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

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

IGF-1和IGFBP-3基因多态性与非吸烟女性肺癌关联研究

  目的   探讨胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）单核苷酸多态性与非吸烟女性肺癌发病的关系。   方法   采用TaqMan单核苷酸多态性分型技术,检测287例中国汉族女性肺癌患者和281例正常女性对照者IGF-1和IGFBP-3基因位点的基因型。   结果   IGF-1基因rs2946834位点的三种基因型（CC/CT/TT）在女性非吸烟肺癌患者和对照间的分布具有显著性差异（P < 0.001）,与TT基因型相比,CC基因型显著降低女性肺癌的发病风险（OR=0.28,95%CI:0.15~ 0.54）。另外,在非吸烟女性中,IGF-1（rs1520220）GG基因型可降低晚期肺癌发病风险（OR=0.30,95%CI:0.09~0.96）。   结论   IGF-1基因单核苷酸多态性可能与女性非吸烟肺癌的发病相关,这一结论有待于大样本以及功能学研究的进一步证实。      

pre-miR-27a单核苷酸多态与非吸烟女性肺癌发生的相关性

目的:探讨miR-27a(rs895819,A>G)多态与非吸烟女性肺癌发生的相关性。方法:采用病例-对照研究方法,使用PCR-RFLP技术检测90例非吸烟女性原发性肺癌患者和97例非吸烟女性体检者rs895819位点基因型分布频率。非条件Logistic统计分析不同基因型与肺癌发生的相关性,并分析该多态与烹饪油烟暴露的协同效应及与临床参数的相关性。结果:肺癌组rs895819 位点GG突变基因型和G等位基因频率明显高于对照组(P=0.047,P=0.016)。AG+GG基因型明显增加了非吸烟女性肺癌的发生风险(OR=1.82,95%CI=1.01～3.28,P=0.038)。肺癌组和对照组烹饪油烟暴露率分别为57%和42%,差异有统计学意义(P=0.035)。回归分析显示该多态位点与烹饪油烟无交互作用;与临床病理特征(病理类型,临床分期和淋巴结转移)均无相关性。结论:has-miR-27a rs895819 G等位基因增加了非吸烟女性肺癌发生的风险。     

Mena表达及SNPs与胃癌遗传易感性及预后

  目的  探讨Mena表达与胃癌侵袭转移的相关性及SNPs与胃癌遗传易感性的关系。  方法  制作模拟胃癌侵袭转移过程的组织芯片,免疫组化染色检测Mena蛋白的表达。PCR-LDR技术检测Mena基因5个SNPs位点多态性并行测序验证。  结果  胃腺癌中Mena表达上调,肠型与混合型胃癌高于弥漫型,并与胃癌侵袭转移负相关,Mena高表达者预后好。Mena基因SNP位点rs3795443的188例对照组等位基因A、G的频率分别为91.0% 和9.0%,胃癌病例组等位基因A、G的频率为82.4% 和17.6%;AA、A/G和GG的基因型频率在对照组分别为81.9%、18.1%和0,而在病例组为68.35%、28.09% 和3.56%,差异具有统计学意义（OR=2.1489,95%CI:1.4607~3.1613,P < 0.01）。5个SNPs位点的基因型和等位基因频率与胃癌术后生存时间均无明显相关性。  结论  胃癌Mena表达升高,组织学类型的维持以及侵袭转移与其表达密切相关,高表达者预后好。Mena SNP rs3795443位点携带等位基因G的GG和A/G基因型个体的胃癌患病风险提高,提示检测该位点基因型有助于评估胃癌的遗传易感性。      

