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.     

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.     

Polymorphism of the DNA Repair Gene XRCC1 (Arg194Trp) and its role in Colorectal Cancer in Kashmiri Population: a Case Control Study

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNArepair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importanceof mutations in mismatch repair genes has been extensively documented. Materials and Methods: In this studywe focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair(BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the roleof XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. Results:Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP)method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant(p < 0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp)being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95%CI=1.42-19.5)] respectively. Conclusions: Our results suggest an increased risk for CRC in individuals withXRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectalcancer in the Kashmiri population.     

XRCC1 and XPD Gene Polymorphisms in a South Indian Population

DNA repair systems play an important role in maintaining the integrity of the human genome. Deficiency inthe repair capacity due to either mutations or inherited polymorphisms in DNA repair genes may contribute tovariations in the DNA repair capacity and subsequently susceptibility to cancer. The interindividual variabilityas well as ethnic differences in DNA repair polymorphisms, stress the importance to establish genotype profilesunique to a population. Hence the present study aimed to determine the frequencies of XRCC1 and XPD genepolymorphisms in 255 healthy random unrelated individuals from South India. DNA was isolated from theperipheral blood sample of these individuals and the XRCC1 and XPD genotypes were determined by PCRRFLPwith Msp1 and Pst1 enzymes respectively. The XRCC1 genotype frequencies revealed 36% Arg/Arg,47% Arg/Gln and 17% Gln/Gln with Gln allele frequency of 0.41. Analysis of XPD genotypes revealed 51% Lys/Lys, 41% Lys/Gln and 8% Gln/Gln with Gln allele frequency of 0.29. No significant difference in the distributionof genotypes was seen based on gender. Comparison of the frequencies of XRCC1 and XPD polymorphismsobserved in the present study with other populations revealed a distinctive nature of the South Indian population.An understanding of DNA repair gene polymorphisms might not only enable risk assessment of humans exposedto environmental carcinogens but also response to therapy, which target the DNA repair pathway.     

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.     

Polymorphism of DNA repair gene XRCC1 and hepatocellular carcinoma risk in Chinese population

Aim: We conducted a case-control study in China to clarify the association between the XRCC1-Arg399Gln polymorphism and HCC risk. Methods: A total of 202 cases and 236 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. Assessment of the XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method. All analyses were performed using the STATA statistical package. Results: A significant increase in risk was associated with the Arg/Gln genotype (adjusted OR 1.55, 95%CI=1.03-2.57) compared with Arg/Arg. However, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.34(0.67-2.38). There was also a significant increasewith the Arg/Gln genotype among HCC patients above 50 years old (OR=1.95, 95% CI=1.14-3.57). Additionally, the risk of HCC was moderately increased in drinkers with Arg/Gln genotype compared with never drinkers, and the adjusted OR (95% CI) was 1.89 (1.13-3.45). Conclusion: This study demonstrated that a polymorphism in a DNA repair gene may influence the risk of HCC. The XRCC1 codon Arg/Gln was thuis associated with an increased risk of HCC, especiallyin patients above 50 years old and/or with a drinking habit.     

XRCC1基因多态性与膀胱癌关系的病例对照研究

[目的]探讨人类DNA修复基因XRCC1 Arg194Trp单核苷酸多态性与膀胱癌危险性的关系。[方法]采用PCR-RFLP分析技术检测242例膀胱癌患者及225例人群对照XRCC1基因194位点的多态性。应用非条件Logistic回归模型，调整混杂因素后，分析各基因型与膀胱癌发生的关系以及是否与吸烟因素存在着交互作用。[结果]膀胱癌病例组的194Trp／Trp突变基因型频率（11.2％）显著高于对照组（4．0％）。调整年龄、性别、吸炯、高危职业史、膀胱感染和体质指数等因素后，携带194Trp/Trp基因型个体患膀胱癌的风险是194Arg／Arg基因型个体的3．64倍（95％CI：1．60～8．30）。此基因型与吸娴对增加膀胱癌发病风险无明显交互作用。去除了吸烟的混杂效应后，194Trp／Trp基因型个体患膀胱癌的危险性是其它基因型个体的3．16倍（95％CI：1．45～6．88）。[结论]XRCC1基因194Trp／Trp突变基因型增加膀胱癌发病风险，与吸烟无交互作用。     

