红细胞补体受体1单核苷酸多态性与肝细胞癌发病风险的研究

目的 探讨红细胞补体受体1（CR1）单核苷酸多态性（SNP）与肝细胞癌（HCC）发病的关系。方法 收集102例HCC患者（HCC组）和98例健康体检者（对照组）的外周血样本,选取CR1的5个标签SNP位点（rs4844600 G＞A、rs17048010 T＞C、rs3818361 C＞T、rs11118167 T＞C和rs9429945 C＞T）进行检测,分析两组的红细胞CR1基因各SNP位点基因型、等位基因及单体型的分布差异及其与HCC患病风险的关系。同时按照性别、年龄相匹配的原则分别从对照组和HCC组中选取52例和53例样本采用流式细胞术检测其红细胞CR1的几何平均荧光强度比值（GMFIR）。结果 两组rs4844600 G＞A基因型和等位基因分布的差异有统计学意义（P＜0.01）。CR1基因rs4844600 G＞A／GG基因型携带者患HCC的风险为非携带者的2.458倍（95％ CI：1.357～4.451）,GA基因型携带者患病风险是非携带者的0.404倍（95％CI：0.218～0.746）,其等位基因G携带者患病风险为非携带者的1.945倍（95％CI：1.183～3.199）。rs17048010 T＞C、rs3818361 C＞T、rs11118167 T＞C、rs9429945 C＞T这4个SNP位点和rs11118167-rs3818361-rs17048010／TCT、TTC、CCT、TTT这4种单体型与HCC的患病风险无关（P＞0.05）。HCC组CR1的GMFIR水平为3.257±1.191,高于HCC组的2.652±0.789,差异有统计学意义（t=2.644,P=0.008）。结论 HCC患者红细胞免疫功能降低,CR1基因SNP位点rs4844600 G＞A与HCC发病关联。     

Fas／FasL基因多态性与肝细胞癌易感性的关系

目的 探讨凋亡相关基因Fas及其配体FasL单核苷酸多态性（SNPs）与肝细胞癌（HCC）易感性的关系。方法 收集本院2013年1月至2016年12月经病理确诊的126例HCC患者的外周血标本,在Sequenom MassARRAY系统上利用基质辅助激光解吸电离飞行时间质谱法（MALDI-TOFMS）进行Fas多态性位点 rs1571013、rs1800682及rs1468063和FasL多态性位点rs6700734、rs763110的基因分型,选取130例健康体检者的外周血作对比,采用Hardy-Weinberg平衡分析以上5个SNPs位点的遗传平衡情况,比较HCC患者与健康对照rs1571013、rs1800682、rs1468063、rs6700734和rs763110基因型和等位基因的分布差异并计算比值比（OR）及其95%置信区间（95%CI）来评价以上SNPs与HCC易感性的关系。结果126例HCC患者及130例健康体检者的Fas多态性位点 rs1571013、rs1800682及rs1468063和FasL多态性位点rs6700734及rs763110基因型的分布符合Hardy-Weinberg平衡。HCC组与对照组rs1468063、rs6700734和rs763110基因型分布的差异无统计学意义（P＞0.05）,且与HCC易感性无关;rs1571013分布上,HCC组A／A基因型及等位基因A的比例均高于对照组（P<0.05）,其中以G／G基因型为参照,A／A基因型发生HCC的风险升高至2.492倍（P<0.05）,而A／G、A／G+A／A发生HCC的风险未改变（P＞0.05）,以G等位基因为参照,A发HCC的风险升高至1.549倍（P<0.05）。rs1800682分布上,HCC组G／G基因型及等位基因G的比例均高于对照组,差异有统计学意义（P<0.05）,以A／A基因型为参照,G／G基因型发生HCC的风险升高至2.880倍（P<0.05）,而A／G、A／G+G／G发生HCC的风险未改变（P＞0.05）;以A等位基因为参照,G发生HCC的风险升高至1.651倍（P<0.05）。 结论 Fas rs1571013、rs1800682与HCC易感性有关,其中携带突变等位基因的HCC发生风险升高,在HCC易感人群筛查中有一定价值。     

