X射线损伤修复交叉互补基因1（XRCC1）单核苷酸多态性与神经胶质瘤易感性关系的meta分析

目的：采用meta 分析方法探讨X 射线损伤修复交叉互补基因1（XRCC1）单核苷酸多态性与神经胶质瘤易感性的关系。方法：研究检索了PubMed、EMBASE、ISI Web of sciences、ScienceDirect 及CNKI 数据库从建库至2012 年9 月关于XRCC1 基因多态性与神经胶质瘤相关性的相关文献。合并的OR 值及其95%CI用于评估不同基因模型与神经胶质瘤风险的关联强度。采用亚组分析和meta 回归分析来探索潜在的异质性来源。结果：研究最终纳入12 篇Arg399Gln、8 篇Arg194Trp 和5 篇Arg280HisXRCC1 位点多态性与神经胶质瘤关系文章用于meta 分析。Arg399Gln 位点多态性在所有基因模型下合并OR 值均有显著意义;Arg194Trp 位点多态性在纯合子基因模型和隐性基因模型下合并OR 值具有显著意义;未发现Arg280His 位点多态性与神经胶质瘤风险相关基因模型。亚组分析和meta 回归分析显示Arg399Gln 位点多态性的所有基因模型风险仅在亚洲人群当中具有显著意义,亚洲人群的风险显著高于白种人群。Arg194Trp对照组人群不符合Hardy-Weinberg平衡（HWE）可能高估了风险。结论：本研究结果显示XRCC1 Arg399Gln 基因多态性仅为亚洲人群的神经胶质瘤风险的候选基因,Arg194Trp 基因多态性的风险可能是由于对照组不符合HWE 的研究所导致的。     

单核细胞趋化蛋白-1基因多态性与癌易感性的Meta分析

探讨单核细胞趋化蛋白-1(MCP-1)2518 A/G基因多态性与癌易感性的关联情况。计算机检索相关数据库,收集自建库至2016年12月国内外已发表的有关MCP-1-2518 A/G基因多态性与肿瘤易感性关联的研究。共纳入30项病例对照研究(包括5 602例患癌患者和6 500例健康对照人群)。采用Stata 12.0软件进行统计学分析。Cochran Q检验和I2检验对各研究进行异质性检验,计算合并比值比(OR值)及其95%可信区间(95%CI)以评价关联性,Begg's test和Egger's test评估发表偏倚,并进行Meta回归、敏感性分析。Meta分析结果提示MCP-1-2518 A/G多态性与癌患病风险无明显相关性。但根据肿瘤类型的亚组分析发现,MCP-1基因多态性与肝癌、乳腺癌、卵巢癌和非小细胞肺癌的发病风险显著相关(p0.05)。根据种族进行的亚组分析发现,携GG基因型的白种人群患癌风险增加(GG vs.AG/AA:OR=1.81,95%CI=1.10~2.96),而MCP-1-2518 A/G多态性与亚洲人群患癌风险无相关性(p0.05)。多态性与癌易感性的关联在基于对照组来源、研究样本量和低质量研究的亚组分析中显著,而根据对照组是否符合HWE遗传平衡和基因检测方法的亚组分析,这种关系不显著。Meta回归分析表明,种族差异和纳入研究的质量可能是各研究间异质性存在的主要来源。综上所述,MCP-1-2518 A/G多态性可能与癌易感性相关,GG基因型可增加白种人群患癌风险,MCP-1基因A2518G位点有望作为癌早期诊断和预后判定的重要分子标志物。     

