MDM2基因多态性与肝细胞肝癌易感性的关系研究

目的:探讨小鼠双微体基因(murine double minute 2,MDM2)单核苷酸多态性(SNP)与肝细胞肝癌易感性及生物学行为的关系。方法:对166例肝癌病例和157例健康对照病例的外周血标本,利用SYBRGREEN PCR溶解曲线法分析MDM2基因型。结果:实验组等位基因的发生率(T,0.49;G,0.51)与对照组基因的发生率(T,0.59;G,0.41)(P=0.015)有统计学差异。肝癌患者中GG基因型的发生率(22.29%)高于健康人群(13.38%)(P=0.010)。结论:与TT基因型相比,携带G等位基因或GG型与肝癌发生的相关性较大。     

COX-2基因单核苷酸多态性与肝细胞癌关联的研究

目的:探讨广西地区COX-2基因-1195G>A(rs689466)和8473T>C(rs5275)位点单核苷酸多态性与肝细胞癌(HCC)遗传易感性的关系。方法:采用以医院为基础的病例对照研究方法。研究对象为780例经组织学确诊的HCC患者和780例相同地区、年龄、性别和民族频数匹配的非肿瘤患者。运用Taq Man MGB探针等位基因分型技术进行COX-2基因单核苷酸多态性的检测,以χ2检验和非条件Logistic回归模型分析比较病例和对照两组间各位点基因型频率分布的差异及其与HCC患病风险的关系,并进一步探讨基因-环境的交互作用对HCC患病风险的影响。结果:COX-2基因单位点-1195G>A或8473T>C多态与HCC患病风险无统计学相关性(显性模型下SNP-1195G>A:校正OR=1.32,95%CI:0.94~1.85;SNP8473T>C:校正OR=0.87,95%CI:0.64~1.18)。分层分析显示,显性模型下COX-2基因-1195G>A位点GA+AA基因型增加年龄<55岁者患HCC的风险(校正OR=1.56,95%CI:1.03~2.37),而8473T>C位点TC+CC基因型可降低女性患HCC的风险(校正OR=0.50,95%CI:0.25~0.99)。进一步交互作用分析显示,COX-2基因-1195G>A位点与年龄、8473T>C位点与性别分别存在交互作用(P=0.002;P=0.007)。结论:COX-2基因-1195G>A或8473T>C位点SNP的单独效应可能与HCC易感性无关联,但是-1195G>A与年龄、8473T>C位点与性别存在交互作用,影响HCC的患病风险。     

TIM-3基因多态性与肝细胞癌的关联性研究

目的:分析TIM-3 rs4704853、rs1036199和rs10515746基因多态性是否与肝细胞癌（HCC）易感性存在关联。方法:纳入HCC患者342例,健康对照组350例。采用血液基因组提取试剂盒（离心柱法）提取全基因组DNA。SNP分型采用多重扩增及高通量测序技术,采用多元Logistic回归方法分析TIM-3基因多态性与HCC易感性的关联性;采用多个独立样本秩和检验分析TIM-3基因多态性与HCC临床指标的关联。结果:TIM-3基因rs4704853、rs1036199和rs10515746存在完全连锁不平衡,以上3个SNP位点杂合子（OR=6.378,95%CI=1.414~28.776,P=0.016）或突变等位基因（OR=6.270,95%CI=1.396~28.165,P=0.017）患肝癌风险增加,且杂合子组血清TBA（总胆汁酸）水平明显高于野生纯合子组（P＜0.05）。结论:TIM-3 rs4704853、rs1036199和rs10515746基因多态性可能与HCC的发生和TBA水平具有关联性。     

MDM2 T309G基因多态性与前列腺癌的相关性

目的:探讨鼠双微体基因2(MDM2) T309G基因多态性与前列腺癌相关性。方法:用酚氯法提取全基因组DNA,应用聚合酶链反应、限制性内切酶的方法检测100例前列腺癌患者和100例健康男性的MDM2 T309G基因多态性。结果:病例组中G、T等位基因型频率分别为52.5%、47.5%,对照组中G、T等位基因型频率分别为40.5%、59.5%,MDM2 T309G基因型在两组的分布有显著性差异,TT基因型在对照组分布频率明显增高（P＜0.05）。结论:MDM2 T309G基因型在病例组和对照组的分布存在明显差异,G等位基因与前列腺癌发病增加相关。     