CD44基因多态性与宫颈癌及非小细胞肺癌的相关性

背景与目的：CD44分子是众多肿瘤细胞的标志分子，其表达水平与肿瘤细胞的恶性程度有关。该研究探讨CD44基因中的单核苷酸多态性（single nucleotide polymorphism，SNP）位点与云南汉族人群宫颈癌和非小细胞肺癌（nonsmall cell lung cancer，NSCLC）易感性的相关性。方法：选取了CD44基因中的两个SNP位点rs13347和rs8193，采用TagMan基因分型的方法，分析这两个多态性位点在497例宫颈癌患者和500例健康对照个体以及483例NSCLC患者和471例健康对照个体中的分布特征，并分析CD44基因中的多态性位点与云南汉族人群宫颈癌和NSCLC的相关性。结果：rs13347和rs8193位点等位基因和基因型在宫颈癌组和对照组中的分布频率的差异无统计学意义（P>0.05）。而在NSCLC组和对照组的比较中：rs13347和rs8193位点等位基因在NSCLC组和对照组中的分布频率的差异有统计学意义（P=0.020和P=0.004）；这两个位点基因型在NSCLC组和对照组中分布频率的差异有统计学意义（P=0.027和P=0.020）；其中rs13347位点等位基因C在NSCLC组中的分布频率显著高于对照组，可能是NSCLC发生的风险因素（OR=1.250，95% CI：1.035～1.509），rs8193位点等位基因C在对照组中的分布频率显著高于NSCLC组，可能是NSCLC发生的保护性因素（OR=0.768，95%CI：0.641～0.921）。单倍型分析结果显示，rs13347C-rs8193T和rs13347T-rs8193C在NSCLC组和对照组中的分布频率差异有统计学意义（P=0.003和0.022）；该结果说明单倍型rs13347C-rs8193T可能是云南汉族人群NSCLC发生的风险性因素（OR=1.316，95%CI：1.096～1.579）。结论：CD44基因中的两个SNP位点rs13347和rs8193可能与云南汉族人群宫颈癌发病风险无关，而可能与云南汉族人群NSCLC具有相关性。     

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。     

真核翻译起始因子3遗传变异与HBV相关肝细胞癌发病风险的相关性

目的 探讨真核翻译起始因子3(eukaryotic translation initiation factor 3,eIF3)遗传变异与乙型肝炎病毒相关肝细胞癌（HBV-HCC）发病风险的关系。方法 本研究采用两阶段病例对照研究的方法,发现阶段以广西的966例HCC病例和1 003例乙型肝炎病毒表面抗原（hepatitis B surface antigen,HBsAg）阳性对照为研究对象,筛选出与HCC发病风险有关联的单核苷酸多态性（single nucleotide polymorphisms,SNP）位点,验证阶段采用上海的480例HCC病例和484例HBsAg阳性对照人群对发现阶段的阳性位点进行验证。通过单因素和多因素logistic回归分析eIF3遗传变异位点与HBV-HCC发病风险的相关性。结果本研究发现EIF3G 3′-UTR区2个具有潜在功能的SNPs(rs7401 A>G和rs23057952 A>G)与HBV-HCC的发病风险相关。其中与A等位基因携带者相比,rs7401 G等位基因携带者的HBV-HCC发病风险增加（OR=1.18,95%CI:1.02...     

广西扶绥县壮族人群 ATF 5 基因多态性与肝癌家系遗传易感性的关系

目的:探讨广西扶绥县壮族人群ATF5基因rs283526和rs8647位点多态性与肝细胞癌(hepatocellular carcinoma,HCC)遗传易感性的关系.方法:采用病例-对照研究方法,选择广西扶绥县壮族人群HCC家系79例(观察组)、正常对照家系40例(对照组),运用质谱方法检测ATF5基因rs283526和rs8647位点基因型分布频率;应用非条件Logistic回归分析不同基因型与HCC发病风险的相关性.结果:对照组人群ATF5基因rs283526位点CT、TT基因型个体发生HCC的风险分别是CC基因型个体的0.181倍(95％ CI =0.440-0.736,P＜0.05)和0.348倍(95％ CI=0.151-0.804,P＜0.01)、rs283526位点携带T等位基因型的个体发生HCC的风险是C等位基因型个体的0.405倍(95％CI=0.226-0.726,P＜0.01).ATF5基因rs8647对照组人群GA、AA基因型个体发生HCC的风险分别是GG基因型个体的1.022倍和1.949倍,其携带A等位基因型的个体发生HCC的风险是G等位基因型个体的0.952倍,但差异均无统计学意义(P＞0.05).结论:广西扶绥县HCC家系ATF5基因rs283526多态性与肝癌遗传易感性有相关性,其等位基因T是HCC的保护因素.     

