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.     

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。     

An updated meta-analysis between the association of XRCC1 Arg399Gln polymorphism and hepatocellular carcinoma risk

Background: Various studies have evaluated the relationship between X-ray repair cross-complementinggroup 1 (XRCC1) Arg399Gln polymorphism and hepatocellular carcinoma (HCC) risk, but the conclusionshave been inconsistent and underpowered. The purpose of this updated meta-analysis was to examine whetherXRCC1 Arg399Gln polymorphism confers susceptibility to HCC. Methods: Eligible studies extracted fromPubMed, Embase, Cochrane Library, VIP (chinese) and CNKI (chinese) up to November 2013 were included inthe study. Pooled odds ratio (OR) together with their 95% confidence interval (CI) were estimated to evaluateXRCC1 Arg399Gln polymorphism and HCC risk. Results: Finally, 21 studies with 4,170 cases and 5,030controls were involved in our meta-analysis. The results demonstrated that there was significant associationbetween Arg399Gln polymorphism and HCC risk under two contrast models in overall populations (AG vs GG:OR=1.265, 95%CI=1.036-1.545, p=0.021; AA+AG vs GG: OR=1.240, 95%CI=1.021-1.506, p=0.030). In subgroupanalyses, significant association was found in Asians (A vs G: OR=1.175, 95%CI=1.013-1.362, p=0.033; AG vsGG: OR=1.317, 95%CI=1.070-1.622, p=0.009; AA+AG vs GG: OR=1.289, 95%CI=1.055-1.575, p=0.013) andCaucasians (A vs G: OR=0.591, 95%CI=0.361-0.966, p=0.036; AA+AG vs GG: OR=0.468, 95%CI=0.234-0.934,p=0.031). Conclusions: The results suggest that XRCC1 Arg399Gln polymorphism may increase HCC riskespecially among Asians. However, XRCC1 Arg399Gln polymorphism might act as a protective role againstHCC among Caucasians.     

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.     

DNA修复基因XRCC1的399位点多态性同肺癌易感性关系的Meta分析

目的综合评价DNA修复基因XRCC1(X-raycross-complementinggroup1)的399位点多态性同肺癌易感性的关系。方法检索中国生物医学数据库和Medline,获得有关XRCC1基因399位点多态性同肺癌易感性关系的研究结果,并进行Meta分析。所有文献均采用病例对照研究,以非条件Logistic回归校正年龄、性别和吸烟状况等混杂因素后的OR值为效应指标,对文献进行评价筛选、异质性检验。利用Meta分析软件RevMan4·2对各研究原始结果进行统计处理,并计算合并OR值及其95%可信区间。结果本次Meta分析共纳入15项研究,累计病例6818例,对照7610例。Arg/Gln和Gln/Gln等位基因同Arg/Arg比较,OR值分别为0·99(95%CI0·91~1·06)和1·04(95%CI0·92~1·17),Z值分别为-0·37和0·67,对应的P值分别为0·71和0·50。结论尚无足够证据证明DNA修复基因XRCC1的399位点多态性同肺癌易感性有关。     

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。     

Association between XRCC1 Arg399Gln polymorphism and hepatitis virus-related hepatocellular carcinoma risk in Asian population

To investigate the association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and hepatitis virus-related hepatocellular carcinoma risk, we performed a systematic meta-analysis of eligible case–control studies. Eligible studies were identified from the PubMed, Embase, and Chinese National Knowledge Infrastructure databases up to March 2013. The odds ratios (ORs) and corresponding 95 % confidence interval (95 % CI) of XRCC1 Arg399Gln polymorphism in hepatitis virus-related hepatocellular carcinoma cases compared with those in controls were calculated. The meta-analysis was performed using fixed-effect or random-effect methods according to the absence or presence of heterogeneity. This meta-analysis included 1,558 cases with hepatitis virus-related hepatocellular carcinoma and 1,338 controls. Meta-analysis of available data showed that there was no association between XRCC1 Arg399Gln polymorphism and risk of hepatitis virus-related hepatocellular carcinoma under all contrast models (Gln vs. Arg: fixed-effect OR?=?0.92, 95 % CI 0.82–1.04, P?=?0.18; GlnGln vs. ArgArg: random-effect OR?=?0.79, 95 % CI 0.50–1.25, P?=?0.32; GlnGln/ArgGln vs. ArgArg: fixed-effect OR?=?0.92, 95 % CI 0.79–1.07, P?=?0.28; and GlnGln vs. ArgArg/ArgGln: random-effect OR?=?0.83, 95 % CI 0.52–1.34, P?=?0.45). Sensitivity analysis further showed that there was no association between XRCC1 Arg399Gln polymorphism and risk of hepatitis B-related hepatocellular carcinoma under all contrast models (Gln vs. Arg: fixed-effect OR?=?0.93, 95 % CI 0.82–1.05, P?=?0.25; GlnGln vs. ArgArg: fixed-effect OR?=?0.86, 95 % CI 0.64–1.16, P?=?0.32; GlnGln/ArgGln vs. ArgArg: fixed-effect OR?=?0.93, 95 % CI 0.80–1.10, P?=?0.41; and GlnGln vs. ArgArg/ArgGln: fixed-effect OR?=?0.85, 95 % CI 0.63–1.13, P?=?0.26). Our meta-analysis of the available data did not find an obvious effect of XRCC1 Arg399Gln polymorphism on hepatitis-related hepatocellular carcinoma. More well-designed studies with large sample are needed to further verify the effect.     