硫酸基转移酶1E1基因单核苷酸多态性联合吸烟与肺癌易感性的关系

目的:研究硫酸基转移酶(sulfotransferase,SULT)1E1基因的单核苷酸多态性(single nucleotide polymorphism,SNP)联合吸烟与肺癌易感性的关系.方法:采用病例-对照研究,收集原发性肺癌患者351例和非肿瘤患者207例,应用AllGloTM探针结合实时荧光PCR方法分析肺癌组和对照组中SLUT1E1多态位点A-3037G(rs4149525)基因型分布情况,比较不同基因型联合吸烟与肺癌易感性的关系,以及对肺癌不同病理类型的影响. 结果:肺癌患者A-3037G多态位点的AA、AG、GG基因型和A、G等位基因频率分布与对照组比较,差异无统计学意义(P>0.05).吸烟≥30包年的野生型纯合子个体罹患肺癌的风险增加,调整比值比(odds ratio,OR)为2.307[95%可信区间(confidence interval,CI)为1.285～3.976,P<0.05];吸烟≥30包年携带突变等位基因G的个体患肺癌的风险可能增加,调整OR值为1.523(95%CI为0.987～2.961,P=0.05).3种基因型联合吸烟(≥30包年)可能增加了罹患肺鳞癌的风险,AA和AG+GG基因型的OR值分别为5.983(95%CI为2.786～12.850,P<0.01)和2.750(95%CI为1.245～6.075,P<0.05);而突变等位基因G对不吸烟个体似乎具有保护作用,OR值为0.296(95%CI为0.101～0.864,P<0.05);A-3037G多态性联合吸烟对肺腺癌的发病风险没有显著影响.结论:SULT1E1基因启动子区A-3037G多态性联合吸烟可能对肺癌的发病风险有一定影响.     

髓过氧化物酶基因-463G/A多态与中国人肺癌遗传易感性

目的 研究髓过氧化物酶（MPO）基因－463G→A单核苷酸多态与肺癌易感性的关系。方法 以PCR－单链构像多态（SSCP）技术,分析了314例肺癌患者和320例正常对照者MPO基因启动子区第－463位核苷酸多态基因型分布,及其与肺癌风险的关系。结果 正常对照组中G和A等位基因频率分别为85.0%和15.0%,而肺癌患者分别为89.0%和11.0%。携带MPO－463GG基因型的个体患肺癌风险比携带GA和AA基因型个体高1.7倍（校正的OR为1.7;95%CI为1.2-2.5）,且此种风险增高只限于肺鳞癌（OR为2.4;95%CI为1.4-3.9）,而与肺腺癌无关（OR为1.3;95%CI为0.8-2.1）。分层分析结果表明,与GA和AA基因型比较,GG基因型并不增加非吸烟者和累积吸烟量＜26包年者患肺癌的风险,但在累积吸烟量≥26包年的吸烟者中,GG基因型发生肺鳞癌的风险比GA和AA基因型高3.3倍。结论 MPO－463 A等位基因显著降低中国人发生吸烟相关性肺鳞癌的风险。     

SMAD4基因单核苷酸多态性位点rs12958604和rs10502913与宫颈癌相关性研究

  目的  探讨SMAD4基因单核苷酸多态性（single nucleotide polymorphism,SNP）位点rs12958604和rs10502913与宫颈癌遗传易感性之间的关系。  方法  收集2018年2月至2019年12月右江民族医学院附属医院和广西医科大学附属肿瘤医院确诊的宫颈癌患者和健康体检者血液样本各342例及其临床病理资料,分为宫颈癌组和对照组,采用DNA测序法和SNaPshot技术检测SNP ,分析比较两组rs12958604和rs10502913基因型、等位基因、基因模型、单倍型差异性。  结果  两组SMAD4的rs10502913基因型及等位基因进行比较差异均无统计学意义（均P>0.05）,两组SMAD4的rs12958604 GG基因型和GG+GA显性模型及G等位基因进行比较差异均具有统计学意义（OR=0.577,95%Cl:0.380～0.877,P=0.010; OR=0.670,95%Cl:0.483～0.928,P=0.016 及OR=0.743,95%Cl:0.600～0.920,P=0.006）。单倍型分析显示G-A和G-G在两组中差异均具有统计学意义（均P<0.05）。多元Logistic回归多因素分析显示高血压是独立危险因素。  结论  SMAD4基因SNP位点rs12958604与宫颈癌易感性可能存在关联。      