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。     

MMP-12和MMP-13基因启动子区功能性多态与喉癌遗传易感相关性研究

目的：探讨基质金属蛋白酶-12（matrix metaIIoproteinases-12,MMP-12）基因启动子区-82A／G和MMP-13基因启动子区-77A／G基因多态（single nucleotide polymorphism,SNP）与中国北方汉族人群喉鳞状细胞癌（1aryngeal squa—mous cell carcinoma,LSCC）发病易感性的相关性。方法：采用聚合酶链式反应-连接酶检测反应（PCR—LDR）技术检测148例LSCC患者和148例健康对照个体MMP-12—82A／G多态（rs2276109）、MMP-13-77A／G多态（rs2252070）的基因型。结果：患者组中MMP-12—82A／G多态的A、G等位基因频率（98．6％、1．4％）与对照组（93．6％、6．4％）相比差异有统计学意义,P=0．001;基因型频率分布与对照组相比差异有统计学意义,P=0．001;与A／A基因型相比,A／G基因型可显著增加喉鳞状细胞癌的发病风险,0R=5．30,95％CI：1．76～16．00。MMP-13—77A／G多态的A、G等位基因频率在患者组中为42．2％和57．8％,与对照组的32．4％和67．6％相比差异有统计学意义,P=0．01;但基因型频率分布与对照组相比差异无统计学意义,P=0．07。进一步分析发现,该遗传模型为显性遗传。结论：MMP-12—82A／G多态、MMP-13—77A／G多态与LSCC发病风险有关,-82G与-77A等位基因可能成为预测中国北方汉族人群喉鳞状细胞癌发病风险的独立危险因素。     

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。     

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。     

A genetic variant in the promoter of CD46 is associated with the risk and prognosis of hepatocellular carcinoma

CD46 (also known as membrane cofactor protein), which is a member of the membrane-bound complement regulatory protein family, has been reported to cause cancer cells to escape complement-dependent cytotoxicity. However, the association between CD46 polymorphisms and the risk of hepatocellular carcinoma (HCC) has not been investigated. This two-stage association study was conducted to assess the relationship between the tagging single nucleotide polymorphisms (tagSNPs) of CD46 and HCC risk and prognosis. A series of functional analyses were performed to study the underlying mechanisms. Among the eight tagSNPs, rs2796267 (P = .003) and rs2796268 (P = .011) were found to modify HCC risk in the discovery set. Only rs2796267 (P < .0001) was confirmed to be associated with HCC susceptibility in the validation set. Compared with the wild-type AA genotype, the GG genotype significantly increased the HCC risk (adjusted odds ratio [OR] = 2.03; 95% confidence interval [CI], 1.34-3.08; P = .001). Moreover, subgroups analysis suggested a positive correlation among male and younger patients, especially among drinkers, smokers, and hepatitis B surface antigen-positive individuals. In functional analyses, we found that the rs2796267 G allele in the promoter region of CD46 could increase the expression of CD46 by affecting the binding affinity of STAT5a. Furthermore, Cox regression analysis revealed that the rs2796267 AG/GG genotype was significantly associated with worse prognosis of resected patients with HCC (hazard ratio = 2.27; 95% CI, 1.27-4.05; P = .006). These results suggest that the CD46 rs2796267 polymorphism may contribute to susceptibility and prognosis of HCC by altering promoter activity.     

Genetic Polymorphism of Epidermal Growth Factor Gene as a Predictor of Hepatocellular Carcinoma in Hepatitis C Cirrhotic Patients

Background: In Egypt, the incidence of hepatocellular carcinoma (HCC) is approximately 4.7% of chronic liver disease patients due to (HCV) infection. Epidermal growth factor (EGF) plays an important role in hepatocyte regeneration. A functional polymorphism in EGF 61A>G was identified; itwas associated with higher risk of HCC. Objectives: to investigate the correlation between the epidermal growth factor (EGF) polymorphism and the risk of hepatocellular carcinoma (HCC) in hepatitis C viral (HCV) cirrhotic patients as well as its relation to EGF protein expression in HCC tissue. Patients and methods: this casecontrol study was conducted on 75 HCV cirrhotic patients including 50 HCC patients (25 withresectable HCC and 25 with advanced unresectable HCC) and 25 healthy persons were included. EGF genotype was detected by restriction fragment length polymorphism. EGF expression in HCC tissue biopsiesfrom patientswhounderwent surgical resection was done by immunohistochemical examination. Results: The GG genotype was associated with significant increased risk of HCC compared to AA genotypes (P=0.031) in cirrhotic group. The G allele had a highly significant risk of HCC compared to allele Ain recessive model GG vs. AG+AA (P=0.036) rather than in the dominant model GG +AG vs. AA (P=0.66). There was significant increased expression of EGF in tumour tissues in patients with GG genotype compared to AG genotype and AA genotype p= 0.019. Conclusion: EGF gene polymorphism (GG genotype) had a significant risk of HCC development in cirrhotic patients. This is confirmed by increased EGF expression in liver tumor tissue from HCC patients.     

