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。     

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。     

EBV相关胃癌与P53基因异常的研究

[目的]探讨EBV感染和p53基因异常在胃癌发生发展中的病因学作用.[方法]应用免疫组化技术检测13例EBV相关胃癌(EBV associated gastric carcinoma,EBVaGC),45例临床指标与之匹配的EBV阴性胃癌(EBV negative gastric carcinoma,EBVnGC)以及58例相应癌旁组织中p53蛋白的表达;PCR-SSCP银染技术检测p53基因exon 5～8突变情况.[结果]①胃癌组p53蛋白阳性率为86.2%(50/58),而相应癌旁组织均为阴性,胃癌组p53蛋白的阳性率明显高于癌旁组织组,两组间有极显著性差异(P=0.0000).②EBVnGC p53蛋白阳性率为86.7%(39/45),过表达率为57.8%(26/45);EBVaGC p53蛋白阳性率为84.6%(11/13),过表达率仅为15.4%(2/13).两组间p53蛋白的阳性检出率无明显差异(P=0.7912),但EBVaGC组p53蛋白过表达率明显低于EBVnGC组,两组间有显著性差异(P=0.0085).③2例EBVnGC检测到p53基因突变,突变均位于exon 5,13例EBVaGC和58例相应癌旁组织均未检测到p53基因突变.[结论]p53基因异常与胃癌的发生密切相关,EBVaGC组织中存在p53蛋白的表达和过表达,但p53蛋白的异常累积可能并非p53基因突变所致.     

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。     

EBV相关性胃癌罕见p53基因突变的可能机制与意义

2014年癌症基因组图谱（The Cancer Genome Atlas,TCGA）首次将胃癌从分子水平分为四型,其中EB病毒（Epstein-Barr virus,EBV）感染型即EBV相关性胃癌（EBV-associated gastric cancer,EBVaGC）患者,可能是免疫治疗的适宜群体。在包括胃癌在内的大部分肿瘤中p53基因突变率最高,但在EBVaGC中p53基因突变率却远低于EBV阴性胃癌（EBV-negative gastric cancer,EBVnGC）。可能机制为:EBV感染是EBVaGC形成的早期事件;野生型p53蛋白与病毒即刻早期蛋白BZLF1（Z）相互作用,维持EBV潜伏感染状态和早期复制;病毒复制后期,野生型p53蛋白可在病毒产物的作用下通过泛素化等途径被降解,以上或可表明p53基因野生型对EBVaGC形成的重要性。而EBV感染诱导炎症反应,肿瘤组织中大量淋巴细胞浸润,基因组高突变率及PD-L1扩增的特征使其可能成为免疫治疗的适宜群体,也说明免疫微环境在肿瘤发生发展中的重要作用。而在EBVnGC中,多种因素导致p53基因突变率较高,使其失去正常的抑癌功能而导致肿瘤发生。本文就EBVaGC中罕见p53基因突变这一现象的可能机制进行综述。      

IL-17基因多态性与胃癌易感性的关系

目的 探讨白介素-17（Interleukin-17,IL-17）基因rs2275913、rs763780多态性与胃癌易感性的关系。方法 收集青岛地区355例汉族胃癌患者为胃癌组,同期进行健康体检的300名正常者为对照组,采集两组患者外周血,提取全血基因组DNA,PCR扩增目的基因片段,采用DNA直接测序法检测IL-17基因rs2275913、rs763780位点基因型,分析其位点多态性与胃癌易感性的关系。结果 胃癌组与对照组IL-17基因 rs2275913位点基因型分布差异有统计学意义（χ²=17.192,P＜0.001）。与GG基因型相比,携带AA基因型的个体胃癌发病风险增加,差异有统计学意义（χ²=16.829,P＜0.05;OR=2.891,95%CI=1.721~4.857）;携带GA基因型的个体胃癌发病风险增加,但差异无统计学意义（χ²=0.878,P＞0.05）。胃癌组与对照组相比,IL-17基因 rs763780位点基因型分布差异无统计学意义（χ²=1.381,P=0.501）。结论 IL-17基因 rs2275913 A等位基因的携带会增加青岛地区汉族人群胃癌发病风险,IL-17基因 rs763780位点多态性与胃癌发病风险无明显相关性。     