MDM2基因SNP309多态性与宫颈癌的相关性研究

目的：研究汉族妇女中MDM2基因SNP309多态性与宫颈癌易感性及临床病理学参数之间的关系。方法：用DNA抽提试剂盒从研究对象的外周血标本中抽提基因组DNA, 其中宫颈癌患者105例, 正常对照组140例; 用聚合酶链式反应-限制性片段长度多态 （PCR-RFLP） 和直接测序方法测定MDM2-SNP309单核苷酸多态基因型。结果：宫颈癌患者的MDM-SNP309 G等位基因频率显著高于对照组 （60.0% vs 48.6%, P=0.012; OR=1.59, 95% CI=1.11～2.28）; 宫颈癌与对照组之间的GG、 TG和TT等位基因型的分布差异有统计学意义, 其中GG等位基因型在宫颈细胞癌中的频率显著高于对照组 （36.2% vs 18.6%, P=0.016; OR=2.58,95% CI=1.19～5.61）。在宫颈癌组中, 淋巴转移阳性组MDM2-SNP309 GG等位基因型显著高于淋巴转移阴性组 （31.8% vs 11.5%, P<0.05）, SNP309单核苷酸多态性分布与肿瘤组织学类型、病理分级及肿瘤大小无关。结论:MDM2基因SNP309 GG基因型是宫颈癌发生的遗传易感因素, 与宫颈癌的淋巴转移发生有相关性。     

MET基因单核苷酸多态性与336例肝细胞癌患者术后生存期关联分析

目的 探讨MET基因单核苷酸多态性(SNP)与肝细胞癌术后患者总生存期(OS)的关联.方法 选取广西医科大学附属肿瘤医院2004-06-01-2013-12-31接受肝细胞癌根治术治疗的336例患者为研究对象,使用Sequenom Mass Array法对MET基因的4个SNP位点(rs121 A>G、rs38840 ...     

鼠MDM．2SNP309位点与肝细胞癌发病年龄与风险关系的分析

目的：探讨广西地区人群鼠双微粒体-2基因（MDM-2）启动子区309位点单核苷酸多态性（SNP）与肝细胞癌（hepatocellularcarcinoma,HCC）发病年龄和发病风险的关系。方法：运用聚合酶链反应一限制性片段长度多态性方法,对985例HCC病例扣992例非肿瘤对照者的MDM-2SNP309位点（T〉G,rs2279744）基因型进行检测,并分析该SNP与HCC发病年龄和发病风险的关系。结果：经年龄、性别、民族、吸烟、饮酒、HBV及HCV感染等因素校正后,MDM-2SNP309位点与HCC发病风险之间无统计学关联（TGWTT：OR-1．19,95％CI：0．86～1．65;GGwTT：OR-1．28,95％CI：0．89～1．85;TG＋GG＇USTT：OR-1．22,95％CI：0．90～1．66）。在女性HCC患者中,与携带MDM-2sNP309位点TG＋GG基因型的女性HCC患者相比（44．8岁）,携带TT基因型的女性患者HCC发病年龄提前4．6岁（49．4岁）,Logrank检验：x2=7．372,P=0．007。在男性患者中未发现此类似结果。结论：MDM-2SNP309位点多态性可能对HcC的发病风险无单独效应作用,但其TT基因型可能与女性HCC的发病年龄提前有关联。本研究结果需要大样本量的研究进一步验证。     