Association of MicroRNA 196a and 499 Polymorphisms with Development of Cirrhosis and Hepatocellular Carcinoma Post-HCV Infection in Egyptian Patients

Hepatocellular carcinoma (HCC) is the commonest primary tumor of the liver. Chronic HCV infection is the leading cause of end-stage liver disease, HCC and liver-related death in Egypt. Single nucleotide polymorphisms (SNPs) in microRNAs were reported to increase susceptibility to tumorigenesis; affect prognosis and as promising biomarkers in virus-host interactions. This study was conducted to investigate the role of genetic variants of miR-196a2 (rs 11614913) C>T and miR-499 (rs 3746444) A>G in the development of cirrhosis and HCC in Egyptian HCV infected patients. Genotyping of the candidate SNPs was performed by Real Time PCR in 75 HCV-related HCC patients, 75 cirrhotic patients on top of HCV and 75 healthy controls. There was significant difference in miR-499 (rs3746444) genotypes frequency between the three studied groups as the GG genotype was significantly lower in HCC cases than other groups (P = 0.009) while the combined miR-499 (AA+AG) genotypes were significantly higher in HCC cases than other groups (P = 0.005). Also a significant difference was found in miR-499 genotypes frequency when compared between HCC and cirrhosis groups as the GG genotype was significantly lower in HCC cases than cirrhosis group (P = 0.006) while the combined miR-499 (AA+AG) genotypes were significantly higher in HCC cases than in cirrhosis group (P = 0.003) [OR (95% CI) = 0.131 (0.028-0.601)]. The frequency of the G allele was significantly lower in HCC than other groups (P = 0.024) and significantly lower in HCC than normal group (P = 0.006) [OR (95%CI) = 0.501 (0.304-0.825)]. For miR-196a2 (rs11614913) C>T polymorphisms, no significant association was found with HCC risk. Our study concluded that the G allele of miR-499 is associated with lower risk of HCV related HCC development. No significant association of miR-196a2 (rs 11614913), genotypes or alleles with risk for HCC development, could be detected.     

PLXNC1 多态性与广西肝癌遗传易感的关系及其表达*

目的:探讨PLXNC1 基因多态性与广西肝癌遗传易感性关系及表达。方法:以广西20个肝癌高发家族（肝癌家族组79例）和10个健康对照家族（健康对照组40例）为研究对象,应用飞行时间质谱技术检测两组中PLXNC1 基因rs 2272335 的基因型及等位基因频率,免疫组织化学染色检测PLXNC1 在不同肝组织中的表达。结果:PLXNC1 基因rs 2272335 位点健康对照组人群中携带C 等位基因型的个体发生干细胞肝癌（hepatocellularcarcinoma ,HCC ）的风险分别是T 等位基因型个体的4.16倍（95%CI 为0.37～47.3）,差异有统计学意义（P = 0.032）。核心成员组与 肝癌患者组两组间差异无统计学意义（P > 0.05）。PLXNC1 基因rs 2272335 位点基因型TT、TC、CC在肝癌患者组人群、核心成员组人群、健康对照组人群三组间者差异无统计学意义（P > 0.05）。 肝癌组织中,PLXNC1 蛋白表达水平3.12± 1.12显著高于肝癌癌旁组织1.54± 0.67和正常肝组织1.23± 0.87（P < 0.05）。结论:PLXNC1 基因rs 2272335 位点C 等位基因型可能是广西HCC 发生的危险因素。PLXNC1 过度表达与肝癌发生密切相关。      

Positive Association Between miR-499A>G and HepatocellularCarcinoma Risk in a Chinese Population

A case-control study of the association of miR-499A>G rs3746444 with risk of hepatocellular carcinoma(HCC)was conducted. Patients with HCC and healthy control subjects were recruited for genotyping of miR-499A>G using duplex polymerase-chain-reaction with confronting-two-pair primer(PCR-RFLP) analysis. TheMiR-499 GG genotype was associated with a decreased risk of HCC as compared with the miR-499 AA genotype(adjusted OR=0.74, 95%CI=0.24-0.96). Similarly, the GG genotype showed a 0.45-fold decreased HCC risk in arecessive model. The MiR-499 G allele was significantly associated with decreased risk of HCC among patientsinfected with HBV in a dominant model (OR=0.09, 95%CI= 0.02-0.29). In conclusion, the MiR-499A>G rs3746444polymorphism is associated with HCC risk in the Chinese population, and may be useful predictive marker forCAD susceptibility.     