EBV相关性胃癌中EB病毒基因表达研究进展

EB病毒（Epstein-Barr virus,EBV）是胃癌发生的生物学病因之一,EBV相关性胃癌（EBV associated gastric carcinoma,EB-VaGC）具有独特的临床病理学特征,其预后相对较好,因此EBV导致胃癌的机制研究也备受关注。近年来,随着分子生物学技术的发展,EBVaGC组织中EBV病毒基因表达的研究逐渐增多,为EBVaGC的诊断、治疗和预防提供了一定的理论依据。本文就EBVaGC组织中EBV病毒基因的表达进行综述。      

EB病毒相关胃癌与mdm2，p53及p21基因异常的研究

 目的 探讨p53基因突变以及mdm2，p53和p21蛋白表达异常在EBV相关胃癌（EBVaGC）发生发展中的作用。方法 应用免疫组化技术检测13例EBVaGC、45例临床病理资料与之匹配的EBV阴性胃癌（EBVnGC）组织中 mdm2，p53和p21蛋白的表达；PCR-SSCP银染技术结合DNA序列分析检测p53基因exon 5~8突变；RT-PCR检测EBV相关基因的表达。结果 E-BVaGC组与EBVnGC组相比，两组间mdm2，p53和p21蛋白的阳性检出率差异无统计学意义（P = 0.830 0；P = 0.791 2；P = 0.353 1），但EBVaGC组p53蛋白过表达率（15.38 %）明显低于EBVnGC组（57.78 %），两组间差异有统计学意义（P = 0.008 5）。mdm2蛋白阳性表达与p53蛋白过表达呈显著正相关（P = 0.000 8，r = 0.439 1）；p21与p53蛋白共同表达率较高，但经计数资料相关性统计学分析表明两者无显著相关性（P = 0.2501，r = 0.202 5）。2例EBVnGC检测到p53基因突变，突变均位于exon 5，13例E-BVaGC和58例相应癌旁组织均未检测到p53基因突变。13例EBVaGC核抗原基因EBNA1均为阳性，潜伏膜蛋白基因LMP1均为阴性，即刻早期基因BZLF1，早期基因BARF1和BHRF1阳性率分别为46.15 %（6／13），46.15 %（6／13）和15.38 %（2／13），三者与EBVaGC组织中mdm2，p21和p53蛋白的表达均无显著相关性（P＞0.05）。 结论 EBV感染以及mdm2，p53和p21蛋白表达异常与胃癌发生有关； p53基因突变可能并非胃癌组织中p53蛋白异常累积的主要原因；胃癌组织中EBV感染与p53蛋白的异常表达有关，而与mdm2和p21蛋白的异常表达以及p53基因突变无显著相关性。     

DNA修复基因RAD52 miRNA靶序列单核苷酸多态性与肝细胞癌遗传易感性研究

目的 探讨DNA修复基因RAD52 3'非翻译区（3'- untranslated region,3'-UTR）miRNA靶序列单核苷酸多态性（single nucleotide polymorphism,SNP）与广西地区人群肝细胞癌（hepatocellular carcinoma,HCC）遗传易感性的关系。方法 采用病例- 对照研究,对1 002例确诊的HCC新发病例和1 013例非肿瘤患者RAD52基因3'-UTR区域miRNA靶序列SNPs （rs1051669、rs1051672、rs7301931和rs7310449）进行基因分型,并分析其基因型频率分布及其与HCC遗传易感性的关系。结果 RAD52基因各SNP基因型在病例组和对照组中的分布频率差异均无统计学意义（P>0.05）。调整年龄、性别、吸烟、饮酒和HBV感染等因素后,未发现各SNP与HCC易感性有关联;分层分析发现,在女性人群中,与携带rs1051669 C等位基因相比,TT基因型可显著降低个体罹患HCC的风险（TT vs CT/CC：OR=0.03,95%CI：0.00~0.62,P=0.03）;与携带rs1051672 G等位基因相比,AA基因型可显著降低个体罹患HCC的风险（AA vs GA/GG：OR=0.03,95%CI：0.01~0.88,P=0.04）。结论 RAD52基因3'- UTR区域miRNA靶序列SNPs rs1051669、rs1051672位点可能与广西地区女性人群HCC易感性有关。     