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.     

A population-based case-control study of the XRCC1 Arg399Gln polymorphism and susceptibility to bladder cancer.

Cigarette smoking is the major cause of bladder cancer. Constituents in tobacco smoke can induce oxidative DNA damage requiring base excision repair. The Arg399Gln polymorphism in the DNA base excision repair gene XRCC1 is associated with several phenotypic markers of reduced DNA repair capacity. Results from several epidemiologic studies suggest that the Arg399Gln polymorphism may influence susceptibility to several cancers including bladder cancer; however, data from large population-based studies are lacking. In a population-based case-control study from New Hampshire, we observed a reduced risk among those homozygous for the Arg399Gln XRCC1 variant polymorphism compared with those with one or two wild-type alleles (odds ratio 0.6, 95% confidence interval 0.4-1.0). There was no indication of a gene-environment interaction between cigarette smoking and the variant genotype. Our data are consistent with a potential role of the XRCC1 Arg399Gln polymorphism in bladder cancer susceptibility and further suggest that there may be DNA lesions important in bladder carcinogenesis, repaired by the base excision repair mechanism, that are not directly associated with tobacco smoking.     

XRCC1 Arg399Gln gene polymorphism and breast cancer risk: a meta-analysis based on case-control studies

Background: The Arg399Gln polymorphism in the XRCC1 DNA repair gene is likely to be involved with the development of breast cancer (BC). However, there have been inconsistent reports of association. The objective of this study was to systematically evaluate the published papers. Methods: We performed a meta-analysis of 44 published case-control studies fitting our eligibility criteria. These studies involved XRCC1 Arg399Gln polymorphisms in 20,841 BC cases and 22,688 controls in dominant (GlnGln+ArgGln vs. ArgArg), recessive (GlnGln vs. ArgGln+ArgArg), and co-dominant (GlnGln vs. ArgArg) inheritance models. Analyses of Asian, African and Caucasian ethnic subgroups was also conducted. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Results: Our overall analyses indicated Arg399Gln to be associated with a trend of increased BC risk when using recessive (OR=1.15, 95%CI: 1.05–1.27), and co-dominant models (OR=1.15, 95%CI: 1.04-1.27) to analyze the data. In ethnic subgroups, Arg399Gln significantly increased BC risk in Asians (OR=1.54, 95%CI: 1.18–2.01) when using recessive model analysis, in Africans (OR=1.30, 95%CI: 1.07–1.60) when using dominant model analysis, and in Asians (OR=1.50, 95%CI: 1.15–1.97) and Africans (OR=1.80, 95%CI: 1.08-3.02) when using the co-dominant model analysis. Conclusions: From our meta-analysis of data from 44 publications, we conclude that XRCC1 Arg399Gln allele is a risk factor for the development breast cancer, especially among Asian and African populations.     