EB病毒感染及XRCC1、IL-10基因多态性与甲状腺癌的关联性分析

摘要 目的：探究Epstein-Barr病毒（EB病毒）感染及X射线交错互补修复因子1（XRCC1）、白介素-10（IL-10）基因多态性与甲状腺癌的关联性。方法：选取2020年1月~2022年12月132例甲状腺癌患者为研究组以及同期132例甲状腺良性腺瘤患者为对照组,采用原位杂交技术检测肿瘤标本EB病毒感染情况,聚合酶链反应-限制性内切酶片段长度多态性法检测XRCC1-399G/A位点、IL-10-592C/A位点基因多态性。结果：研究组EB病毒感染阳性率55.3%,高于对照组的33.3%（P<0.05）。研究组XRCC1-399G/A位点GA、AA基因型及A等位基因频率均高于对照组（P<0.05）;两组IL-10-592C/A各基因型频率比较差异无统计学意义,但研究组A等位基因频率高于对照组（P<0.05）。EB病毒感染阳性者较阴性者甲状腺癌风险增加3.337倍（95%CI：1.272~8.752）,携带XRCC1-399位点（GA+AA）型者较GG型风险增加2.438倍（95%CI：1.223~4.859）,携带IL-10-592位点（CA+AA）型者较CC型未增加甲状腺癌风险。不同病理类型甲状腺癌患者EB病毒感染情况及XRCC1-399位点、IL-10-592位点基因型分布比较差异均无统计学意义。结论：EB病毒感染阳性、XRCC1-399G/A位点突变基因型可能是甲状腺癌发病的易感因素,但二者与甲状腺癌病理类型无明显关系,而IL-10-592C/A基因多态性可能与甲状腺癌无关。     

环氧化物水解酶1基因(EPHXl)多态性与新生儿出生体重间关系分析

为研究母亲环氧化物水解酶1基因(EPHXl)多态性与新生儿出生体重间关系.收集了某纺织厂342名女工的资料,用PCR-限制性片段长度多态性法分析母亲EPHXl基因型,采用多元线性逐步回归模型分析母亲EPHXl多态性与新生儿出生体重关系.结果发现调整主要混杂因素后EPHXl的His139Arg/AG139Arg基因型与新生儿出生体重有显著性相关(β±SE＝-149g±56,P＝0.0083).经被动吸烟分层分析,结果显示仅在有被动吸烟史人群中EPHXl的Hus139Arg/Arg139Arg基因型与新生儿出生体重有显著性相关,(β±SE=-234g±88,P＝0.0088);而根据工作紧张程度分层分析后发现,仅在有工作紧张史人群中发现EPHXI的His139Arg/Arg139Arg基因型与新生儿出生体重有显著性相关(β±SE＝-157g±59,P＝0.0079).我们的结果显示母亲EPHXl多态性与新生儿出生体重有显著性相关,并存在基因-环境的交互作用.     

浙江地区汉族人群Toll样受体2基因Arg753Gln多态性和肺结核病相关性

应用聚合酶链反应-序列特异性引物方法(polymerase chain reaction with sequence specific primer,PCR-SSP),研究浙江地区汉族人群中Toll样受体2(Toll-like receptor2,TLR2)Arg753Gln(G2408A)单核苷酸多态性(single nucleotide polymorphism,SNP)分布及其与肺结核病的易感性的关系。分析了170名肺结核病患者和199名正常献血者TLR2基因Arg753Gln位点的基因型分布频率。结果表明,在170名肺结核病患者和199名正常献血者中,TLR2 Arg753Gln位点G/G基因型频率分别为58.23%和84.2%,G/A基因型频率分别为41.77%和15.8%,两种基因型在两组中相比较,差异显著,P<0.001。两组人群中均未发现有A/A基因型存在。TLR2基因Arg753Gln位点在浙江地区汉族人群中有其独特的分布规律,这个位点的多态性分布对肺结核病的发展有潜在的危险影响。     

山东地区肾上腺素能β3 受体基因多态性与冠心病的相关性研究

目的:研究山东地区肾上腺素能β3受体(β3-AR)基因多态性与冠心病及其危险因素的之间的关系。方法:对相互间无一级亲属关系的120例冠心病患者及114例非冠心病正常对照组人群,进行体重指数、腰臀围比、空腹血糖、血脂、血压、心电图、心脏彩超等检测,同时应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)核苷酸分型技术检测肾上腺素能β3受体基因及其基因多态性进行分析。结果:(1)冠心病组和正常对照组Trp64Trp、Trp64Arg和Arg64Arg的基因型频率分别为68.3%,30.0%,1.6%和69.2%,29.8%,0.9%。冠状动脉粥样硬化性心脏病组Arg等位基因频率(16.6%)与对照组(15.8%)频率近似(P>0.05),突变频率在冠心病与非冠心病之间相比无显著性差异。(2)多态性分布在冠状动脉粥样硬化性心脏病组不同冠脉病变支数亚组中也无显著性差异(x2=0.471,P=0.790)。结论:肾上腺素能β3受体基因Trp64Arg突变与山东地区人群冠心病的发生、发展无明显相关性。     

