Toll样受体2基因多态性与胃癌及EB病毒相关胃癌易感性的关系

目的:探讨Toll样受体2(TLR2) rs3804099和rs3804100基因多态性与胃癌和EB病毒相关胃癌(EBVaGC)易感性的关系。方法:选用185例EBV阴性胃癌(EBVnGC)组织、41例EBVaGC组织以及100位健康人群外周血标本作为研究对象,采用PCR结合限制性片段长度多态性(RFLP)技术检测TLR2 rs3804099与rs3804100的基因多态性。结果:TLR2 rs3804099基因型和等位基因频率在胃癌组与健康对照组间的差异均有统计学意义(χ²=5.617,P=0.018;χ²=6.467,P=0.011),胃癌组C等位基因频率及C等位基因携带者频率均明显高于健康对照组(χ²=6.467,P=0.011;χ²=4.444,P=0.035),且与野生TT型相比,CC基因型可增加胃癌的发病风险(OR=3.554, 95%CI=1.179~10.715)。TLR2 rs3804100位点的各基因型频率、C等位基因及C等位基因携带者的频率在胃癌组和健康对照组之间差异无统计学意义(P>0.05)。TLR2 rs3804099与rs3804100位点的各基因型频率、C等位基因频率及C等位基因携带者频率在EBVaGC和EBVnGC两组间的差异均无统计学意义(P>0.05)。结论:TLR2 rs3804099基因多态性可能与胃癌发病风险有关,C等位基因可能为胃癌的危险因子,携带C等位基因可能增加胃癌的发病风险。TLR2 rs3804099与rs3804100基因的多态性与EBVaGC的易感性无明显相关性。     

Toll样受体基因多态性与EBV感染相关胃癌的易感性

目的： 探讨Toll样受体(TLR)家族成员TLR2基因启动子区-196~-174 del和TLR4基因 Thr399Ile位点多态性与EBV相关胃癌(EBVaGC)及EBV阴性胃癌(EBVnGC)易感性的关系。方法：采用PCR技术检测52例EBVaGC,157例EBVnGC以及94例正常对照人群TLR2(-196~-174 del)基因多态性;PCR-限制性片段长度多态性(PCR-RELP)技术检测50例EBVaGC,67例EBVnGC以及71例正常对照TLR4 Thr399Ile位点基因型及等位基因分布;分析2种基因多态性与EBVaGC及EBVnGC易感性的关系。结果：胃癌组与对照组比较TLR2(-196~-174 del)基因型分布无显著差异(χ2=3.180,P=0.075),胃癌组del等位基因频率明显高于对照组(χ2=4.875, P=0.027),del等位基因携带者的罹患危险性明显高于非携带者(OR=1.491,95%CI=1.045~2.126);EBVaGC组和EBVnGC组中,TLR2(-196~-174 del)3种基因型以及del等位基因频率差异无统计学意义(χ2=0.05,P=0.867)。EBVaGC组、EBVnGC组和正常对照组中均未发现TLR4基因Thr399Ile位点的多态,其基因型分布及等位基因频率差异均无统计学意义(P>0.05)。结论：TLR2(-196~-174 del)等位基因可能是胃癌发病危险因素,且在EBVaGC和EBVnGC两种胃癌发生中产生相同的影响。未发现TLR2(-196~-174 del)和TLR4基因Thr399Ile基因型分布与EBVaGC的易感性相关。     