中国人群PSCA基因rs2976392多态位点与胃癌易感性Meta分析

目的 评价前列腺干细胞抗原（prostate stem cell antigen，PSCA）基因rs2976392多态位点与中国人群胃癌易感性的关联。方法 通过计算机检索中国知网、万方数据库、维普数据库、NCBI、Embase、Web of Science等数据库获取关于胃癌与PSCA基因rs2976392多态位点相关的文献，检索时间为自建库起至2020年3月22日。对纳入文献进行质量评价后，使用RevMan 5.3和Stata 12.0软件进行Meta分析。 结果 最终纳入13篇文献共14项病例对照研究，包含6 618例胃癌患者和6 952例对照者。Meta分析显示，等位基因模型（A vs G）、显性基因模型（AA+GA vs GG）和1个共显性基因模型（AA vs GG）均显示PSCA基因rs2976392多态位点与中国人群胃癌发病风险增加有关（OR=1.28，95%CI：1.08~1.52，P=0.004；OR=1.35，95%CI：1.27~1.45，P＜0.001；OR=1.51，95%CI：1.03~2.20，P=0.030）。亚组分析结果显示，所有基因模型均与汉族人群胃癌发病风险增加有关（均P＜0.001），但与藏族人群胃癌发病风险无关（均P＞0.05）。 结论 PSCA基因rs2976392多态位点与中国人群胃癌发病风险升高有关，且以纯合AA基因型汉族人群的胃癌发病风险最高。     

Involvement of Toll-like receptors in cervical cancer susceptibility among Tunisian women

Previous studies underscored the importance of genetic factors in the pathogenesis of certain cancers, including cervical cancer. Epidemiological evidence supports an association between specific polymorphisms of Toll-like receptors (TLR) with several human pathological states, including cervical cancer. The aim of this study was to investigate the link between specific gene variants in TLR2 (-196 to -174 del), TLR3 (c.1377 C>T), TLR4 (Asp299Gly), and TLR9 (2848 G>A) and susceptibility to cervical cancer in Tunisian women. Study subjects comprised 122 women with histopathologically-confirmed cervical cancer, and 260 unrelated age- and ethnically-matched healthy females, who served as controls. TLR genotyping was done using PCR-restriction fragment length polymorphism. The C/C genotype of TLR3 (c.1377 C>T) is associated with cervical cancer susceptibility (OR: 1.71, CI: 1.08-2.70). For TLR4 (Asp299Gly), the Asp/Asp genotype and the Asp allele were associated with higher risk of developing cervical cancer (OR: 4.95, CI: 1.97-13.22) and (OR: 5.17, CI: 2.11-13.50) respectively. We demonstrated no association between the TLR2 (-196 to -174 del) and the TLR 9 (2848 G>A) polymorphisms and the susceptibility of cervical cancer among Tunisian women. However, the C/C genotype for the TLR3 (c.1377 C>T) polymorphism and the Asp/Asp genotype and the Asp allele for (Asp299Gly) TLR4 polymorphism were found to be associated with a higher risk of cervical cancer.     

Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) in Acute Myeloid Leukemia Patients

Backgrounds: Toll-like receptors 2; 4 (TLR2;4) are an essential component of the innate immunity and play an important role in immune-surveillance and immune response to various microorganisms. This study aimed to investigate the association between TLR2 and TLR4 polymorphism and the risk of acquiring severe infections, and impact on AML patient’s outcome. Subjects and methods: Using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP); we analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) in 120 AML patients and 100 healthy control subjects. Results: No significant differences in genotype or alleles frequency between healthy controls and AML patients regarding TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms (P>0.05 for all). Neutropenic fever was detected in 110 out of 120 (91.7%) of the studied AML patients. The sepsis and pneumonia were identified in 20 out of 120 patients (16.7%). The incidence of sepsis was associated with TLR2 Arg753Gln: AG genotypes, A allele and TLR4 Asp299Gly: CT genotype and C allele as compared to other genotypes and alleles. Moreover; TLR2 (Arg753Gln) GG polymorphisms significantly associated with shortest overall survival (OS) and shortest disease-free survival (DFS); while TLR4 polymorphisms affect the DSF only but not OS. In AML patients TLR2 Arg753Gln gene polymorphism is associated with high susceptibility to sepsis and TLR4 (Asp299Gly and Thr399Ile) gene polymorphism is associated with high susceptibility for both pneumonia; and sepsis. Conclusion: TLR2 Arg753Gln (AG; GG genotype) polymorphisms are associated with shortest OS and DFS. Moreover; significant association between TLR2 polymorphisms, TLR4 Arg753Gln polymorphisms and risk of severe infections in AML patients was documented.     