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 Arg399Gln polymorphism is not associated with oral cancer risk: evidence from a meta-analysis

Previous studies regarding the association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and oral cancer risk were contradictory. We performed a meta-analysis to derive a more precise estimation of the association. The PubMed and Web of Science were searched for eligible studies. Odds ratio (OR) with its 95 % confidence interval (95 % CIs) was used to assess the strength of the association. Nine individual studies with a total of 3,244 subjects were finally included into the meta-analysis. Overall, there was no association between XRCC1 Arg399Gln polymorphism and oral cancer risk under all genetic models (Gln versus Arg: OR?=?1.09, 95 % CI 0.86–1.37, P?=?0.46; GlnGln versus ArgArg: OR?=?1.11, 95 % CI 0.69–1.79, P?=?0.66; GlnGln versus ArgArg/ArgGln: OR?=?1.04, 95 % CI 0.68–1.61, P?=?0.84; and GlnGln/ArgGln versus ArgArg: OR?=?1.13, 95 % CI 0.88–1.44, P?=?0.34). After excluding studies on oral leukoplakia, there was still no association between XRCC1 Arg399Gln polymorphism and oral cancer risk under all genetic models. Subgroup analysis by ethnicity suggested that there was no association between XRCC1 Arg399Gln polymorphism and oral cancer risk in both Asians and Caucasians. In conclusion, the data from the meta-analysis suggests that XRCC1 Arg399Gln polymorphism is not associated with oral cancer risk.     

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.     

A population-based case-control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer.

XRCC1 (X-ray repair cross-complementing group 1) is a base excision repair protein that plays a central role in the repair of DNA base damage and strand breaks. A common polymorphism (Arg-->Gln) at codon 399 of the XRCC1 gene has been previously linked to functional changes of the gene product and risk of cancers. We evaluated the association between XRCC1 Arg399Gln polymorphism and breast cancer risk in the population-based Shanghai Breast Cancer Study involving 1088 cancer patients and 1182 community controls. Genomic DNA from peripheral blood was used in genotyping assays, and exposure information and anthropometrics were collected through in-person interview. Plasma estrogen and sex hormone-binding globulin (SHBG) levels were measured for 190 postmenopausal breast cancer patients who had donated a pretreatment blood sample and 407 postmenopausal controls. Conditional logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusting potential confounders. Approximately 27% of controls carried the variant allele (Gln), and cases and controls had a similar distribution for both allele type and genotype of this polymorphism. We found that 7.8% of cases and 6.3% of controls were homozygous for the variant allele, resulting in an OR of 1.20 (95% CI, 0.85-1.69). The OR was slightly higher among younger women [<45 years of age (OR, 1.39; 95% CI, 0.82-2.36)] than older women [> or = 45 years of age (OR, 1.07; 95% CI, 0.68-1.67)], but neither OR was statistically significant. No modifying effect of major breast cancer risk factors, including years of menstruation, body mass index, waist:hip ratio, and blood estrogen levels, was noted. Homozygosity for the variant Gln allele was associated with an elevated risk of postmenopausal breast cancer among subjects with a higher blood level of SHBG (OR, 3.27; 95% CI, 1.16-9.20) and a reduced risk among those with a lower level of SHBG (OR, 0.60; 95% CI, 0.18-1.97). The overall results of the study suggest that Arg399Gln polymorphism of the XRCC1 gene alone may not play a substantial role in the risk of breast cancer among Chinese women.     

The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction.

XRCC1, a protein directly involved in the repair of DNA base damage, contains at least three common polymorphisms. One of these, the codon 399 arg-->gln variant, has been associated with several cancer-related biomarkers, suggesting it may have functional significance in exposure-induced cancers. However, results from case-control studies have yielded conflicting results. We investigated the XRCC1 arg399gln polymorphism and its interaction with carcinogen exposure in a large, population-based case-control study of non-melanoma skin cancer. Cases were derived from an incident survey of all newly diagnosed non-melanoma skin cancer in New Hampshire, and controls were population based and frequency matched to cases on age and sex (n = 1176). Exposure information was derived from a detailed interviewer-administered questionnaire, and XRCC1 genotype was determined from blood-derived DNA using a PCR-RFLP method. Overall, the XRCC1 homozygous variant gln399gln genotype was related to a significantly reduced risk of both basal cell [BCC; odds ratio (OR) 0.7, 95% confidence interval 0.4-1.0] and squamous cell carcinoma (SCC; OR 0.6, 95% confidence interval 0.3-0.9). There was no significant gene-environment interaction of the variant XRCC1 genotype and a history of therapeutic X-ray exposure. However, there was a statistically significant multiplicative interaction of XRCC1 genotype and lifetime number of sunburns in SCC [likelihood ratio test (2 d.f.), P < 0.02]. Although the absolute risk of SCC associated with sunburns was similar across genotypes, the relative risk of SCC associated with painful sunburn history was significantly higher for homozygous variants than wild types (OR 6.8 for gln399gln and 1.5 for arg399arg). In summary, our data show that the homozygous XRCC1 variant (gln399gln) is associated with a lower risk of non-melanoma skin cancer and suggest that the etiology of sunburn-related SCC may be significantly different by XRCC1 genotype. These data, using the classic skin carcinogenesis model, provide new insight on the role of the XRCC1 399 polymorphism in neoplasia and may help explain the conflicting results relating this polymorphism to cancer risk at various sites.     