青岛地区汉族人群中lncRNA H19 的多态性与胃癌和EBV相关胃癌易感性的关系

[摘要] 目的：探讨青岛地区汉族人群lncRNA H19 单核苷酸多态性（SNP）与胃癌和EBV相关胃癌(EBVaGC)易感性的关系。方法：收集青岛地区汉族人群2015 年1 月至2018 年10 月青岛大学附属医院经病理科确诊为胃癌的新鲜组织或陈旧的石蜡包埋胃癌组织病理标本共225 例,为胃癌组;依据原位杂交法对EBV编码的小分子非多聚腺苷酸(EBER1)转录检测结果再将胃癌组分为2 亚组：EBVaGC 组70 例,EBVnGC组155 例;同时选择青岛大学附属医院门诊健康体检者200 例为对照组。提取EBVaGC、EBVnGC 组织及健康人群外周血标本的DNA,根据HaploView 软件常规设置原则（MAF>0.05;r2>0.8）筛选出rs217727、rs2735971、rs2839698 和rs3741216 四个H19 的TagSNPs。利用Taq-Man MGB 等位基因分型试剂盒对各SNP位点基因进行基因分型,并进行基因多态性检测。结果：所取标本的H19 SNPs 均符合Hardy-Weinberg 平衡。与对照组比较,胃癌组H19 rs217727位点TT 基因型的发病风险显著增加(χ2=9.073, P=0.003, OR=1.999, 95% CI=1.271～3.143),等位基因T 的分布也明显增高(χ2=13.475, P=0.001, OR=1.661, 95% CI=1.266～2.180);H19 rs2839698 位点TC、CC基因型人群可显著增加胃癌的发病风险(χ2=9.407,P=0.002; χ2=6.517, P=0.011),携带C等位基因人群罹患胃癌的风险明显增加(χ2=6.163, P=0.013, OR=1.417, 95% CI=1.076~1.867;χ2=9.542, P=0.02, OR=2.070, 95% CI=1.298~3.302)。但胃癌组H19 rs2735971 和rs3741216 位点基因多态性与对照组比较差异不明显（均P>0.05）;EBVaGC 和EBVnGC 组中H19 的4 个位点基因多态性分布差异均无统计学意义（均P>0.05）。结论：H19 rs217727、rs2839698 基因多态性可能与胃癌发病风险有关,携带TT 基因型C等位基因和人群胃癌的发病风险明显升高;H19 SNP的多态性与EBVaGC的发病风险无明显相关。     

凋亡基因Caspase3和Caspase7单核苷酸多态性与胃癌遗传易感性研究

目的 Caspase家族的SNP在乳腺癌、头颈部肿瘤、食管癌、肺癌等癌症中研究较多,而Caspase3,7的SNP与中国人群胃癌发病风险之间的研究较少。本实验旨在利用大样本研究Caspase3和Caspase7基因的SNP与胃癌遗传易感性的关系。方法 收集东北地区胃癌病例1 000例、对照组1 036例血液标本,进行基因组DNA提取。根据NCBI的dbSNP数据库和HapMap数据库,对Caspase 3,7选择潜在的SNP位点,所选位点均位于Caspase3,Caspase7的3′UTR。对Caspase 3,7的SNP位点运用Taqman探针法进行基因型分型。病例对照之间不同变量构成比差异采用双侧χ²检验,对每个位点进行Hardy-Weinberg遗传平衡检验后,采用χ²检验比较病例组和对照组的单个位点基因型频率差异,再通过单因素和多因素Logistic回归模型分析基因型与疾病的关联,对每个位点分层分析比较不同性别、年龄、吸烟、饮酒状况亚层之间基因型与疾病的关联。结果 病例组与对照组的吸烟、饮酒状态以及年吸烟包数(Pack-years)构成存在统计学差异(P＜0.05)。所选位点基因型频率符合Hardy-Weinberg遗传平衡定律(P＞0.05)。将带有风险等位基因的基因型组合后进行分析,显示出针对两个基因来说,带有两个风险基因型的个体比带有0~1个风险基因型的个体患病风险增加了69.6%,调整了协变量影响后带有3个风险基因型的个体比带有0~1个风险基因型的个体患病风险增加了27.6%,带有大于1个风险基因型的个体比带有0~1个风险基因型的个体患病风险增加了35%。两个基因组合之后的分层分析中,年龄≤60岁、男性、从不吸烟、年吸烟包数≤25、胃非贲门腺癌的亚层中风险基因型与疾病有统计学关联,即具有更显著的危险性。结论 本研究所选取的四个位点的SNP均与胃癌风险无关。但通过多因素分析Caspase3、Caspase7的四个位点,带有2个风险基因型比带有0~1个风险基因型的个体患病风险增加。此外,通过分层分析Caspase7的两个位点,其在年龄≤60岁,从不吸烟,年吸烟包数≤25包和非胃贲门腺癌人群中患病风险更为明显。     