MDM2 启动子区309 位点基因多态性与乳腺癌风险的关系*

目的:采用病例- 对照研究检测MDM2 启动子区309 位点T>G 单核苷酸多态（SNP 309）在中国女性人群中的频率分布,分析其与中国女性乳腺癌发病风险的关系。方法:提取病例组698 例原发性乳腺癌患者及对照组525 例健康人的外周血单核细胞DNA,采用聚合酶链反应- 限制性片段长度多态性（PCR-RFLP ）分析法,检测MDM2 启动子区309 位点基因多态性,确定此位点三种基因型,即T/T、T/G、G/G 基因型。统计分析病例组和对照组人群MDM2 SNP 309 各基因型频率分布,及各基因型与乳腺癌发病风险的相关性。结果:在研究的病例组与对照组整体人群中,经年龄、月经状态、家族史及生育史等因素校正后,与MDM2 SNP 309 T/T基因型比较,T/G 型及G/G 型与乳腺癌的发病风险无显著相关性（T/G,adjusted OR= 1.2,95%CI:0.8～1.6,P=0.30;G/G,adjusted OR= 1.0,95%CI:0.7～1.5,P=0.88）。 进一步分层分析后显示:在绝经后人群中,与T/T基因型比较,T/G 基因型及G/G 基因型显著增加乳腺癌的发病风险（T/G,adjusted OR= 1.8,95%CI:1.2～3.0,P=0.011;G/G,adjusted OR= 1.9,95%CI:1.2～3.3,P=0.014）。 提示绝经后人群携带T/G 型、G/G 型者比携带T/T基因型者患乳腺癌的风险分别升高约1.8、1.9 倍。在绝经前人群中,各基因型与乳腺癌的发病风险无显著相关性（P>0.05）。 结论:MDM2 启动子309 位点突变型G 等位基因携带者显著增加绝经后女性乳腺癌的发病风险。      

IFN-γ基因多态性与HBV感染及原发性肝细胞癌易感性的研究

目的探讨细胞因子IFN-γ基因-1615C/T和+5171A/G位点单核苷酸多态性在广西人群中的分布及其对原发性肝细胞癌(HCC)发生、乙型肝炎病毒(HBV)感染的影响。方法设计以医院为基础的病例对照研究,对375名HCC患者、377名HBV携带者和406健康对照进行频数匹配,采用TaqMan MGB实时荧光定量PCR技术对上述位点进行分型。应用Logistic回归模型分析基因型在三组中的分布差异及基因环境交互作用,并进行连锁不平衡和单倍型分析。结果-1615C/T和+5171A/G位点的基因多态性在三组中分布差异无统计学意义(P＞0.05)。Logistic回归分析结果显示,吸烟、饮酒和肝癌相关家族史与基因存在交互作用;饮酒联合-1615C/T位点突变型基因T能增加HBV感染风险(OR=1.72,95%CI:1.11~3.26);两个位点的突变型基因T和G联合肝癌相关家族史能增加HCC患病风险（OR:29.24、52.03,95%CI:6.91~123.6、7.02~385.4）。IFN-γ的-1615C/T和+5171A/G位点存在连锁不平衡(D′=0.976,P=2.22^-16),但单倍型分布在HCC组与总对照组（HBV携带者对照和健康对照）间无统计学差异。 结论IFN-γ的-1615C/T和+5171A/G位点的突变型基因可能不是广西人患HCC和感染HBV的直接危险因素,但环境危险因素对HCC发生和HBV感染有协同作用。     

MDM2启动子309位点多态性与乳腺癌易感性关系的Meta分析

[目的]综合评价MDM2（routine double minute2）基因启动子309位点多态性与乳腺癌易感性的关系。[方法]检索中国医学文献数据库和PubMed中MDM2基因SNP309与乳腺癌易感性关系的病例对照研究,并用Meta分析的方法合并SNP309与乳腺癌易感性OR值。然后进行其中有家族史的乳腺癌亚组分析,敏感性分析和文献的发表偏倚检验。[结果]Meta分析共纳入10篇文献,乳腺癌家族史组有3篇;累计病例7535例,对照8272例,G等位基因相对于T等位基因0R值为1．01（95％CI：0．96～1．06）。乳腺癌家族史组G等位基因相对于T等位基因OR值为1．06（95％CI：0．94～1．19）。[结论]MDM2基因309T〉G多态与乳腺癌易感性无统计学意义。     