PLCε1基因多态性与食管癌遗传易感性的关联研究

  目的  探讨PLCε1基因rs2274223 A/G单核苷酸多态性(single nucleotide polymorphism,SNP)和rs11599672 T/G SNP与河北省磁县高发区人群食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)遗传易感性之间的关系。  方法  采用聚合酶链反应-连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)方法对527例ESCC患者和527例健康对照PLCε1基因rs2274223 A/G SNP和rs11599672 T/G SNP进行基因分型。  结果  ESCC患者组上消化道肿瘤(upper gastrointestinal cancer,UGIC)家族史阳性个体比例为48.6%,显著高于健康对照组(39.3%,χ2=9.25,P=0.002)。ESCC患者组及健康对照组PLCε1基因rs2274223 A/G SNP AA、AG、GG基因型频率分别为48.0%、43.9%、8.1%和57.1%、37.5%、5.4%。与AA基因型相比,携带AG、GG、AG/GG基因型可能增加ESCC的发病风险,经年龄、性别、吸烟状况、UGIC家族史校正后的OR值分别为1.41(95%CI=1.09~ 1.83)、1.71(95%CI=1.03~2.86)、1.45(95%CI=1.13~1.85)。PLCε1基因rs11599672 T/G SNP等位基因频率和基因型频率总体分布在ESCC患者组及健康对照组之间无显著性差异(P>0.05)。应用2LD软件对PLCε1基因rs2274223 A/G SNP和rs11599672 T/G SNP进行联合分析显示,两个多态性位点间不存在连锁不平衡现象(D'=0.11)。与最常见的AT单体型相比,GT单体型增加了ESCC的发病风险(OR=1.36,95%CI=1.08~1.71)。  结论  PLCε1基因rs2274223 A/G SNP可以作为高发区人群ESCC遗传易感性的标志物。UGIC家族史阳性个体、携带PLCε1基因rs2274223 A/G SNP AG、GG基因型的个体罹患ESCC的风险较高,应定期接受食管内镜检查,以便真正实现ESCC的早期诊断、早期治疗。      

DNA修复基因XPD G312A多态性与肺癌易感性关系的meta分析

背景与目的已有的研究结果显示DNA修复基因XPD G312A多态位点与肺癌发生存在相关性,但研究结果尚未有一致性结论。本研究旨在通过meta分析的方法,综合评价DNA修复基因XPD G312A多态位点与肺癌发病风险的相关性。方法检索PUBMED、EMBASE、清华CNKI全文数据库、万方全文数据库中XPD基因G312A多态位点与肺癌易感性关系的病例对照研究。对符合纳入标准的研究用meta分析的方法进行数据合并,采用RevMan5.0和STATA11.0评价研究间异质性,计算合并OR值及95%CI。并进行敏感性分析和发表偏倚检验。结果共纳入18项研究,累计病例6554例,对照8322例。总体人群中A等位基因及AA基因型携带者肺癌风险明显升高(A vs G:OR=1.06,95%CI:1.00-1.12;AA vs AG+GG:OR=1.20,95%CI:1.06-1.36;AA vs GG:OR=1.19,95%CI:1.04-1.36)。亚洲人群中,AA基因型携带者肺癌风险明显升高(AA vs AG+GG:OR=7.15,95%CI:1.90-26.94;AA vs GG:OR=7.20,95%CI:1.91-27.15)。高加索人群中,AA基因型携带者肺癌风险升高(AA vs AG+GG:OR=1.15,95%CI:1.01-1.31)。结论XPD312A等位基因为肺癌发生的风险等位基因,AA基因型携带者肺癌风险升高,尤其在亚洲人群这种影响更为明显。     