基于Keap1基因多态性的肾透明细胞癌分子标志物的研究

目的:探讨KeapJ基因单核苷酸多态性与肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)的相关性,为临床诊疗提供有效的分子靶点.方法:采集ccRCC组织108例与正常对照肾组织86例,采用聚合酶链式反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)和基因测序技术检测KeapJ基因单核苷酸多态性,判读两组样本基因型,实时荧光定量PCR法检测Keap1基因在两组中的表达情况.结果:Keap1基因rs1048289的不同基因型与等位基因频率在肿瘤组和对照组之间的分布不同,差异均有统计学意义(P＜0.05).AA基因型及A等位基因携带者患肾透明细胞癌的风险明显升高,AA基因型(OR=2.292,95％ CI:1.159～4.533,P＜0.05)及A等位基因(OR =2.067,95％ CI:1.280 ～3.342,P=0.001)为肾透明细胞癌患病的危险因素.肿瘤组Keap1基因表达量比对照组明显降低(P＜0.05),但不同基因型样本间Keap1基因表达量无明显差异(P＞0.05).结论:Keap1基因rs1048289与肾透明细胞癌患病显著相关,有望成为肾透明细胞癌早期诊断与基因治疗的有效分子靶点.     

CTLA-4基因多态性与膀胱癌易感性的相关性及基因-环境交互作用的研究北大核心

目的:探讨细胞毒性T淋巴细胞抗原4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)基因rs733618、rs5742909、rs231775位点单核苷酸多态性与膀胱癌的相关性。方法:收集188例膀胱癌患者和188名健康对照人群的人口学及生活行为方式资料,采集研究对象5 mL外周血提取DNA,通过imLDR技术对rs733618、rs5742909、rs231775位点进行基因分型,观察各位点基因型在病例组和对照组之间的分布差异,使用条件Logistic回归分析各基因型与膀胱癌发病风险的关系,并基于GMDR探究基因与环境的交互作用。结果:CTLA-4 rs733618位点基因型和等位基因频率在病例组和对照组间的分布差异均无统计学意义(P>0.05);rs231775位点基因型和等位基因频率在两组的分布差异均有统计学意义(P<0.05),但rs733618、rs5742909、rs231775三个位点与患膀胱癌的风险关系均未达到统计学差异(P>0.05)。吸烟是膀胱癌的独立危险因素(OR=2.982,95%CI:1.594~5.577)。GMDR分析表明rs231775位点、吸烟史和文化程度间存在交互作用(OR=3.44,95%CI:1.82~6.53)。结论:CTLA-4基因rs733618、rs5742909、rs231775位点多态性与中国人群膀胱癌患病风险可能无关,其中rs231775位点与吸烟史及文化程度因素存在交互作用,增加膀胱癌患病风险。     

广西扶绥县人群DDX39基因单核苷酸多态性与肝癌家系遗传易感性的关系

目的 探讨广西扶绥县原发性肝细胞癌(hepatocellular carcinoma,HCC,以下简称“肝癌”)高发家系人群DDX39基因rs12461754位点单核苷酸多态性与肝癌遗传易感性的相关性。方法 选取广西扶绥县20个肝癌高发家系共77例和10个正常对照家系共35名为研究对象,采用基质辅助激光解析电离飞行时间质谱技术(matrix assisted laser desorption ionization-time of fight-mass, MALDI-TOF-MS)检测DDX39基因rs12461754位点在两组中的基因型和等位基因频率。结果 正常对照家系组人群DDX39 基因rs12461754 位点携带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0.407倍(95%CI:0.125~1.326,P=0.136);在肝癌高发家系非肝癌组人群中,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0.981倍(95%CI:0.298~3.326,P=0.976); DDX39基因rs12461754位点GG、AG、AA基因型在肝癌高发家系肝癌组、肝癌高发家系非肝癌组及正常对照家系组三组间相互比较,差异无统计学意义(P>0.05)。结论 DDX39基因rs12461754位点单核苷酸多态性与广西扶绥县肝癌家系遗传易感性无明显相关性。