TLR4 Thr399Ile基因多态性与胃癌易感性的研究

目的:探讨Toll样受体4（toll-like receptor 4,TLR4）Thr399Ile基因多态性与胃癌易感性的关系。方法:通过计算机检索及手工检索,收集有关TLR4 Thr399Ile基因多态性与胃癌易感性的文献,筛选出符合纳入和排除标准的文献,应用Meta分析软件对各项研究进行异质性检验,计算合并OR值及其95％CI,并行敏感性分析和发表偏倚的评估。结果:8篇文献纳入本研究,共计有1297例胃癌患者和2702例对照人群。TLR4 Thr399Ile基因多态性与胃癌易感性的研究结果为:T versus C:OR=1.307,95%CI=1.047-1.631;TT versus CC:OR=1.527,95%CI＝0.398-5.860;TC versus CC:OR=1.324,95%CI＝1.049-1.670;TT/TC versus CC:OR=1.326,95%CI＝1.053-1.671;TT versus TC/CC:OR=1.481,95%CI＝0.386-5.685。根据种族来源进行分层分析,在高加索人群中的研究结果为:T versus C:OR=1.298,95%CI＝1.027-1.640;TC versus CC:OR=1.313,95%CI＝1.027-1.679;TT/TC versus CC:OR=1.316,95%CI＝1.031-1.679。结论:TLR4 Thr399Ile TC、TT/TC基因型及T等位基因能增加胃癌的患病风险。     

端粒酶逆转录酶基因多态性与胃癌遗传易感性的研究

目的探讨端粒酶逆转录酶（TERT）基因rs2736098 和 rs2736100位点单核苷酸多态性与胃癌遗传易感性和幽门螺杆菌（Hp）感染的关系。方法 采用限制性片段长度多态性聚合酶链反应（PCR RFLP）检测297例胃癌患者（病例组）和306例非萎缩性胃炎患者（对照组）中TERT基因rs2736098和rs2736100位点的多态性;采用病理学诊断和13C尿素酶呼气试验检测Hp感染。结果 rs2736098位点各基因型频率在病例组和对照组中的分布差异无统计学意义（P＞0.05）,病例组rs2736100位点仅GG基因型频率显著高于对照组（27.0％ vs. 16.4％,P＜0.05）。Logistic回归分析显示,携带GG基因型个体罹患胃癌的风险是携带TT基因型个体的1.371倍（OR=1.371,95％CI：1.063～1.775,P=0.005）;在Hp阴性者中,GG型罹患胃癌的风险较TT型增加（OR=1.421,95％CI：0.988～2.042,P=0.046）;而在Hp阳性者中,未发现rs2736100位点的基因型与罹患胃癌的风险有关。结论 TERT基因rs2736100位点基因多态性可能与胃癌遗传易感性相关,而与Hp感染无关。     

细胞因子基因多态性和胃癌易感性

免疫性细胞因子及其基因多态性检测已成为胃癌临床遗传流行病学研究的一个热点.研究发现,部分细胞因子基因多态性单独或与幽门螺杆菌(HP)联合增加胃癌或癌前病变的风险.     