云南省汉族人群TNF-α基因多态性与非小细胞肺癌发生、发展的相关性

背景与目的：肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）不仅是一种重要的炎症因子,还与肿瘤的发生、发展密切相关。探讨TNF-α基因多态性与云南省汉族人群非小细胞肺癌（non-small cell lung cancer,NSCLC）发生、发展的相关性。方法：选取云南省425例汉族人群NSCLC病例和438名健康体检者,采用TaqMan探针基因分型法对TNF-α基因启动子区域5个单核苷酸多态性（single nucleotide polymorphism,SNP）位点rs1799964（-1031T>C）、rs1800630（-863C>A）、rs1799724（-857C>T）、rs1800629（-308G>A）和rs361525（-238G>A）进行基因分型并分析其等位基因、基因型及所构建的单倍型在NSCLC病例及健康对照者中的频率差异。结果：TNF-α基因启动子5个SNP位点的等位基因和基因型频率在NSCLC病例组和对照组间差异无统计学意义（P＞0.05）。病例分层分析发现,rs1799724（C>T）的T等位基因在腺癌组中的频率显著高于对照组（P=0.010,OR=1.56,95% CI：1.11~2.19）,在显性模式下携带T等位基因的个体（TT+CT）患肺腺癌的风险显著升高（P=0.007,OR=1.66,95% CI：1.15~2.42）。rs1800630（C>A）的A等位基因在腺鳞癌及其他类型肺癌组中的频率显著高于对照组,差异有统计学意义（P=0.013,OR=2.15,95% CI：1.16~3.96）。单倍型分析结果显示,单倍型rs1799724T-rs1800629G在腺癌组中的频率显著高于对照组（P=0.048,OR=1.42,95% CI：1.00~2.01）。结论：位于TNF-α基因启动子区域的SNP位点rs1799724（C>T）等位基因T和基因型TT可能是云南省汉族人群NSCLC中腺癌发生的风险性因素。SNP位点rs1800630（C>A）等位基因A可能是云南省汉族人群NSCLC中腺鳞癌及其他类型肺癌发生的风险性因素。     

TP63 Gene Polymorphisms,Cooking Oil Fume Exposure and Risk of Lung Adenocarcinoma in Chinese Non-smoking Females

Background: Genetic polymorphisms of TP63 have been suggested to influence susceptibility to lungadenocarcinoma development in East Asian populations. This study aimed to investigate the relationship betweencommon polymorphisms in the TP63 gene and the risk of lung adenocarcinoma, as well as interactions of thepolymorphisms with environmental risk factors in Chinese non-smoking females. Methods: A case-control studyof 260 cases and 318 controls was conducted. Data concerning demographic and risk factors were obtained foreach subject. The genetic polymorphisms were determined by Taqman real-time PCR and statistical analyseswere performed using SPSS software. Results: For 10937405, carriers of the CT genotype or at least one T allele(CT/TT) had lower risks of lung adenocarcinoma compared with the homozygous wild CC genotype in Chinesenonsmoking females (adjusted ORs were 0.68 and 0.69, 95%CIs were 0.48-0.97 and 0.50-0.97, P values were0.033 and 0.030, respectively). Allele comparison showed that the T allele of rs10937405 was associated with adecreased risk of lung adenocarcinoma with an OR of 0.78 (95%CI=0.60-1.01, P=0.059). Our results showed thatexposure to cooking oil fumes was associated with increased risk of lung adenocarcinoma in Chinese nonsmokingfemales (adjusted OR=1.58, 95%CI=1.11-2.25, P=0.011). However, we did not observe a significant interaction ofcooking oil fumes and TP63 polymorphisms. Conclusion: TP63 polymorphism might be a genetic susceptibilityfactor for lung adenocarcinoma in Chinese non-smoking females, but no significant interaction was found withcooking oil fume exposure.     