XRCC1单核苷酸多态性与鼻咽癌铂类化疗敏感度的相关性

目的 探讨鼻咽癌铂类化疗敏感度与X射线交错互补修复基因1 codon194和codon399单核苷酸多态性的相关性。方法 收集广西医科大学第四附属医院2012年9月1日至2013年12月31日鼻咽部肿物活检确诊为鼻咽癌患者资料,采用限制性片段长度多态性聚合酶链反应技术检测鼻咽癌患者外周血DNA XRCC1 codon194和codon399单核苷酸多态性。顺铂+氟尿嘧啶方案诱导化疗2周期后复查MRI,按照RECIST 1.1标准评价其化疗敏感度,分析单核苷酸多态性（Single nucleotide polymorphism,SNP）与化疗敏感度的关系。结果 XRCC1 codon399 Gln/Gln基因型携带者化疗敏感度为Arg/Arg基因型携带者的3.500倍（P＜0.05）。XRCC1 codon399不含Arg基因型（即Gln/Gln）携带者化疗敏感度为含Arg基因型（Arg/Arg 和 Arg/Gln）携带者的3.274倍,（P＜0.05）。携带XRCC1 codon194各基因型患者化疗敏感度之间差异无明显统计学意义（P＞0.05）。结论 XRCC1 codon399 单核苷酸多态性有可能成为鼻咽癌铂类化疗敏感度的预测因子。     

Association between the NQO1 C609T Polymorphism with Hepatocellular Carcinoma Risk in the Chinese Population

Background: Associations between the NQO1 C609T polymorphism and hepatocellular carcinoma (HCC)risk are a subject of debate. We therefore performed the present meta-analysis to evaluate links with HCCsusceptibility. Materials and Methods: Several major databases (PubMed, EBSCO), the Chinese nationalknowledge infrastructure (CNKI) and the Wanfang database were searched for eligible studies. Crude odds ratios(ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations. Results: A total of4 studies including 1,325 patients and 1,367 controls were identified. There was a significant association betweenNQO1 C609T polymorphism and HCC for all genetic models (allelic model: OR=1.45, 95%CI=1.23-1.72, p<0.01;additive model: OR=1.96, 95%CI=1.57-2.43, p<0.01; dominant model: OR=1.62, 95%CI=1.38-1.91, p<0.01; andrecessive model: OR=1.53, 95%CI=1.26-1.84, p<0.01). On subgroup analysis, similarly results were identified inAsians. For Asians, the combined ORs and 95% CIs were (allelic model: OR=1.50, 95%CI=1.24-1.82, p<0.01;additive model: OR=2.11, 95%CI=1.48-3.01, p<0.01; dominant model: OR=1.69, 95%CI=1.42-2.02, p<0.01;and recessive model: OR=1.59, 95%CI=1.16-2.19, p<0.01). Conclusions: The current meta-analysis suggestedthat the NQO1 C609T polymorphism could be a risk factor for developing HCC, particularly in the Chinesepopulation.     

DNA修复基因XRCC1在宫颈癌中的表达

目的　探讨DNA修复基因XRCC1在宫颈癌组织中的表达及其临床意义。方法　应用免疫组织化学SP法 ,检测 10例正常宫颈 ,60例宫颈鳞癌和 9例宫颈腺癌组织中XRCC1的表达水平。结果　在宫颈癌组织中XRCC1的阳性表达率为 66 7% (4 6/67) ;与正常宫颈组织中比较 ,有显著差异 (P <0 0 5 ) ;XRCC1在宫颈癌中的表达与临床分期及组织学分级有关 (P <0 0 1) ,与淋巴结转移和病理类型无关 (P >0 0 5 )。结论　DNA修复基因XRCC1与宫颈癌的发生发展密切相关。     

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。     

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.     