白细胞介素4基因内含子3多态性与贲门癌和非贲门胃癌的易感性关系

目的 探讨白细胞介素4（IL-4）基因内含子3多态性与中国福建省贲门癌、非贲门胃癌遗传易感性的关系。方法 采用序列特异性引物聚合酶链式反应（PCR-SSP）法和Sanger测序法检测中国福建省100例贲门癌、130例非贲门胃癌和113例慢性萎缩性胃炎患者（对照组）的IL-4基因内含子3的多态性,并分析其多态性与贲门癌、非贲门胃癌发病风险的相关性。结果 贲门癌组、非贲门胃癌组的上消化道肿瘤（UGIC）家族史阳性个体的比例高于对照组。UGIC家族史可同时增加贲门癌和非贲门胃癌的发病风险（OR=2.738,95％CI：1.220～6.143;OR=2.452,95%CI：1.122～5.361）。IL-4内含子3的3种基因型（RP1.1、RP1.2、RP2.2）频率在贲门癌组、非贲门胃癌组和对照组中的总体分布差异有统计学意义（P＜0.05）;与RP1.1基因型比较,携带RP1.2基因型可增加非贲门胃癌的发病风险（OR=2.111,95％CI：1.172～3.803）。分层分析显示,与RP1.1基因型相比,RP1.2基因型能增加男性（OR=2.496,95％CI：1.235～5.047）和UGIC家族史阴性（OR=1.909,95％CI：1.020～3.573）非贲门胃癌的发病风险;而携带RP2.2基因型可使家族史阴性非贲门胃癌的发病风险降低（OR=0.496,95％CI：0.268～0.918）。结论 IL-4内含子3基因多态性可能是影响中国福建省非贲门胃癌发病风险的因素之一。     

MTHFR基因遗传多态与食管癌贲门癌易感性的关系

目的:探讨食管癌高发区亚甲基四氢叶酸还原酶(MTHFR)基因单核苷酸多态与食管癌、贲门癌发病风险的关系。方法:以聚合酶链反应和限制性片段长度多态方法,分析584例食管癌患者、467例贲门癌患者和540例正常对照的MTHFR基因C677T基因型及其与食管癌、贲门癌发病风险的相关性。结果:在正常对照中,MTH-FR677CC、CT、TT基因型频率分别为22.1%、43.3%和34.6%,在食管癌患者中分别为12.5%、45.0%和42.5%(P=0.000);在贲门癌患者中分别为15.8%、43.5%和40.7%(P=0.024)。多因素分析发现,携带677TT基因型和677CT基因型的个体发生食管癌的风险分别是677CC基因型的2.36倍和1.76倍,发生贲门癌的风险分别是1.34倍和1.23倍。结论:MTHFR单核苷酸多态是食管癌高发区食管癌和贲门癌的遗传易感性因素。     

FAT10单核苷酸多态性与肝细胞癌发生发展的关联

目的探讨FAT10基因外显子和侧翼序列单核苷酸多态性（single-nucleotide polymorphism,SNP）与 肝细胞癌发生和临床病理的关系。方法通过DNA测序分析方法,检测254例肝癌和268例健康对照人群的FAT10基因SNPs,并比较不同基因型与肝细胞癌的发生和临床病理的的关系。采用Haploview统计软件分析研究对象的连锁不平衡和单体型。结果在肝癌组和对照组共检测到10个SNPs位点。 其中-143 A/G,-121 A/G,+3476 T/C,+3607 T/C,+3620 C/G和 +3809 G/T基因型与相应的野生型纯合子相比能明显降低肝癌发病的风险（P<0.05）,但是这些多态性位点的基因型频率与肝癌的临床表型无关（P>0.05）。进一步单体型分析发现,各变异等位基因在病例组和对照组内均存在遗传连锁不平衡现象,AATTTCG、AATCTCG、GGCTCGT和AGCTCGT为四种常见的单体型。GGCTCGT和AGCTCGT单体型可能对肝癌的发病起保护性效应（OR=0.41,95%CI:0.24~0.70,P<0.05 和OR=0.43,95% CI:0.22~0.983,P<0.05）,而AATTTCG单体型可能增加肝癌的发病风险（OR=1.64,95% CI:1.24~2.17,P<0.05）。结论本研究首次发现中国汉族人群FAT10基因外显子和侧翼序列SNPs与肝癌的易感性相关,但需要不同种族的大样本和功能研究进一步验证。     