2q35 rs13387042和8q24 rs13281615单核苷酸多态性与中国东北汉族绝经前妇女乳腺癌风险关系

背景与目的：乳腺癌作为中国女性最常见的恶性肿瘤,每年的新发数量和死亡数量分别占全世界的12.2%和9.6%,但与中国乳腺癌患者明显相关的基因多态位点至今尚不清楚。本研究旨在探讨2q35 rs13387042和8q24 rs13281615单核苷酸多态性与中国北方汉族绝经前妇女乳腺癌风险关系,为预防和治疗乳腺癌提供循证依据。方法：采用多重单碱基延伸单核苷酸多态性分型技术(SNaPshot)分析方法,检测了280例绝经前乳腺癌患者和287例绝经前正常对照者2q35 rs13387042和8q24 rs13281615多态性位点基因型,并比较不同基因型和等位基因与乳腺癌风险的关系。结果：2q35 rs13387042多态性位点基因型频率在乳腺癌和对照样本之间差异有统计学意义(P=0.017);8q24 rs13281615多态性位点基因型频率在乳腺癌和对照样本之间差异无统计学意义(P=0.967)。Logistic回归分析结果显示,对于2q35 rs13387042位点,与GG相比,GA和GA+AA基因型携带者显著增加乳腺癌的患病风险(OR=1.793,95%CI：1.177～2.733,P=0.007;OR=1.691,95%CI：1.122～2.550,P=0.012),而AA携带者与乳腺癌的患病风险无关(OR=0.572,95%CI：0.104～3.153,P=0.521);与G等位基因相比,A等位基因显著增加乳腺癌的患病风险(OR=1.505,95%CI：1.033～2.193,P=0.033)。对于8q24rs13281615位点,与AA相比,AG、GG和AG+GG基因型携带者与乳腺癌的患病风险无关(OR=0.992,95%CI：0.660～1.490,P=0.968;OR=1.047,95%CI：0.642～1.708,P=0.853;OR=1.007,95%CI：0.682～1.487,P=0.971);与A等位基因相比,G等位基因不增加乳腺癌患病风险(OR=1.021,95%CI：0.809～1.288,P=0.863)。结论：本实验证实2q35 rs13387042多态性位点能够增加中国北方汉族绝经前妇女乳腺癌易感风险,而8q24 rs13281615多态性位点与中国北方汉族绝经前妇女乳腺癌易感性无明显相关性。     

Associations of ERCC4 rs1800067 Polymorphism with Cancer Risk: an Updated Meta-analysis

Background: Results from previous studies concerning the association of ERCC4 rs1800067 polymorphismwith risk of cancer were inconsistent. To explore the exact relation with susceptibility, we conducted the presentmeta-analysis. Materials and Methods: Literature of electronic databases including PubMed, Web of Science,EMBASE, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically searched. ORsand their 95%CIs were used to assess the strength of associations between ERCC4 polymorphism and cancerrisk. Results: There was no significant association between ERCC4 rs1800067 AA or AG genotypes and overallrisk of cancer (AA vs. GG: OR=0.998, 95%CI=0.670-1.486, P=0.992; AG vs. GG: OR=0.970, 95%CI=0.888-1.061, P=0.508). A dominant genetic model also did not demonstrate significant association of (AA+AG)genotype carriers with altered risk of overall cancer (OR=0.985, 95%CI=0.909-1.068, P=0.719). In addition,no significant association was observed between A allele of ERCC4 rs1800067 A/G polymorphism and alteredcancer risk compared with G allele (OR=0.952, 95%CI=0.851-1.063, P=0.381). Subgroup analysis suggestedthat AA genotype carriers were significantly associated with decreased risk of glioma compared with wild-typeGG genotype individuals (OR=0.523, 95%CI=0.275-0.993, P=0.048). For subgroup of lung cancer, A allele ofERCC4 rs1800067 A/G polymorphism was significantly associated with decreased risk of lung cancer comparedwith G allele (OR=0.806, 95%CI=0.697-0.931, P=0.003). Conclusions: This meta-analysis indicated that ERCC4rs1800067 A/G polymorphism might not be associated with risk of overall cancer. However, individuals with theAA genotype were associated with significantly reduced risk of glioma compared with wild-type GG genotype;The A allele was associated with significantly reduced risk of lung cancer compared with G allele. Future largescalestudies performed in multiple populations are warranted to confirm our results.     