Association study of a functional Toll-like receptor 4 polymorphism with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma

Toll-like receptor 4, as part of innate immune response, is the main receptor for lipopolysaccharide on marginal zone B cells. The rare allele of TLR4 Asp299Gly attenuates receptor signaling and diminishes the inflammatory response. We genotyped 87 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, 594 Helicobacter pylori positive controls and 358 healthy blood donors to investigate an association of TLR4 Asp299Gly in the development of gastric MALT lymphoma. Heterozygote genotype was significantly less frequent in patients with gastric MALT lymphoma compared to H. pylori-infected controls (4.6% vs. 11.6%, Fischer's exact P = 0.019, odds ratio = 0.37, 95% confidence interval 0.13 - 1.03). Because 10% of caucasians are carriers of the rare allele G TLR4 Asp299Gly appears to be only one factor in the genetic susceptibility to gastric lymphoma. Further studies in larger samples are needed to confirm our findings and fully elucidate the role of TLR4 and its genetic variants in the pathophysiology of H. pylori infection and gastric lymphoma.     

Evaluation of Toll-Like Receptors 2/3/4/9 Gene Polymorphisms in Cervical Cancer Evolution

Accumulative epidemiological evidence suggests that polymorphisms of Toll-like receptors signaling pathway elucidated the cellular and molecular mechanisms of human diseases whose gaining a primordial importance. The aim of our study is to identify the role of TLR 2 (?196 to ?174 del), TLR 3 (1377 C>T), TLR 4 (Asp299Gly) and TLR 9 (G2848A) gene polymorphisms with the evolution of cervical cancer in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer and unrelated healthy female controls of similar ethnicity. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR 2, Ins/Ins genotype is a protector factor [p = 0.006; OR: 0.35(0.16–0.73)] and the dominant genotype of TLR 3 increased the risk of CC in stage (III+IV); C/C versuss C/T [p = 0.033; OR: 2.03(1.00–4.13)] and C/C versus C/T+T/T [p = 0.036; OR: 1.93(1.00–3.74)]. For TLR 4, the dominant genotype Asp/Asp is implicated in the occurrence of CC in stage (I+II) [p = 0.000; OR: 4.55(1.58–13.06)], [p = 0.001; OR: 3.49(1.44–8.45)] and in stage (III+IV) [p = 0.038; OR: 3.77(0.87–16.29)], [p = 0.007; OR: 5.21(1.65–16.46)] and the major allele Asp is a risk factor for the development of tumor in stage (I+II). The TLR2 Ins/Del genotype is associated with tumor evolution to stage (III+IV) [p = 0.003; OR: 3.00 (1.22–7.35)] and the genotypes Gly/Gly and Asp/Gly+Gly/Gly and Gly allele of TLR 4 are implicated in tumor evolution to the advanced stages. Further, TLR 2, TLR 3, TLR 4 and TLR 9 gene polymorphisms are implicated in the modulation of CC risk due to tobacco usage and statue of menopause among cases. Our study suggests a relationship between the incidence of the TLR2, TLR 3, TLR 4 and TLR9 mutations and the clinical progression of CC according to the FIGO classification. However, future studies with different demographic and clinical characteristics in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.     

CARD15/NOD2, CD14, and toll-like receptor 4 gene polymorphisms in Greek patients with sarcoidosis