Meta-analysis of Associations between Interleukin-17 Gene Polymorphisms and Risk of Gastric Cancer

Background: Previous studies have indicated that single nucleotide polymorphisms (SNPs) of the interleukin-17(IL-17) gene are associated with an increased risk of gastric cancer. However, the findings were inconsistent.Materials and Methods: To provide a more reliable estimation of the association between SNPs in the IL-17gene and the susceptibility to gastric cancer, we searched PubMed, CNKI, and Wan Fang databases and selectedfinally six studies covering 2,366 cases and 3,205 controls to perform a meta-analysis. Results: Statistical analysesshowed that an rs2275913 polymorphism within the IL-17A gene was significantly associated with an increasedrisk of gastric cancer using a generalized odds ratio (ORG, a model-free approach). Moreover, we also found thatthe ‘A’ allele carriers of IL-17A rs2275913 had a significant link with clinicopathological features. However, nosignificant positive signals were observed in the association analysis of the rs3748067 and rs763780 polymorphismswith the risk of gastric cancer in IL-17A and IL-17F, respectively. Conclusions: Despite some limitations, thepresent meta-analysis provided a more precise estimation of the relationship between the IL-17 gene SNPs andgastric cancer risk compared with individual studies.     

Lack of Influence of an XRCC3 Gene Polymorphism on Oral Cancer Susceptibility: Meta-analysis

Background: To systematically summarize the association between the X-ray repair cross complementing3 (XRCC3) gene polymorphism and oral cancer susceptibility by meta-analysis. Materials and Methods:Databases including PubMed, EMbase, CNKI, VIP and WanFang Data were searched to identify case-controlstudies concerning the association between an XRCC3 gene polymorphism and the risk of oral cancer from theinception to June 2014. Two reviewers independently screened the literature according to the criteria, extractedthe data and assessed the quality. Then meta-analysis was performed using Stata 11.0 software. Results:Seven published case-control studies including 775 patients with oral cancer and 1922 controls were selected.Associations between the rs861539 polymorphism and overall oral cancer risk were not statistically significantin all kinds of comparison models (CT vs CC: OR=0.94, 95%CI=0.74-1.18; TT vs CC: OR=0.94, 95%CI=0.64-1.38; dominant model: OR=0.95, 95%CI=0.76-1.18; recessive model: OR=0.94, 95%CI=0.69-1.29; allele T vs C:OR=0.97, 95%CI=0.84-1.11). In the stratified analysis by ethnicity, no significant associations were found amongAsians and Caucasians. On stratification by tumor type, no significant associations were found for cancer andoral premalignant lesions. Conclusions: The XRCC3 gene polymorphism was not found to be associated withthe risk of oral cancer. Considering the limited quality of the included case-control studies, more high qualitystudies with large sample size are needed to verify the above conclusion.     

Manganese Superoxide Dismutase (MnSOD Val-9Ala) Gene Polymorphism and Susceptibility to Gastric Cancer

Background: Oxidative stress caused by the generation of reactive oxygen species plays an important rolein human carcinogenesis. Manganese superoxide dismutase (MnSOD) Val-9Ala in the mitochondrial targetsequence is the best known polymorphism of this enzyme. The purpose of the current research was to assess theassociation of MnSOD Val-9Ala genotypes with the risk of gastric cancer. Materials and Methods: This casecontrolstudy covered 54 gastric cancer patients compared to 100 cancer free subjects as controls. Extractionof DNA was performed on bioptic samples and genotypes were identified with a polymerase chain reactionrestrictionfragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MnSOD Ala/Ala,Ala/Val and Val/Val genotypes in healthy individuals were 24.3, 66.7 and 9%, respectively. However, in gastriccancer patients, Ala/Ala, Ala/Val and Val/Val were observed in 24.0, 48.0 and 28.0% (p=0.01). In patients thefrequency of MnSOD Val allele was higher (52%) compared to that in controls (42%). Conclusions: The resultsof this study show a positive association between MnSOD Val-9Ala gene polymorphism and risk of gastric cancerdisease in Iranian population.     