The DNA Repair Gene ERCC6 rs1917799 Polymorphism is Associated with Gastric Cancer Risk in Chinese

Objective: Excision repair cross-complementing group 6 (ERCC6) is a major component of the nucleotideexcision repair pathway that plays an important role in maintaining genomic stability and integrity. Severalrecent studies suggested a link of ERCC6 polymorphisms with susceptibility to various cancers. However, therelation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive. In this sex- and age- matchedcase-control study including 402 GC cases and 804 cancer-free controls, we aimed to investigate the associationbetween a potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory region and GC risk.Methods: The genotypes of rs1917799 were determined by Sequenom MassARRAY platform and the status ofHelicobacter pylori infection was detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95%confidential interval (CI) were calculated by logistic regression analysis. Results: Compared with the commonTT genotype, the ERCC6 rs1917799 GG genotype was associated with increased GC risk (adjusted OR=1.46,95%CI: 1.03-2.08, P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrateda statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01-1.89, P=0.044). This was alsoobserved for the male subpopulation (GG vs. TT: adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs.T allele: adjusted OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended to beenhanced by H. pylori infection, smoking and drinking, but their interaction effects on GC risk did not reachstatistical significance. Conclusions: ERCC6 rs1917799 GG genotype might be associated with increased GCrisk in Chinese, especially in males.     

Role of DNA Repair-related Gene Polymorphisms in Susceptibility to Risk of Prostate Cancer

Aim: We assessed the association between genetic variants of XPG, XPA, XPD, CSB, XPC and CCNH inthe nucleotide excision repair (NER) pathway and risk of prostate cancer. Methods: We genotyped the XPG,XPA, XPD, CSB, XPC and CCNH polymorphisms by a 384-well plate format on the MassARRAY® platform.Multivariate logistical regression analysis was used to assess the associations between the six gene polymorphismsand risk of prostate cancer. Results: Individuals carrying the XPG rs229614 TT (OR=2.01, 95%CI=1.35-3.27)genotype and T allele (OR=1.73, 95%CI=1.37-2.57) were moderately significantly associated with a higher riskof prostate cancer. Subjects with XPD rs13181 G allele had a marginally increased risk of prostate cancer, withadjusted OR(95%CI) of 1.53 (1.04-2.37). Moreover, individuals carrying with CSB rs2228526 GG genotype(OR=2.05, 95% CI=1.23-3.52) and G allele (OR=1.56, 95%CI=1.17-2.05) were associated with a higher increasedrisk of prostate cancer. The combination genotype of XPG rs2296147 T and CSB rs2228526 G allele hadaccumulative effect on the risk of this cancer, with an OR (95% CI) of 2.23(1.37-3.59). Conclusions: Our studyindicates that XPG rs2296147 and CSB rs2228526 polymorphisms are significantly associated with increasedrisk of prostate cancer, and that combination of XPG rs2296147 T allele and CSB rs2228526 G allele is stronglyassociated with an increased risk.     