MDM2 rs2279744 polymorphism and endometrial cancer: a meta-analysis

Case–control studies on the association between mouse double minute 2 homolog (MDM2) rs2279744 polymorphism and endometrial cancer have provided either controversial or inconclusive results. To clarify the effect of MDM2 rs2279744 polymorphism on the risk of endometrial cancer, a meta-analysis of all case–control observational studies was performed. Pooled odds ratios (ORs) for various polymorphisms were estimated using random and fixed effect models. Q-statistic was used to evaluate the homogeneity, and Egger and Begg tests were used to assess publication bias. Overall, the MDM2 rs2279744 polymorphism was associated with a risk of endometrial cancer (OR?=?0.76; 95 % CI?=?0.64–0.90 for allele contrast, p?=?0.002, P _het?=?0.003). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast. In the analysis stratified by ethnicity, significant associations were found in the Caucasian population in all of the genetic models. Our pooled data suggest evidence for a major role of MDM2 rs2279744 polymorphism in the carcinogenesis of endometrial cancer, especially among Caucasian populations.     

Murine double minute 2 rs2279744 polymorphism and hepatocellular carcinoma risk in East Asians: a meta-analysis

Murine double minute 2 (MDM2) is a crucial negative regulator of p53 function through several mechanisms. There are many studies performed to assess the association between MDM2 rs2279744 polymorphism and hepatocellular carcinoma risk, but the impact of MDM2 rs2279744 polymorphism on hepatocellular carcinoma in East Asians is unclear owing to the inconsistent findings from previous studies. We conducted a comprehensive meta-analysis of epidemiological studies to shed some light on these contradicting results. We used pooled odds ratio (OR) with its 95 % confidence intervals (95 % CI) to assess the association. Overall, seven studies with a total of 4,993 subjects were finally included. The meta-analysis suggested that MDM2 rs2279744 polymorphism was significantly associated with increased risk of hepatocellular carcinoma in East Asians (G versus T: OR?=?1.27, 95 % CI 1.06–1.52, P?=?0.01; GG versus TT: OR?=?1.59, 95 % CI 1.11–2.27, P?=?0.01; GG/GT versus TT: OR?=?1.41, 95 % CI 1.07–1.87, P?=?0.02; GG versus TT/GT: OR?=?1.32, 95 % CI 1.08–1.62, P?=?0.008). Sensitivity analysis by excluding low-quality study still suggested that the association above was still significant. Thus, the findings from the meta-analysis support that MDM2 rs2279744 polymorphism is significantly associated with increased risk of hepatocellular carcinoma in East Asians.     

Association between KIF1B rs17401966 polymorphism and hepatocellular carcinoma risk: a meta-analysis involving 17,210 subjects

Some publications have evaluated the correlation between KIF1B rs17401966 polymorphism and hepatocellular carcinoma (HCC) with conflicting results. We performed this meta-analysis to clarify the association of KIF1B rs17401966 polymorphism and HCC risk. We searched PubMed, ISI Web of Knowledge, ScienceDirect, and Google Scholar. The combined odds ratio (OR) with 95 % confidence interval (CI) was calculated to estimate the strength of the association. Heterogeneity and publication bias were also assessed. In total, 15 case-control studies with 7,596 HCC cases and 9,614 controls were included in the meta-analysis. A significant association between KIF1B rs17401966 polymorphism and HCC risk was detected (OR?=?0.81, 95 % CI 0.72–0.91, P?KIF1B rs17401966 polymorphism and HCC risk in Chinese (OR?=?0.77, 95 % CI 0.67–0.89, P?KIF1B rs17401966 polymorphism was significantly associated with HCC risk in man (OR?=?0.57, 95 % CI 0.51–0.64, P?P?P?P?=?0.11). This meta-analysis showed a significant association between KIF1B rs17401966 polymorphism and HCC.     

MDM2基因多态与肝癌遗传易感性的Meta分析

目的:根据已发表的相关文献,综合评估鼠双微体同源基因2(MDM2)多态与肝癌遗传易感性之间的关系。方法:按照统一的检索策略在相关中英文数据库中全面检索相关文献,对文献进行筛选、评价后获得相关研究的结果数据,然后应用Stata 10软件中Meta分析的方法,计算合并OR值及95%CI,并进行敏感性分析和发表偏倚的估计。结果:共有国内外5篇合格文献纳入本研究,累计病例和对照数分别为738和1 062例。合并结果显示,携带GG等位基因型者患肝癌的危险性是携带TT等位基因型的2.39倍(95%CI=1.81～3.15,P<0.001),携带TG等位基因型者患肝癌的危险性是携带TT等位基因型的1.65倍(95%CI=1.31～2.08,P<0.001)。发表偏倚评估未发现明显的偏倚。结论:MDM2SNP309多态中GG、TG等位基因型可能与肝癌的易感性升高有关。     

Association between the rs2910164 polymorphism in pre-mir-146a and oral carcinoma progression

MicroRNAs are short non-coding RNAs that regulate gene expression by RNA interference. Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. miR-146a has been reported to regulate Toll-like receptors and cytokine signaling, which are both crucial for inflammation and oncogenesis. This study identifies that areca nut extract, TNFα and TGFβ up-regulates miR-146a in OSCC cells. The increased expression of miR-146a enhanced the oncogenicity of OSCC cells. In addition, a G to C polymorphism (rs2910164), which is located in the pre-miR-146a and has been associated with functional alterations in miR-146a, was significantly more prevalent among OSCC patients having more advanced nodal involvement. Our analysis also suggested a higher miR-146a expression in OSCC tissues of patients carrying C polymorphism. The present study concluded a higher prevalence of the pre-mir-146a C-variant was associated with OSCC progression in patients with this disease.     

MDM2 SNP309T>G polymorphism and hepatocellular carcinoma risk: a meta-analysis

Case–control studies on the association between mouse double-minute 2 homolog (MDM2) SNP309T>G polymorphism and hepatocellular carcinoma have provided either controversial or inconclusive results. To clarify the effect of MDM2 SNP309T>G polymorphism on the risk of hepatocellular carcinoma, a meta-analysis of all case–control observational studies was performed. Pooled odds ratios (ORs) for various polymorphisms were estimated using random and fixed effects models. The Q-statistic was used to evaluate the homogeneity, and Egger and Begg tests were used to assess publication bias. Overall, the MDM2 SNP309T>G polymorphism was associated with a risk of hepatocellular carcinoma (OR?=?0.68; 95 % CI?=?0.54–0.85 for allele contrast, p?=?0.0005, p _het?=?0.004). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast. In the analysis stratified by ethnicity, significant associations were found in the Caucasian population in all of the genetic models. In addition, heterogeneity disappeared in subgroups of Caucasian subjects. Our pooled data suggest evidence for a major role of MDM2 SNP309T>G polymorphism in the carcinogenesis of hepatocellular carcinoma, especially among Caucasian populations.     

miRNA-146a rs2910164基因多态性与肝癌易感性的Meta分析

目的系统评价miRNA-146ars2910164基因多态性与肝癌易感性之间的相关性。方法全面检索PubMed、Excerpta Medica Database（Embase）、中国生物医学文献数据库（Chinese Biomedical Literature Database,CBM）、the Cochrane Library、维普、谷歌学术和万方数据库,文献检索起止时间均为从建库至2013-11。搜集研究miRNA-146a rs2910164基因多态性与肝癌相关性的文献。对miRNA-146ars2910164G/C各基因型比较模型,包括G与C、GG与CC、GG与GC、GC与CC、GG＋GC与CC以及GG与GC＋CC,在病例组和对照组的分布情况进行定量综合分析。结果共纳入9篇文献,共有2 951例肝癌及3 217名健康对照。miRNA-146ars2910164基因多态性与肝癌易感性之间具有相关性,GG与CC比较的OR=1.21,95%CI为1.04～1.42,P=0.02;GC与CC比较的OR=1.15,95%CI为1.02～1.29,P=0.02;GG＋GC与CC比较的OR=1.16,95%CI为1.04～1.29,P=0.009。亚组分析结果发现,在亚洲人群中也有相似的结论,GC与CC比较的OR=1.15,95%CI为1.02～1.29,P=0.02;GG＋GC与CC比较的OR=1.16,95%CI为1.04～1.30,P=0.009。结论 miRNA-146ars2910164基因多态性与肝癌易感性之间具有相关性,并且miRNA-146a rs2910164基因多态性的CC基因型可能是肝癌的保护因素。     

PD-1基因多态位点rs2227982和rs10204525与肺癌关联性分析

目的:PD-1基因是肿瘤免疫调节的关键靶点,本研究探讨PD-1基因的多态性位点（rs2227982 和rs10204525）与肺癌发生的关系。方法:应用病例对照研究的方法,收集肺癌患者302例和健康对照320例,采用Taqman Genotyping方法对收集的样本进行基因分型,并分析其与临床特征关系。结果:发现携带rs2227982 C等位基因,增加肺癌发病风险［OR=1.31,95%CI（1.03~1.64）］（P=0.019）,基因型分析发现在相加性模型(additive model)［OR=1.30,95%CI（1.04~1.62）］和隐性模型(recessive model)［OR=0.62,95%CI（0.42~0.97）］中与肺癌发生具有相关性。进一步通过调整吸烟、年龄和饮酒的影响后,rs2227982基因型仍与肺癌发生显著相关［OR=1.38,95%CI（1.08~1.77）］,P＜0.001。但rs2227982基因型与肺癌的病理类型和临床分期无关联,研究结果未发现rs10204525基因型与肺癌发生相关。结论:PD-1基因多态性与肺癌发生相关,rs2227982-CC基因型人群的肺癌发病率高于rs2227982-CT和rs2227982-TT基因型,通过多中心及大样本的验证,可作为潜在的遗传易感性分子标记。     

Association between the p53 codon 72 Arg/Pro polymorphism and hepatocellular carcinoma risk

Previous studies regarding the association of p53 codon 72 Arg/Pro polymorphism with hepatocellular carcinoma (HCC) risk have provided conflicting and inconclusive findings. Thus, a meta-analysis of all currently available publications was performed to address this issue. Eleven individual case–control studies involving a total of 2,718 cases and 3,752 controls were identified after a systematic search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association of p53 codon 72 Arg/Pro polymorphism with HCC risk was estimated by the pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI). Subgroup analyses stratified by ethnicity, source of controls, gender, hepatitis virus infection status, and family history of HCC were also conducted to assess the association. Overall, significantly increased risk of HCC was identified among carriers of the homozygous genotype ProPro (OR_{ProPro vs. ArgArg}?=?1.38 (95 % CI, 1.03–1.85), P _OR?=?0.033; OR_{ProPro vs. ArgArg + ArgPro}?=?1.28 (95 % CI, 1.03–1.59), P _OR?=?0.026). In subgroup analysis by ethnicity, the pooled results suggested that the p53 codon 72 Arg/Pro polymorphism was associated with an increased risk of HCC in Asians and Caucasians (for Asians, OR_{ProPro vs. ArgArg + ArgPro}?=?1.17 (95 % CI, 1.02–1.34), P _OR?=?0.025; for Caucasians, OR_{ProPro vs. ArgArg}?=?1.65 (95 % CI, 1.07–2.56), P _OR?=?0.025; OR_{ProPro vs. ArgArg + ArgPro}?=?1.74 (95 % CI, 1.14–2.66), P _OR?=?0.010). Subgroup analyses by source of controls and hepatitis virus infection status further demonstrated the significant association, whereas stratification factors involving gender and family history of HCC did not modify the association between p53 codon 72 Arg/Pro polymorphism and HCC risk. This meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism may play a critical role in the development of HCC, and gender and family history of HCC may not modulate the effect of p53 codon 72 Arg/Pro in HCC risk.