Evaluation of Insulin Like Growth Facror-1 Genetic Polymorphism with Gastric Cancer Susceptibility and Clinicopathological Features

Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancerdeaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have beenassociated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth,proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatoryelements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigatethe influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for thefirst time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controlswere recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragmentlength polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statisticallyanalyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regressionanalysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition,no significant association between genotypes and clinicopathological features was observed (p value>0.05). Thefrequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%,2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. Thefrequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively.Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerfulgenetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.     

Association of Two CD44 Polymorphisms with Clinical Outcomes of Gastric Cancer Patients

Objective: CD44 is an important cell adhesion molecule that plays a key role in growth, invasion, proliferation andmetastasis of cancer cells. CD44 protein over-expression is associated with a poor prognosis of gastric cancer (GC) andprevious studies have shown that CD44 gene polymorphisms could affect survival and recurrence. In this study, wetested the hypothesis that polymorphisms impacting on the CD44 signaling pathway may predict clinical outcomes inpatients with GC. Materials and Methods: DNA was extracted from blood of 150 healthy individuals and formalin-fixedparaffin-embedded (FFPE) tumor tissue of 150 patients. The two polymorphisms rs187116 and rs7116432 werestudied by RFLP-PCR and sequencing techniques. Results: There was a strong significant correlation between singlenucleotide polymorphisms (SNPs) in the CD44 gene, tumor recurrence, and overall survival (p <0.0001). The existenceof a significant relationship between tumor recurrence and overall survival was proved in this study, with at least oneallele G for the polymorphism rs187116 and at least one allele A for polymorphism rs7116432. Conclusion: These resultsprovide evidence of a relationship between CD44 gene polymorphisms and clinical outcomes in our GC patients.This result could help identify individuals with GC who have a high risk of tumor recurrence.     

STAT4基因多态性与乙型肝炎病毒感染相关性肝细胞癌易感性的关系

目的 分析信号传导与转录激活因子4(STAT4)基因多态性与中国人群肝细胞癌(HCC)易感性的关系.方法 154例乙型肝炎病毒(HBV)感染相关HCC为肝癌组,135例性别及年龄匹配的HBsAg阳性患者为非肝癌组.采用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP),检测STAT4 rs7574865位点的基因型,并经测序分析验证.Logistic回归分析比较不同基因型与HCC易感风险的关系.结果 STAT4 rs7574865位点3种基因型TT、GT、和GG型在肝癌组的分布频率分别是5.8％ (9/154)、37.0％ (57/154)和57.1％ (88/154),在非肝癌组分别是8.9％(12/135)、43.7％ (59/135)和47.4％ (64/135).各基因型在两组间差异无统计学意义(P＞0.05);以TT基因型作参照,携带rs7574865 GG型的个体HCC患病风险差异无统计学意义(OR=1.833,95％ CI=0.729～4.611,P=0.221).结论 STAT4 rs7574865多态性位点可能与中国人群HBV感染相关HCC易感性无明显相关性.     

白细胞介素-12B基因多态性与胃癌遗传易感性的关系

[目的]研究白细胞介素（IL-12B）基因3’UTR（A1188C）位点多态性与江苏地区胃癌发生的关系。[方法]采用聚合酶链反应-限制性片段长度多态性（RFLP）分析法检测1045例胃癌新发病例和1100例与病例性别、年龄匹配的健康对照人群的IL-12B基因1188A／C位点多态性。[结果]IL-12B基因1188A／C位点基因多态性在正常人群和胃癌患者中的分布无显著性差异（P〉0．05）,但在饮酒的人群中,携带1188C等位基因可降低患胃癌的危险（OR=0．69,95％CI=0．47～0．99）。[结论]IL-12B基因1188A／C位点基因多态性可能与江苏地区饮酒人群胃癌的发生有关。