BACKGROUND: Sarcoidosis, similarly to Crohn's disease (CD), is a complex inflammatory disease of unknown etiology. The belief that a genetic susceptibility to the development of sarcoidosis exists was derived from observations of familial clustering of sarcoidosis cases and racial differences in disease prevalence. Taking into account the remarkable similarity in the immunopathophysiology of sarcoidosis and CD, and in further exploring the genetic background of sarcoidosis, we study gene polymorphisms known for their implication in CD. These polymorphisms are in the CARD15/NOD2 gene (R702W, G908R and 3020insC), as well as mutations in the promoter of the CD14 gene (T/C at position -159) and in the TLR4 gene (Asp299Gly and Thr399Ile). METHODS: DNA was obtained from 100 sarcoidosis patients and 150 healthy individuals. Genotyping was performed by allele specific PCR or by PCR-RFLP analysis. RESULTS: Although CARD 15/NOD2 mutations were more frequent in cases than in controls, the difference was significant only for the G908R polymorphism (p = 0.024). Interestingly, the same was recorded with reference to the T allele (p = 0.002) and TT genotype (p = 0.017) frequencies of the CD14 promoter. No differences were observed in the 299Gly and 399Ile allele frequencies between patients and controls. Finally, the co-existence of a mutation in the CARD15/NOD2 and the CD14 genes was associated with sarcoidosis at a higher level of significance than any of these mutations separately. CONCLUSION: Our results suggest that the G908R mutation of the CARD15/NOD2 gene, as well as the T allele and TT genotype of the CD14 promoter are associated with increased susceptibility for developing sarcoidosis.     

Toll-like Receptor 4 Gene Polymorphisms and Susceptibility to Bladder Cancer

Bladder cancer is one of the most common malignancies in the world. Toll-like receptor 4 (TLR4) plays important roles in regulating innate immunity and may affect the development of cancers. Polymorphisms in TLR4 gene have been shown to be associated with impaired immune responses. Here, we investigated the association of TLR4 polymorphisms with bladder cancer. Four TLR4 polymorphisms (-2242T/C, Asp299Gly, Thr399Il3, and +3725G/C) were genotyped in a total number of 436 bladder cancer patients and 522 healthy controls. Data were analyzed using the Chi-square test. Results showed that the prevalence of TLR4 +3725GC and CC genotypes were significantly increased in bladder cancer cases than in controls (odds ratio [OR]?=?1.58, 95 % confidence interval [CI]?=?1.19–2.10, p?=?0.0015, and OR?=?2.33, 95%CI?=?1.52–3.58, p?<?0.0001, respectively). Also, the frequency of TLR4 +3725C allele was significantly higher in bladder cancer patients (p?<?0.0001). The -2242T/C, Asp299Gly and Thr399Il3 polymorphisms did not reveal any significant differences between cases and controls. Stratification analysis of the clinical features in the patients demonstrated that cases with invasive cancer were correlated with higher numbers of +3725GC and CC genotype (p?=?0.0004 and p?=?0.0231). In conclusion, these results indicate that TLR4 +3725G/C polymorphism may be a novel risk factor for bladder cancer in the Chinese population.     

GHR基因单核苷酸多态性与广西肝癌家系遗传易感性的研究

目的 探讨生长激素受体（growth hormone receptor,GHR）基因单核苷酸多态性（single nucleotide polymorphism,SNP）与广西扶绥县肝癌家系遗传易感性的关系。方法 选取广西扶绥县25个肝癌家系和17个健康对照家系人群为研究对象,其中肝癌家系肝癌患者25例（肝癌家系肝癌组）、非肝癌者81名（肝癌家系非肝癌组）;健康对照家系80名（对照组）。采用飞行时间质谱技术检测GHR基因rs6451620位点基因型及等位基因分布频率,非条件logistic回归模型分析rs6451620位点多态性与肝癌遗传易感性的关系。结果 GHR基因rs6451620位点存在G和A两种等位基因,AA、GA、GG 3种基因型。GHR基因rs6451620位点基因型频率符合遗传平衡。GHR基因rs6451620位点等位基因G和A在肝癌家系肝癌组中的分布频率分别为64%和36%,肝癌家系非肝癌组为60.5%和39.5%,对照组为70.6%和29.4%。以肝癌家系肝癌组和非肝癌组人群为研究对象时,携带A等位基因型的个体发生肝癌的风险是G等位基因型个体的0.81倍（95%CI：0.27～2.41,P=0.699）,以肝癌家系肝癌组和健康对照人群为研究对象时,携带A等位基因型个体发生肝癌的风险是G等位基因型个体的1.49倍（95%CI：0.73～3.04,P=0.274）。结论 GHR基因rs6451620位点单核苷酸多态性与广西肝癌家系遗传易感性无明显相关性。