的关系

背景与目的：DNA修复基因XRCC1参与DNA损伤的碱基切除修复途径（BER），其Arg399Gln多态可以改变蛋白产物的DNA修复效能．本研究探讨XRCC1基因Arg399Gln多态与胃癌临床病理因素的关联性。方法：采用聚合酶链反应PCR-变性高效液相色谱分析（denaturing high performance liquid chromatography，DHPLC）方法对102例胃癌患者进行XRCC1基因Arg399Gln多态的基因型分析，比较基因型分布与胃癌组织临床病理特征之间的关系。结果：XRCC1基因Arg399Gln多态的Arg／Arg（GG），Arg／Gin（G→A）及Gin／Gin（AA）基因型在病例组中的分布频率分别为46（45．1％），48（47．1％），8（7．8％）；含至少一个399Gln的基因型患胃癌的年龄明显要小（P=0．07）；Arg399Gln多态性与胃癌的病理类型、肿瘤部位、组织分级、浸润深度及淋巴结转移、临床分期间没有显著关系（P〉0．05）。结论：XRCC1基因399Gln等位基因可能是胃癌早年发病的危险因素之一；但不是判断胃癌侵袭相关的生物学行为的预测指标。这些结果还需要大样本量的胃癌分子流行病学研究加以验证。