广西扶绥县肝癌家系XRCC1基因Arg399Gln多态性与肝细胞癌的遗传易感性

目的研究广西扶绥县肝癌家系人群DNA修复基因XRCC1Arg399Gln多态性与肝细胞癌（HCC）遗传易感性的相关性。方法采用病例-对照研究方法,对扶绥县21个肝癌家系人群和10个正常家系人群,运用PCR-RFLP方法分析XRCC1基因Arg399Gln位点多态性,并应用Logistic回归模型分析该位点多态性与肝细胞癌遗传易感性的关系。结果通过XRCC1Arg399Gln基因型检测分型,肝癌家系人群携带变异等位基因Gln的频率为23.68%,正常家系人群为13.16%,等位基因在两组间的分布差异无统计学意义（P〉0.05）。基因型分布符合Hardy-Weinberg平衡定律。正常家系人群中携带Arg/Gln者发生HCC的风险是携带Arg/Arg者的1.622倍（95%CI=0.475～5.541,P=0.440）。肝癌家系人群中除肝癌患者外,携带Arg/Gln、Gln/Gln者发生HCC的风险分别是携带Arg/Arg者的1.198倍（95%CI=0.362～3.968）和2.964倍（95%CI=0.434～20.220,P分别为0.768、0.267）。结论广西扶绥县肝癌家系人群中,XRCC1399Arg/Gln基因型和Gln/Gln基因型者患HCC的风险较Arg/Arg基因型者有增加的趋势,但不存在显著相关性。     

XRCC 1 Arg399Gln基因多态性对铂类药物化疗胃癌患者预后的影响

目的：研究DNA修复酶X射线损伤交叉互补蛋白1（X-ray repair cross-complementary protein1，XRCCl）基因Arg399Gln多态性对接受铂类药物辅助化疗的胃癌患者预后的影响。方法：选取经病理学确诊的胃癌患者84例，采用含铂类药物的联合化疗方案进行辅助化疗。化疗前采集患者外周血，采用聚合酶链反应．连接酶检测反应（polymerase chain reaction-ligation detection reaction，PCR-LDR）技术检测XRCCl基因Arg399Gln的多态性。结果：84例胃癌患者中，49例（58．3％）携带XRCCl的399Axg／Arg基因型，30例（35．7％）携带Arg／Gln基因型，5例（6．0％）携带Gin／Gin基因型；截止到随访结束，分别有63．1％（53／84）和55．2％（43／84）的患者出现复发和死亡，其中携带Arg／Arg基因型的胃癌患者复发率和死亡率均显著低于携带Arg／Gln或Gln／Gln基因型患者（P〈0.05）。COX多因素分析显示，携带Arg／Arg基因型的患者具有较好的无复发生存期和总生存期预后（P〈0．05）。结论：XRCClArg399Gln基因多态性与术后胃癌患者接受铂类药物化疗后的预后有关，可以在一定程度上判断术后胃癌患者接受铂类药物化疗的预后情况。     

Association of XRCC1 genetic polymorphism (Arg399Gln) with laryngeal cancer: a meta-analysis based on 4,031 subjects

Several case–control studies on the relation between XRCC1 gene Arg399Gln polymorphism and laryngeal cancer do not have similar conclusions. To further evaluate the relation between the XRCC1 gene Arg399Gln polymorphism and laryngeal cancer, we selected seven case–control studies related to the XRCC1 gene Arg399Gln polymorphism and laryngeal cancer by searching MEDLINE, EMBase, Chinese Biomedical Literature Database, Chinese CNKI, and Wanfang database. We utilized Q test and I ² test to test the heterogeneity between each study. The fixed effects model was utilized to calculate the odds ratio (OR) and 95 % confidence interval. The present study included 1,654 patients with laryngeal cancer and 2,377 cancer-free control subjects. By meta-analysis, we did not find any association of XRCC1 gene Arg399Gln polymorphism with laryngeal cancer (OR?=?1.13, 95 % CI 0.81–1.58, P?=?0.47). Therefore, we concluded that XRCC1 gene Arg399Gln polymorphism was not associated with laryngeal cancer.