Relationship Between GSTT1 Gene Polymorphism and Hepatocellular Carcinoma in Patients from China

Objective: The results from studies on associations of the glutathione S-transferase T1 (GSTT1) genepolymorphism and hepatocellular carcinoma (HCC) risk in Chinese populations are still conflicting. This metaanalysiswas performed to evaluate the relationship in detail. Methods: Eligible reports were recruited into thismeta-analysis from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China BiologicalMedicine Database). Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidenceintervals (CI) were also calculated. Results: Eighteen investigations were identified for the analysis of associationbetween polymorphic deletion of GSTT1 and HCC, consisting of 2,693 patients with HCC and 4,696 controls.Null genotype of GSTT1 was associated with HCC susceptibility in Chinese (OR=1.53, 95%CI: 1.28-1.82;P﹤0.00001). Conclusion: The GSTT1 null genotype is associated with HCC susceptibility in Chinese.     

XRCC1 Gene Polymorphism,Diet and Risk of Colorectal Cancer in Thailand

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. This study aimed to investigate the interaction between the presence of a polymorphism of the XRCC1 gene and known risk factors for colorectal cancer in Thailand. Materials and Methods: A hospital-based case-control study was conducted in Thailand. The participants were 230 histologically confirmed new cases and 230 controls matched by sex and age and recruited from the same hospital. Information about demographic characteristics, life style, anddietary habits was collected using structured interviews, and blood samples were taken which were used for the detection of a homozygous and heterozygous polymorphisms of XRCC1. Associations were assessed using multiple conditional logistic regression. Results: In the univariate analysis, factors found to be significantly associated with an increased risk for CRC were the presence of the XRCC1 AA homozygote (OR= 4.95; 95% CI: 1.99-12.3), a first degree family history of cancer (OR= 1.74; 95% CI: 1.18-2.58), and a high frequency ofpork consumption (OR= 1.49; 95% CI: 1.00-2.21). Intakes of fish fruit and vegetables appeared to be protective factors, but the associations were not statistically significant. In the multivariate analysis only the XRCC1 AAhomozygote polymorphism and a family history of cancer emerged as risk factors (OR= 4.96; 95% CI: 1.90-12.95 and OR=1.80; 95% CI: 1.18-2.72, respectively). Conclusions: While the XRCC1 AA homozygote and a family history of cancer were found to be associated with an increased risk of CRC, none of the dietary intake variables were clearly identified as risk or protective factors. There is a need for further research to determine the reasons for this.     

GSTM1基因多态现象与原发性肝癌遗传易感性的关系研究

目的探讨谷胱甘肽Ｓ转移酶Ｍ１（ＧＳＴＭ１）基因多态现象与原发性肝癌遗传易感性的关系。方法应用多重ＰＣＲ方法检测５４例肝癌患者（病例组）和１３６例健康人（对照组）的ＧＳＴＭ１空白基因型。结果病例组ＧＳＴＭ１空白基因型频率为７０．３７％，对照组则为４５．５９％，两者非常显著性差异（Ｐ〈０．０１），但２组均不存在性别，年龄差异（Ｐ均〉０．０５）；ＯＲ值为２．８３（９５％ＣＩ值为１．４３－５．４２），ＥＦ     

The XRCC1 Arg399Gln Genetic Polymorphism Contributes to Hepatocellular Carcinoma Susceptibility: An Updated Metaanalysis

The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphismwith hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results ofprevious meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-controldatasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixedeffectmodel or a random-effect model, depending on between-study heterogeneity, were applied to estimatethe association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as oddsratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as wellas in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively),but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A,OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A,OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, nopotential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups wasidentified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphismcontributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample andrigorous studies are needed to validate the findings.     