MDM2 and TP53 Polymorphisms as Predictive Markers for Head and Neck Cancer in Northeast Indian Population: Effect of Gene-Gene and Gene-Environment Interactions

Background: Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increasethe susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also stronglyassociated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In acase-control study, we investigated the significance of the above polymorphisms alone, and upon interaction withone another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population.Materials and Methods: Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthycontrols was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing.Results: Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to thosewith the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in femalesby ~4-fold (OR=4.6, 95% CI: 1.1-19.4) (P=0.04). TP53 polymorphism did not contribute to HNC risk alone;however, interaction between the TP53 GC and MDM2 GG genotypes resulted in significant risk (OR=4.9, 95%CI: 0.2-105.1) (p=0.04). Smokers, BQ- chewers and alcohol consumers showed statistically significant and dosedependentincrease in HNC risk, irrespective of the MDM2 genotype. Conclusions: MDM2 genotype could serveas an important predictive biomarker for HNC risk in the population of Northeast India.     

中国汉族人群DNA聚合酶ε基因POLE1单核苷酸多态性与肺癌易感性的关系

目的：探讨人类DNA聚合酶ε基因POLE1单核苷酸多态性（SNP）与肺癌易感性间的关系。方法：采用病例对照研究方法,选择经组织学确诊的肺癌患者462例,以及相同地区,性别年龄频数匹配的对照466例,针对经筛选的5个SNP进行基因型检测,通过统计分析研究基因频率与肺癌风险的关系,并探讨吸烟在其中的影响。结果：病例组rs5744738基因频率分布高于对照组（P〈0.05）。A/A纯合变异携带人群的患肺癌风险显著降低（校正OR=0.47,95%CI：0.25～0.91）。在分层分析中,60岁以上人群患肺癌的风险显著下降（校正OR=0.28,95%CI：0.09～0.91）,无患肿瘤家族史人群下降到0.42倍（校正OR=0.42,95%CI：0.19～0.90）。随着吸烟量的增加,G/G或G/A基因型人群肺癌风险显著升高。rs5744962变异位点（T→C）可提高非吸烟人群的患肺癌风险至1.75倍（95%CI：1.02～3.00）。结论：选取的5个人类POLE1基因SNP的多态性可能与中国汉族人群肺癌遗传易感性有关,在携带rs5744738及与之紧密连锁的rs4883545、rs5744873突变纯合基因的人群,患肺癌的风险显著降低,而携带rs5744962、rs5745047突变基因位点的非吸烟人群患肺癌的风险升高。     

Analysis of TP53 Polymorphisms in North Indian Sporadic Esophageal Cancer Patients

Background: To investigate the relationship of five TP53 polymorphisms (p.P47S, p.R72P, PIN3 ins16bp,p.R213R and r.13494g>a) with the esophageal cancer (EC) risk in North Indians. Materials and Methods:Genotyping of p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a polymorphisms of TP53 in 136 sporadicEC patients and 136 controls using polymerase chain reaction and PCR-RFLP. Results: The frequencies ofgenotype RR, RP and PP of p.R72P polymorphism were 16.91 vs 26.47%, 58.82 vs 49.27% and 24.27 vs 24.27%among patients and controls respectively. We observed significantly increased frequency of RP genotype in casesas compared to controls (OR=1.87, 95% CI, 1.01-3.46, p=0.05). The frequencies of genotype A1A1, A1A2 andA2A2 of PIN3 ins16bp polymorphism were 69.12 vs 70.59%, 27.20 vs 25% and 3.68 vs 4.41% among patientsand controls. There was no significant difference among genotype and allele distribution between patients andcontrols. The frequencies of genotype GG, GA and AA of r.13494g>a polymorphism were 62.50 vs 64.70%, 34.56vs 30.15% and 2.94 vs 5.15% among patients and controls respectively. No significant difference between genotypeand allele frequency was observed in the patients and controls. For p.P47S and p.R213R polymorphisms, allthe cases and controls had homozygous wild type genotype. The RP-A1A1-GG genotype combination showssignificant risk for EC (OR=2.01, 95%CI: 1.01-3.99, p=0.05). Conclusions: Among the five TP53 polymorphismsinvestigated, only p.R72P polymorphism may contributes to EC susceptibility.