FcγR基因多态性与牙周炎易感性的Meta分析

目的探讨FcγRⅡa、FcγⅢa和FcγRⅢb的基因多态性与牙周炎发病风险性的相关性。方法通过检索PubMed、Web of Science、中国知网和万方等中英文数据库,纳入2019年10月前所有符合纳入标准的有关FcγRⅡa、FcγⅢa和FcγRⅢb的基因多态性与牙周炎发病风险性的研究,共27项病例对照研究,其中包含2 105个病例和1 115个对照,采用RevMan 5.3软件进行Meta分析,利用优势比(OR)及95%置信区间(CI)评价效应强度。结果 Meta分析结果合并显示FcγRⅡa和FcγRⅢb的基因多态性与牙周炎的发病风险无显著相关性,但FcγⅢa的基因多态性可能增加慢性牙周炎发病风险(V vs. F,OR=1.93,95%CI 1.01～3.69)。根据种群进行亚组分析,FcγRⅡa H131R位点的突变型可能会增加亚洲人群慢性或侵袭性牙周炎的发病风险[慢性牙周炎:R vs. H,OR=1.22,95%CI 1.04～1.42,(HR+RR)vs. HH,OR=1.28,95%CI 1.03～1.59;侵袭性牙周炎:R vs. H,OR=1.60,95%CI 1.01～2.54],但可能会降低高加索人群慢性牙周炎的发病风险[(HR+RR)vs. HH,OR=0.66,95%CI 0.48～0.90]。FcγⅢa F158V位点的突变型可能增加高加索人群慢性牙周炎的发病风险[V vs. F,OR=1.73,95%CI 1.06～2.85,(VV+FV)vs. FF,OR=2.26,95%CI 1.06～4.82]。FcγRⅢb NA1/NA2位点的NA2等位基因可能会降低包含50%高加索人群的混合人群侵袭性牙周炎的发病风险[(NA1NA2+NA2NA2)vs. NA1NA1,OR=0.57,95%CI 0.34～0.94)]。结论 FcγRⅡa、FcγⅢa和FcγRⅢb的基因多态性与牙周炎发病风险性之间的联系可能存在着种族差异,需要更大样本、更高质量的研究来进一步证实。     

IL-22基因多态性与中国人群肺结核易感性的相关性研究

本研究旨在探讨白细胞介素22(interleukin 22,IL-22)基因多态性位点与肺结核易感性的关系。采用SNPscan™多重单核苷酸多态性(single nucleotide polymorphism,SNP)分型技术,对453例肺结核患者(结核病组)和373例与患者长期密切接触者〔包括109例潜伏结核感染(latent tuberculosis infection,LTBI)者、264例健康对照者〕的IL-22基因的4个SNP位点(rs1179249、rs2227491、rs17224704、rs2227478)多态性进行分析。结核病组、LTBI组和对照组中4个SNP位点的基因型分布经哈温平衡(Hardy-Weinberg equilibrium,HWE)检验均处于遗传平衡状态。结果显示,rs17224704位点存在AA、TA和TT基因型。＞55岁人群中,此位点TA基因型在对照组中的分布显著高于结核病组(P＝0.047 9,OR＝0.365,95% CI＝0.135～0.991);AA基因型在LTBI组中的分布显著低于结核病组(P＝0.027 6);TA基因型在LTBI组中的分布显著高于结核病组(P＝0.007 37,OR＝0.213,95% CI＝0.069～0.660)。对照组和LTBI组的等位基因T频率显著高于结核病组(P＝0.026 9,OR＝0.388,95% CI＝0.167～0.897;P＝0.025 0,OR＝0.322,95% CI＝0.119～0.867)。IL-22基因rs17224704的多态性可能与中国重庆地区汉族人群肺结核易感性显著相关,其等位基因T可能是肺结核的保护基因。     

乳腺癌SULT1A1、ICAM5基因单核苷酸多态性的研究

目的:探讨硫酸基转移酶(sulfotransferase,SULT)lA1、细胞间粘附分子(ICAM5)基因多态性与女性乳腺癌易感性的关系.方法:采外周血DNA后用等位基因特异性扩增法(allele specific amplification,ASA)检测青岛市200例正常对照者和160例乳腺癌患者的SULTIA1、ICAM5基因多态性分布,并进行统计学分析.结果:(1)SULTlA1 Arg/Arg、Arg/His、His/His三种基因型分布在对照组和病例组之间的差异无显著意义(P=0.103);病例组、对照组His等位基因频率分别为19.5%和9.2%(P=0.039),此差别有统计学意义;在淋巴结转移方面SULTIA1基因三种基因型在阴、阳性组间的差异有统计学意义(P=0.038).(2)ICAM5基因各基因型及等位基因分布频率在病例组和对照组间的差异无显著意义(P=0.245,P=0.294);从临床病例分型方面进一步分析,基因型GG与携带变异基因A的GA及AA基因型相比差异均无统计意义.结论:SULTlA1 His等位基因与汉族女性乳腺癌的发生可能相关.     

CYP1A1基因单核苷酸多态性与肺癌的相关性研究

目的:探讨代谢酶CYP1A1基因MspI位点多态性与新疆汉族人群肺癌遗传易感性之间的相关性.方法:应用聚合酶链式反应(PCR)-限制性片段长度多态性(RFLP)技术检测59例新疆汉族肺癌和84例新疆汉族健康人的CYP1A1基因MspI位点多态性分布频率,并分析了CYP1A1基因MspI位点多态性与新疆汉族人群肺癌遗传易感性和患者性别之间的相关性.结果:(1)CYP1A1基因MspI位点3种多态基因型分布频率在两组间比较差异有统计学意义(χ2=6.682,P=0.035),CC基因型在病例组的分布频率显著高于正常对照组.(2)携带突变CC基因型的个体较携带TT基因型的个体患肺癌的危险性增加(OR=3.759.95%CI=1.228-11.494,P=0.035).(3)男女肺癌患者的CYP1A1基因MspI位点基因型及等位基因频率的差异均无显著性(P>0.05).结论:(1)CC突变基因型可能是新疆汉族人群的肺癌易感因素.(2)CYP1A1基因MspI位点多态性可能与新疆汉族肺癌患者的性别无关.     

No association between XRCC1 genetic polymorphisms and differentiated thyroid carcinoma risk: a meta-analysis

The X-ray repair cross-complementing group 1 (XRCC1) gene belongs to the family of DNA repair genes. Polymorphisms in the XRCC1 gene, Arg399Gln, Arg194Trp and Arg280His, have been reported to have implications in differentiated thyroid carcinoma (DTC) susceptibility, but the results remain conflicting and no meta-analysis has been published. Therefore, we carried out a systematic review of the published epidemiology studies, aiming to assess the relationship between XRCC1 polymorphisms and susceptibility to DTC risk. We selected three databases, PubMed, EMBASE and CNKI, in which to search for published literature. With respect to DTC risk associated with XRCC1, combined odds ratios (ORs) and 95 % confidence intervals (CI) were appropriately calculated on the basis of co-dominant, dominant and recessive models. To investigate different effects from specific race, subgroup analyses were carried out in Asian and Caucasian populations. Eight studies meeting the inclusion criteria were eventually selected for Arg399Gln (1,550 cases and 2,692 controls), five studies for Arg194Trp (858 cases and 1,394 controls) and five studies for Arg280His (1,237 cases and 2,267 controls). The combined results of the relevant studies exhibited that no significant associations with DTC risk were demonstrated for polymorphisms in XRCC1 Arg399Gln, Arg194Trp and Arg280His in all genetic models. Stratified analyses in Asian and Caucasian populations showed similar results. This meta-analysis arrives at a conclusion that the XRCC1 (Arg399Gln, Arg194Trp, Arg280His) polymorphisms appear to confer no risk for DTC.     

X-Ray Repair Cross-Complementing Group 1 (XRCC1) Genetic Polymorphisms and Cervical Cancer Risk: A HuGE Systematic Review and Meta-Analysis

Background

Previous studies investigating the association between X-ray repair cross-complementation group 1(XRCC1) polymorphisms and cervical cancer (CC) risk has provided inconsistent results. The aim of our study was to assess the association between the XRCC1 gene Arg399Gln, Arg194Trp, Arg280His polymorphisms and risk of CC.

Methods

Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before March 2011.Summary odds ratios (ORs) and 95% confidence intervals (CIs) for XRCC1 polymorphisms and CC were calculated in a fixed-effects model or a random-effects model when appropriate.

Results

Ultimately, 9, 5 and 2 studies were found to be eligible for meta-analyses of Arg399Gln, Arg194Trp and Arg280His, respectively. Our analysis suggested that the variant genotypes of Arg194Trp were associated with a significantly increased CC risk (Trp/Trp vs Arg/Arg, OR = 2.21, 95% CI = 1.60–3.06; Arg/Trp vs Arg/Arg, OR = 1.23, 95% CI = 1.02–1.49; dominant model, OR = 1.36, 95% CI = 1.14–1.63; recessive model, OR = 2.06, 95% CI = 1.51–2.82). For Arg280His polymorphism, no obvious associations were found for all genetic models. For Arg399Gln polymorphism, also no obvious associations were found for all genetic models. In the subgroup analyses by ethnicity/country, a significantly increased risk was observed among Asian, especially among Chinese. To get more precise evidences, adjusted ORs (95%CI) by potential confounders (such as age, ethnicity or smoking, etc) were also calculated for XRCC1 Arg399Gln and Arg194Trp, however, the estimated pooled adjusted OR still did not change at all.

Conclusion

This meta-analysis suggests that Arg194Trp polymorphism may be associated with CC risk, Arg399Gln polymorphism might be a low-penetrent risk factor for CC only in Asians, and there may be no association between Arg280His polymorphism and CC risk.     

XRCC1 Gene Polymorphisms and Glioma Risk in Chinese Population: A Meta-Analysis

Background

Three extensively investigated polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) in the X-ray repair cross-complementing group 1 (XRCC1) gene have been implicated in risk for glioma. However, the results from different studies remain inconsistent. To clarify these conflicts, we performed a quantitative synthesis of the evidence to elucidate these associations in the Chinese population.

Methods

Data were extracted from PubMed and EMBASE, with the last search up to August 21, 2014. Meta-analysis was performed by critically reviewing 8 studies for Arg399Gln (3062 cases and 3362 controls), 8 studies for Arg194Trp (3419 cases and 3680 controls), and 5 studies for Arg280His (2234 cases and 2380 controls). All of the statistical analyses were performed using the software program, STATA (version 11.0).

Results

Our analysis suggested that both Arg399Gln and Arg194Trp polymorphisms were significantly associated with increased risk of glioma (for Arg399Gln polymorphism: Gln/Gln vs. Arg/Arg, OR = 1.82, 95% CI = 1.46–2.27, P = 0.000; Arg/Gln vs. Arg/Arg, OR = 1.25, 95% CI = 1.10–1.42, P = 0.001 and for Arg194Trp polymorphism: recessive model, OR = 1.78, 95% CI = 1.44–2.19, P = 0.000), whereas the Arg280His polymorphism had no influence on the susceptibility to glioma in a Chinese population.

Conclusions

This meta-analysis suggests that there may be no association between the Arg280His polymorphism and glioma risk, whereas the Arg399Gln/Arg194Trp polymorphisms may contribute to genetic susceptibility to glioma in the Chinese population. Nevertheless, large-scale, well-designed and population-based studies are needed to further evaluate gene-gene and gene–environment interactions, as well as to measure the combined effects of these XRCC1 variants on glioma risk.     

Association of X-Ray Repair Cross-Complementing Group 1 Arg194Trp,Arg399Gln and Arg280His Polymorphisms with Head and Neck Cancer Susceptibility: A Meta-Analysis

Background

Previous studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk.

Methods

The PubMed and EMBASE databases were searched for genetic association studies on the XRCC1 Arg194Trp, Arg399Gln, and Arg280His polymorphisms and HNC risk. (The most recent search was conducted on 20 August, 2013.) Twenty-six studies were identified and meta-analysis was performed to evaluate the association between the polymorphism and HNC by calculating combined odds ratios and 95% confidence intervals.

Results

No significant association was found under the allelic, homozygous, heterozygote, and dominant genetic models in the overall comparison. Further, no significant association between the XRCC1 Arg399Gln and Arg280His polymorphisms and HNC risk was detected under the four genetic models in subgroup analyses based on ethnicity, cancer site, and whether or not the studies had been adjusted for cigarette smoking and alcohol. However, in stratified analyses based on cancer site, a significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer under the allelic, heterozygote, and dominant models. The XRCC1 Arg194Trp polymorphism was significantly associated with HNC risk in studies that were adjusted for smoking and alcohol under the homozygous and heterozygote models.

Conclusion

The meta-analysis results suggest that the XRCC1 Arg399Gln and Arg280His polymorphisms are probably not associated with the risk of HNC, but the XRCC1 Arg194Trp polymorphism was associated with increased risk of HNC in the subgroup analysis of studies adjusted for smoking and alcohol and with increased risk of oral cancer in the stratified analyses based on cancer site. Further studies with larger samples are needed to confirm these findings.     

Genetic Polymorphisms of XRCC1 and Leukemia Risk: A Meta-Analysis of 19 Case-Control Studies

Objective

Three common X-ray repair cross-complementing groups 1 (XRCC1) polymorphisms, Arg399Gln, Arg194Trp, and Arg280His, have been reported to be implicated in the development of leukemia. However, previous results from different studies were inconsistent. Consequently, we performed a meta-analysis in order to accurately evaluate the association between XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms and leukemia risk.

Methods

Through computerized searching of PubMed, ISI Web of Knowledge, Cochrane, EBSCO, and OpenGrey databases, and manually searching relevant references, a total of 19 studies with 3387 cases and 6168 controls for Arg399Gln (G>A) polymorphism, 12 studies with 2043 cases and 4550 controls for Arg194Trp (C>T), and 6 studies with 1445 cases and 1905 controls for Arg280His (G>A) were collected to perform meta-analysis and stratified analysis to explore the associations between these variants and leukemia susceptibility. Based on three genetic models, the codominant model, dominant model and recessive model, odds ratios (ORs) as well as their 95% confidence intervals (CIs) were used to evaluate the association strength between XRCC1 genotypes and leukemia risk.

Results

With respect to overall leukemia susceptibility, no association was detected. In stratified analyses by tumor type, Arg399Gln was associated with higher acute lymphoblastic leukemia (ALL) risk (AA vs. GG, OR  =  1.50, 95% CI: 1.11-2.02; AA+GA vs. GG, OR  =  1.35, 95% CI: 1.02-1.78). Additionally, Arg399Gln, Arg194Trp, and Arg280His may influence the susceptibilities of some leukemia type and race populations.

Conclusion

This meta-analysis indicates these three polymorphisms of XRCC1 do not associate with overall leukemia risks but could be associated with the risks for some specific subgroups.     

Associated risk of XRCC1 and XPD cross talk and life style factors in progression of head and neck cancer in north Indian population

Effective DNA repair machinery ensures maintenance of genomic integrity. Environmental insults, ageing and replication errors necessitate the need for proper DNA repair systems. Any alteration in DNA repair efficacy would play a dominant role in progression of squamous cell carcinoma of head and neck (SCCHN). Genotypes of XRCC1 gene-Arg194Trp, Arg280His, Arg399Gln and XPD Lys751Gln, by PCR-RFLP were studied in 278 SCCHN patients and an equal number of matched healthy controls residing in north India. In XRCC1 polymorphisms, Arg194Trp and Arg399Gln variants showed a reduced risk, whereas, XPD Lys751Gln variants exhibited ～2-fold increase in SCCHN risk. With XRCC1-Arg280His variants, there was no association with SCCHN risk. Arg399Gln of XRCC1 appears to have a protective role in people those consume alcohol, while XPD Lys751Gln variants indicated ～2-fold increased risk of SCCHN in all the co-variate groups. Comparison of gene-gene interaction among XRCC1 Arg280His and XPD Lys751Gln suggested enhanced risk of SCCHN by ～2.3-fold in group one and ～6.1-fold in group two. In dichotomized groups of this combination, the risk was ～2.4 times. Haplotype analysis revealed the frequency of C-G-G-G and C-A-G-G to be significantly associated with an increased risk of SCCHN. On the contrary, T-G-A-A significantly diminished the risk. CART analysis results showed that the terminal node that contains homozygous mutants of XPD Lys751Gln and XRCC1 Arg194Trp, wild type of XRCC1 Arg399Gln and homozygous mutant of XRCC1 Arg280His, represent the highest risk group. Our results demonstrate high degree of gene-gene interaction involving DNA repair genes of NER and BER pathways, namely XRCC1 and XPD. This study amply demonstrates positive association of XPD Arg751Gln polymorphism with an increased risk of SCCHN. Further, XRCC1 Arg280His variant though dormant individually, may also contribute to the development of cancer in combination with XPD Arg751Gln.     

Polymorphisms of XRCC1 and gastric cancer susceptibility: a meta-analysis

Studies investigating the association between X-ray repair cross-complementing gene 1 (XRCC1) polymorphisms and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case–control and cohort studies to better compare results between studies. Published literature from PubMed, EMBASE, and China National Knowledge Infrastructure were retrieved. 18 studies with 3,915 GC cases and 6,759 controls were selected. For XRCC1 Arg194Trp polymorphism, we only found the Trp/Trp genotype carriers might be at high risk of GC (TT vs. CC+CT: OR = 1.31, 95%CI = 1.04–1.65). When stratifying for ethnicity, the results showed there was a significant difference in genotype distribution between GC cases and controls among Asians (especially, in Chinese population), but not among Caucasians. When stratifying for control sources, significant association between Arg194Trp polymorphism and GC risk was only observed in the hospital-based controls’ subgroup (TT vs. CC+CT: OR = 1.45, 95%CI = 1.13–1.87). Additionally, no significant association was detected in the gastric cardia cancer’s subgroup. The results of the overall meta-analysis did not suggest any association between Arg280His/Arg399Gln polymorphisms and GC susceptibility for all genetic models. There was no evidence for the association between these two gene polymorphisms and GC risk in subgroup analyses based on study design, ethnicity, country, tumor location, Helicobacter pylori infection and the Lauren’s classification of GC. In conclusion, XRCC1 Arg194Trp homozygous mutant genotype (Trp/Trp) was found to be associated with increased risk of GC.     

Deoxyribonucleic acid repair gene X-ray repair cross-complementing group 1 polymorphisms and non-carcinogenic disease risk in different populations: A meta-analysis

PURPOSE:

This study aims to assess a meta-analysis of the association of X-ray repair cross-complementing group 1 (XRCC1) polymorphisms with the risk of various non-carcinogenic diseases in different population.

MATERIALS AND METHODS:

This meta-analysis was performed by critically reviewing reveals 38 studies involving 10043 cases and 11037 controls. Among all the eligible studies, 14 focused on Arg194Trp polymorphism, 33 described the Arg399Gln and three articles investigated on Arg280His. Populations were divided into three different ethnic subgroups include Caucasians, Asians and other (Turkish and Iranian).

RESULTS:

Pooled results showed no correlation between Arg194Trp and non-carcinogenic disease. There was only weak relation in the recessive (odds ratio [OR] =1.11, 95% confidence interval [CI]: 0.86-1.44) model in Asian population and dominant (OR = 1.04, 95% CI: 0.66-1.63) model of other populations. In Arg399Gln polymorphism, there was no relation with diseases of interest generally. In the pooled analysis, there were weak relation in the dominant (OR = 1.08, 95% CI: 0.86-1.35) model of Asian population and quite well-correlation with recessive (OR = 1.49, 95% CI: 1.19-1.88), dominant (OR = 1.23, 95% CI: 0.94-1.62), and additive (OR = 1.23, 95% CI: 0.94-1.62) models of other subgroup. For Arg280His, there was a weak relation only in the dominant model (OR = 1.06, 95% CI: 0.74-1.51).

CONCLUSION:

The present meta-analysis correspondingly shows that Arg399Gln variant to be associated with increased non-carcinogenic diseases risk through dominant and recessive modes among Iranian and Turkish population. It also suggests a trend of dominant and recessive effect of Arg280His variant in all population and its possible protective effect on non-carcinogenic diseases.     

Association between XRCC1 and XRCC3 polymorphisms and colorectal cancer risk: a meta-analysis of 23 case–control studies

Several potential functional polymorphisms in the DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln (rs25487), Arg194Trp (rs1799782), Arg280His (rs25489) and X-ray repair cross-complementing group 3 (XRCC3) T241M (rs861539) have been implicated in colorectal cancer (CRC) risk, but the results are conflicting. Here, we performed a meta-analysis of 23 published case control datasets and assessed genetic heterogeneity between those datasets. All the case–control studies published from January 2000 to June 2012 on the association between those polymorphisms and CRC risk were identified by searching the electronic literature Medline. Statistical analysis was performed with the software programs Review Manager (version 4.2). For overall CRC, no significant association was observed, the pooled odds ratios for XRCC1 Arg399Gln, Arg194Trp, Arg280His, and XRCC3 T241M were 1.02 (95 % CI: 0.93, 1.12), 1.03 (95 % CI: 0.94, 1.14), 0.98 (95 % CI: 0.85, 1.13) and 1.03 (95 % CI: 0.85, 1.26), respectively. Furthermore, no significant association was observed in subgroup analyses based on ethnicity. The results suggested that these four SNPs evaluated are not associated with risk of CRC.