DNA Repair Gene Polymorphisms at XRCC1, XRCC3, XPD,and OGG1 Loci in the Hyderabad Population of India

Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inherited SNPs of DNA repair genes may contribute to variation in DNA repair capacity and susceptibility to cancer. Due to thepresence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. India harbors enormous genetic and cultural diversity. Materials and Methods: In the present study we aimed to determine the genotypes and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 186 healthy individuals residing in the Hyderabad region of India and to compare them with HapMap and otherpopulations. Results and Conclusions: The genotype and allele frequency distribution at the four DNA repairgene loci among Hyderabad population of India revealed a characteristic pattern. Comparison of these genepolymorphisms with other populations revealed a distinctiveness of Hyderabad population from the Deccanregion of India. To the best of our knowledge, this is the first report of such DNA repair gene polymorphisms inthe Deccan Indian population.     

中国人DNA修复基因XRCC1单核苷酸多态及其与食管癌风险的关系

目的：研究碱基切除修复基因ＸＲＣＣ１单核苷酸多态与食管癌易感性的关系。方法：以ＰＣＲ－ＲＦＬＰ方法分析了食管癌病例（ ｎ＝２２２）和按性别、年龄频数配对的正常对照者（ ｎ＝４３３） ＸＲＣＣ１基因 Ｃ２６３０４Ｔ和 Ｇ２８１５２Ａ多态,并比较不同基因型与食管癌风险的关系以及基因多态与吸烟之间的交互作用对食管癌风险的影响。结果：在食管癌病人中ＸＲＣＣ１　２６３０４ＴＴ变异基因型频率为１２．６％,高于对照组的６．７％（Ｐ＜０．０５）;携带此种基因型个体发生食管癌的风险比携带其他基因型者高１． ８倍（校正的ＯＲ＝１．８３, ９５％ ＣＩ　１．０３～３．２４）。Ｇ２８１５２Ａ基因型频率在对照组和病例组中的分布无显著性差异（Ｐ＞０．０５）,因而与食管癌风险无关。ＸＲＣＣ１基因这两个位点多态之间没有联合作用,但２６３０４ＴＴ基因型与吸烟之间有一定的协同作用,在吸烟与否和吸烟量两个层次,２６３０４ＴＴ基因型均与之有联合作用而增高食管癌风险。结论：ＤＮＡ碱基切除修复基因ＸＲＣＣ１多态可能在食管癌的发生过程中起一定作用。     

肝细胞癌、鼻咽癌患者谷胱甘肽硫转移酶M1和T1基因型分布

目的 探讨高危区肝细胞癌和鼻咽癌患者谷胱甘肽硫转移酶M1 (GSTM1) 及T1 (GSTT1)基因多态性的分布。方法 应用PCR技术检测181例肝细胞癌、126例鼻咽癌患者和641例对照组人体GSTM1和GSTT1基因型。结果 GSTM1空白基因型(null)在肝癌组、鼻咽癌组与对照组频率分别为65.2%、61.9%和47.6%,病例组与对照组比较,差异有统计学意义（P＜0.01)。GSTT1空白基因型(null)在肝癌组、鼻咽癌组与对照组频率分别为57.5%、62.7%和43.1%,病例组与对照组比较,差异有统计学意义（P＜0.001)。结论 在肝细胞癌、鼻咽癌高发区解毒酶基因GSTM1和GSTT1呈多态性分布,二者的null基因型均增加患肝细胞癌、鼻咽癌的风险。     

Polymorphisms of XRCC1 and XRCC2 DNA Repair Genes and Interaction with Environmental Factors Influence the Risk of Nasopharyngeal Carcinoma in Northeast India

Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One-hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The XRCC1 Gln/Gln genotype showed increased risk (OR=2.76; P<0.024) of NPC. However, individuals with both XRCC1 and XRCC2 polymorphic variants had 3.2 fold elevated risk (P<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying XRCC1 polymorphic variants. However, smokers carrying defective XRCC1 gene showed the highest risk (OR = 7.47; P<0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of XRCC1 variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; P<0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with XRCC1. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations.