白细胞介素8－251A/T单核苷酸多态性及其血浆水平与冠心病易感性的关系

目的研究白细胞介素8-251A/T单核苷酸多态性及其血浆水平与冠心病易感性的关系。方法应用聚合酶链反应限制片长多态性检测冠心病组与对照组白细胞介素8-251A/T单核苷酸多态性,酶联免疫吸附法测定白细胞介素8血浆水平。结果白细胞介素8血浆水平在冠心病组显著高于对照组(P<0.05),-251A/T基因型频率、等位基因A和T频率在两组间差异无统计学意义(P>0.05)。但是与其他冠心病患者相比,急性冠状动脉综合征患者AA基因型明显减少(OR=0.43,95%CI为0.2～0.97,P<0.05)。结论白细胞介素8血浆水平与冠状动脉粥样硬化病变有相关性。-251A/T位点单核苷酸多态性与冠心病无相关性,但可影响冠心病的临床表现。AA基因型或许能降低急性冠状动脉综合征的发病风险。     

胃癌白细胞介素-1β基因多态性与胃癌关系的荟萃分析

背景:随着胃癌病因研究的深入,目前发现许多宿主因素与胃癌的形成密切相关,白细胞介素(IL)-1β基因多态性成为重要的候选因素.目的:综合评价IL-1β-511等位基因及其基因型在胃癌发生中的作用,以期较深入地揭示IL-1β基因多态性与胃癌的关系.方法:共有7篇发表于1994年1月～2003年10月期间的有关IL-1β基因多态性与胃癌关系的国内外病例对照研究纳入荟萃分析,采用Review Manager 4.2统计软件对其结果进行定量综合分析.结果:以IL-1β-511位点的C/C基因型为对照,C/T、T/T和*/T基因型均为胃癌的危险因素,其OR值(95%CI)分别为1.78(1.51.2.10)、1.92(1.07～3.44)和1.79(1.54～2.07),但T/T基因型经敏感性分析后结果逆转.结论:IL-1β-511位点的C/T和*/T基因型是胃癌的危险因素,但T/T基因型与胃癌的关系尚未明确.     

白细胞介素2基因-330T/G和白细胞介素6基因-174G/C多态性与结核病易感性的Meta分析

目的 分析白细胞介素2(IL-2)基因-330T/G和IL-6基因-174G/C多态性与结核病易感性的关系。方法 在Medline、PubMed、EMBase、Web of Science、Elsevier Science Direct、万方数据库、中国知网(CNKI)和维普数据库中检索从1990年1月至2017年6月公开发表的关于IL-2和IL-6基因多态性与结核病易感性关系的中文和英文文献。初筛获得相关文献573篇,根据文献纳入和排除标准最终纳入文献12篇。应用Stata 12.0软件对各研究原始数据进行Meta分析。结果 IL-2基因-330T/G位点研究纳入文献共8篇,病例组971例,对照组1519名。Meta分析结果显示,欧洲人群中携带IL-2基因-330T等位基因者较携带-330G等位基因者患结核病风险低45%(T对G:OR=0.55;95%CI=0.31~0.98;P=0.042)。IL-6基因-174G/C位点纳入研究共9篇,病例组1445例,对照组1955名。Meta分析结果显示,美洲人群中携带IL-6基因-174G等位基因者患结核病风险是携带-174C等位基因者的1.65倍(G对C:OR=1.65;95%CI=1.28~2.13;P<0.01);亚洲人群中携带IL-6基因-174G等位基因者患结核病风险是携带-174C等位基因者的1.4倍(G对C:OR=1.40;95%CI=1.13~1.72;P=0.002)。结论 IL-2基因-330T/G位点等位基因T可能与欧洲人群结核病易感性风险降低相关;IL-6基因-174G/C位点等位基因G可能与美国人群和亚洲人群结核病易感性风险增加相关。     

白细胞介素-17F A7488G多态性与广东地区胃癌的关系

目的 分析白细胞介素(IL)-17F A7488G(p.His161Arg)多态性与广东地区胃癌遗传易感性及其与胃癌患者临床病理学特征和预后的关系.方法 采用聚合酶链反应-跟制性片段长度多态性(PCR-RFLP)法分析927例胃癌患者及777名健康对照者的IL-17F A7488G多态性,采用Logistic回归法和Cox比例风险法研究其对不同临床病理学特征的胃癌发病风险的影响并进行生存分析.结果 IL-17F A7488G基因型频率在胃癌患者与健康对照人群间差异有统计学意义(X2=16.55,P<0.01).与AA纯合子相比,IL-17F A7488G杂合变异基因型(GA)及纯合变异基因型(GG)显著增加胃癌的发病风险,OR值分别为1.51和1.61(95%CI分别为1.22～1.87和1.03～2.51,P值均<0.01).与AA携带者相比,携带G(GA或GG)等位基因者发生胃癌的风险显著增加(OR=1.53,95%CI:1.25～1.87,P<0.01).按临床病理特征行分层分析显示,IL-17F A7488GGA基因型与肠型、低中分化、非贲门癌、淋巴结转移等的发病风险增加有关.IL-17F A7488G不同基因型患者间生存率差异无统计学意义(P=0.534).结论 广东地区IL-17F A7488G多态性与胃癌易感性有关,IL-17F A7488G变异基因型增加胃癌的发病风险,但不是影响胃癌患者预后的危险因素.     

中国人白细胞介素-6基因多态性与动脉粥样硬化相关性的Meta分析

目的分析白细胞介素(IL)-6基因多态性与中国居民动脉粥样硬化(AS)发病风险的相关性。方法按照综合的检索策略在万方、CNKI、维普、Pubmed和Web of Science数据库中全面检索关于IL-6基因多态性与AS相关性的病例对照研究,应用Stata11.0进行Meta分析。结果最终15篇相关文献符合纳入排除标准。经过Meta分析,发现IL-6-174G/C多态性与AS无关;IL-6-572C/G多态性与AS显著相关:携带GC基因型个体患AS的危险性是CC基因型个体的1.68倍(95%CI=1.47~1.93,P<0.001);携带GG基因型个体患AS的危险性是CC基因型个体的2.45倍(95%CI=1.78~3.37,P<0.001)。结论 IL-6-572C/G多态GC和GG基因型是AS发生的风险基因型。     

白细胞介素1A基因3'-UTR I/D多态性与中国汉族人群癌症易感性的Meta分析

目的综合分析白细胞介素(IL)1A基因rs3783553单核苷酸多态性与中国汉族人群癌症易感性的关系。方法检索Pubmed、Springer、EMBASE以及中国知网、万方和生物医学文献数据库,检索有关IL-1A基因rs3783553位点多态性与癌症易感性的病例对照研究,利用STATA12.0软件行Meta分析,并进一步行亚组分析、敏感性分析及发表偏倚检测。结果本研究共纳入14篇文献,共计12 369例研究对象,其中癌症患者5 708例,健康对照者6 661例。Meta分析结果显示,等位基因模型I vs.D(OR=0.82,95%CI:0.75~0.89)、纯合子模型II vs.DD(OR=0.62,95%CI:0.55~0.70)、杂合子模型ID vs.DD(OR=0.86,95%CI:0.80~0.93)、隐性基因模型II vs.ID/DD(OR=0.68,95%CI:0.60~0.76)以及显性基因模型II/ID vs.DD(OR=0.81,95%CI:0.75~0.87)中各基因型的癌症易感性差异均存在统计学意义(P均<0.05)。亚组分析结果显示,该基因位点多态性可能与我国汉族人群罹患消化系统恶性肿瘤以及女性罹患生殖系统癌症的风险降低有关。结论 IL-1A基因rs3783553多态性与中国汉族人口癌症易感性相关,其中I等位基因可能是中国汉族人群的保护因素,而等位基因D则可能是其癌症易感因素。     

IL-8-251A/T多态性与肝癌相关性

目的探讨IL-8-251A/T多态性与中国东北地区人群肝癌的相关性。方法应用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)检测243例健康对照个体和229例肝癌患者IL-8-251A/T多态性。结果 IL-8-251A/T多态性在对照组和肝癌组中分布差异不显著(P>0.05)。根据临床分期、分化程度、转移和HBsAg状态进行分层分析,发现HBsAg阴性肝癌患者TT基因型在分布明显高于阳性患者(P=0.002);未发现IL-8-251A/T多态性与临床分期、分化程度和转移状态明显相关(P>0.05)。结论 IL-8-251A/T多态性与肝癌患者HBsAg状态相关。     

白细胞介素8基因多态性与卵巢癌发生的关系

目的研究白细胞介素8(IL-8)+781基因多态性与卵巢癌发生风险之间的关系。方法筛选卵巢癌患者为疖例组和年龄匹配的健康人为对照组,应用聚合酶链反应-限制性片段长度多态性分析检测IL-8+781基因多态性结果携带基因型TT发生卵巢癌的风险显著高于携带基因型CC(OR=3.385,95%CI:1.361~8.418;P=0.009),携带等位基因T发生卵巢癌风险显著高于等位基因C(OR=1.704,95%CI:1.122~2.590;P=0.013)。结论 IL-8+781基因多态性可能影响卵巢癌的发生。     

白细胞介素-8基因-781C/T多态性与肝癌及鼻咽癌发病风险的相关性

目的探讨肿瘤细胞侵袭相关因子白细胞介素(IL)-8遗传多态性和广西壮族人群肝癌与鼻咽癌易感性的关系。方法收集广西壮族肝癌患者260例与鼻咽癌患者251例,同时选取广西壮族健康人群270例为对照。利用单碱基延伸PCR技术和DNA测序法,检测广西壮族肝癌患者、鼻咽癌患者和健康对照者的IL-8基因-781 C/T位点单核苷酸多态性,再用χ~2检验比较基因型和等位基因型分布频率在病例组和对照组之间的差异。结果 IL-8基因位点-781 C/T在肝癌组和对照组之间的基因型和等位基因频率分布无统计学差异(CT/CC:OR=1.14,95%CI=0.79~1.64,χ~2=0.509,P=0.476;TT/CC:OR=0.61,95%CI=0.34~1.10,χ~2=2.775,P=0.096;T/C:OR=0.89,95%CI=0.69~1.15,χ~2=0.778,P=0.363)。同时,IL-8基因位点-781 C/T在鼻咽癌组和对照组之间的基因型和等位基因频率分布也无统计学差异(CT/CC:OR=1.29,95%CI=0.86~1.88,χ~2=1.765,P=0.184;TT/CC:OR=1.34,95%CI=0.79~2.27,χ~2=1.172,P=0.279;T/C:OR=1.18,95%CI=0.92~1.52,χ~2=1.749,P=0.186)。结论在广西壮族人群中,IL-8基因-781 C/T位点的遗传多态性可能和肝癌与鼻咽癌的易感性无关。     

中国人群白细胞介素-1α基因多态性与阿尔茨海默病易感性的关系

目的探索中国人群白细胞介素(IL)-1α基因第889位C→T突变(C889T)多态性与阿尔茨海默病(AD)的关系。方法采用固定效应模型或随机效应模型对符合条件的研究进行Meta分析。结果 AD患者1 915例,对照1 726例。基因模型T vs C、TT vs CC、TT+CT vs CC、TT vs CT+CC的OR值分别为1.13,1.95,1.11,1.85,95%CI=0.88¹.44,1.111.44,1.11¹3.43,0.8513.43,0.85¹.45,1.051.45,1.05³.25。结论 IL-1αC889T多态性与AD的易感性相关。     

High polymorphism in the trisomic portion of a gastric cancer cell line

Background Genetic instability is a hallmark of malignancy, and microsatellite instability is a widely appreciated mechanism of generating genetic changes. We have recently observed four markers clustered on chromosome 20 that showed the effects of microsatellite instability in the gastric adenocarcinoma cell line SNU-1. Each affected marker had alleles of three different sizes. The aim of this study was to investigate the origin for this high-density polymorphism on a single chromosome. Methods The high polymorphism located on chromosome 20 was confirmed using 37 additional markers. To further evaluate this finding, 15 clones of the cell line were generated and then assayed with the triallelic markers. Results All told, almost a third of the markers on chromosome 20 had triallelic patterns, but only 0.3% of the markers not on chromosome 20 showed this result. The number of clones showing allelic variation was an average of 50% greater for chromosome 20 markers than for markers elsewhere. A karyotype analysis showed that the progenitor cell line of SNU-1 was trisomic for chromosome 20, and the high polymorphism on that chromosome is almost certainly due to the trisomy. Conclusions Not only are there more chromosome copies and therefore more gene copies subject to mutation in cells containing trisomy, but also more mutations may be passed on to the progeny. This elevated polymorphism increases the repertoire of genetic changes that could affect cellular growth, and may independently increase genomic instability.     

Interleukin-8 gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability

BACKGROUND AND AIM: Gastric carcinoma (GC) with microsatellite instability (MSI) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) GC. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of MSI remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia GC. The objective of this study was to elucidate the relationship between cytokine polymorphisms and MSI phenotypes. METHODS: In a case-control study including 482 controls and 181 patients with GC, interleukin (IL)-8 -251, IL-1B-511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of MSI and mutations in exons 5 to 8 of the p53 gene were examined in GC cases. All clinicopathological data were collected from individual records. RESULTS: High and low frequency of MSI (MSI-H and MSI-L) and MSS were detected in 16 (8.8%), 14 (7.7%) and 151 (83.4%) GC cases, respectively. We found that IL-8 -251 T/T genotype was significantly associated with increased risk of MSI-H GC compared to MSI-L/MSS GC and controls. We found no association between other cytokine polymorphisms and MSI-H GC. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than MSI-L/MSS GC. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. CONCLUSIONS: Our study shows that MSI-H GC is associated with IL-8-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking.     

CXCL12 rs1801157基因多态性与乳腺癌易感性关联的Meta分析

目的探讨CXCL12 rs1801157基因多态性与乳腺癌易感性的关系。方法通过计算机检索和手工检索,收集有关CXCL12 rs1801157基因多态性与乳腺癌易感性关系的文献,筛选出符合条件的文献,应用M eta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%可信区间,并行敏感性分析和发表偏倚的评估。结果共5篇符合条件文献纳入本研究,病例组1 058例,对照组1023例。Meta分析合并结果显示CXCL12 rs1801157基因A等位基因携带者乳腺癌发生率明显高于G等位基因携带者（OR=1.32,95%CI=1.15~1.51,P〈0.01）;AA∶GG,GA∶GG和AA＋GA∶GG合并OR值及其95%可信区间分别是1.64（95%CI=1.16~2.33）、1.42（95%CI=1.18~1.70）和1.44（95%CI=1.21~1.72）。敏感性分析表明合并结果不受单个研究的影响,未发现发表偏倚,结论可靠。结论 CXCL12 rs1801157基因多态性可能与乳腺癌易感性有关,A等位基因可能增加乳腺癌的发病。     

Multi-drug resistance 1 polymorphism is associated with reduced risk of gastric cancer in the Japanese population

BACKGROUND AND AIMS: Host genetic factors play a key role in gastric carcinogenesis, but the mechanism has not been clarified. The multi-drug resistance 1 (MDR1) gene mediates the expression of P-glycoprotein, which has a role in active transport of various substrates, including xenobiotics, and thus has a protective function in various tissues and organs like gastrointestinal epithelial cells. C3435T polymorphism in exon 26 of the MDR1 gene influences P-glycoprotein expression and activity in the gastrointestinal tract. We investigated the influences of MDR1 gene polymorphism on the risk of gastric cancer. METHOD: The study was performed on 157 patients with gastric cancer (GC) and 104 patients without GC as the control group. C3435T polymorphism of MDR1 was investigated by PCR-RFLP in all of the patients. RESULTS: The MDR1 3435 TT genotype showed a significantly higher frequency in controls than in GC patients (OR = 0.43; 95% CI = 0.23-0.79). There were no significant differences of the CT and CC genotype frequencies between GC patients and controls. We also found that the 3435TT genotype of MDR1 was associated with a lower risk of non-cardiac cancer (OR = 0.42; 95% CI = 0.23-0.79), middle-third cancer (OR = 0.36; 95% CI = 0.17-0.77), advanced cancer (OR = 0.31; 95% CI = 0.13-0.73), venous invasion (OR = 0.30; 95% CI = 0.10-0.91), and lymph node metastasis (OR = 0.28; 95% CI = 0.13-0.65). CONCLUSION: Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population.     

Association between polymorphism rs6983267 and gastric cancer risk in Chinese population

AIM: To explore the association between single nucleotide polymorphisms (SNPs) at 8q24 and gastric cancer risk. METHODS: A case-control investigation including 212 gastric cancer patients and 377 healthy controls was conducted. The genotypes of SNPs (rs6983267, rs7008482 and rs10808555) were examined and established through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to evaluate the association between SNPs and gastric canc...     

XRCC1 genetic polymorphism Arg399GIn and gastric cancer risk： A meta-analysis

AIM： To evaluate the association between X-ray crosscomplementing gene 1 （XRCCl） genetic polymorphism Arg399Gln and gastric cancer risk by means of metaanalysis. METHODS： We searched PubMed and NCBI up to June 1, 2008. A total of 16 clinical trials and reports were identified, but only 8 trials qualified under our selection criteria. Statistical analysis was performed with the software program Review Manage, version 4.2.8. RESULTS： Of the 8 case-control studies selected for this meta-analysis, a total of 1334 gastric cancer cases and 2194 controls were included. For Arg399GIn, the Gin/Gin genotype carriers did not have a decreased cancer risk compared with those individuals with the Arg/Arg genotype （OR = 0.92, 95% CI, 0.71-1.19; P = 0.51）. Similarly, no associations were found in the recessive and dominant modeling （Gin/Gin vs Arg/GIn ＋ Arg/Arg： OR = 0.96; 95% CI, 0.77-1.19; P = 0.70 and Gin/Gin ＋ Arg/GIn vs Arg/Arg： OR = 0.90, 95% CI, 0.77-1.05; P = 0.18）. CONCLUSION： No association is found between the XRCC1 polymorphism Arg399GIn and gastric cancer risk.     

Card15 mutations and gastric cancer in a Portuguese population

Abstract

Background. CARD15 is involved in the innate immune response and mutations of this gene have been linked with increased risk of Crohn's disease and colorectal cancer. The relation between CARD15 mutations and gastric cancer (GC) remains controversial. Aims. To assess whether CARD15 mutations are risk factors for GC in Portugal and whether there are genotype–phenotype correlations in these patients. Methods. The 3 main CARD15 mutations (3020insC, R702W and G908R) were searched in 150 patients with GC and in 202 healthy controls. Results. Overall, CARD15 mutations were found in 28 patients (18.7%) and in 27 controls (13.4%) (p = 0.176). Individually, the incidence of 3020insC was significantly higher in patients than in controls (6.0% vs. 1.0%, p = 0.021). This polymorphism was linked with an increased risk for the intestinal-type of GC (p = 0.002), while no association was found with the diffuse and/or mixed types. Genotype frequencies for R702W (10.0% vs. 7.9%) and G908R (4.0% vs. 4.0%) were not statistically different between the two groups. Similarly, no significant associations were detected between these two polymorphisms and the different histological GC types. No correlations were observed between CARD15 mutations and family history, mean age at diagnosis or GC stage. Conclusions. The CARD15 3020insC variant is a risk factor for intestinal GC in Portugal. CARD15 variants are not correlated with age of diagnosis or family aggregation of the disease neither with the GC stage.     

Association between interleukin-1 gene polymorphisms and Helicobacter pylori infection in gastric carcinogenesis in a Chinese population

BACKGROUND AND AIM: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin-1 (IL-1) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine polymorphisms of IL-1B and IL-1 receptor antagonist (IL-1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients. METHODS: Three hundred and ninety-nine patients with gastroduodenal diseases (129 chronic gastritis, 127 duodenal ulcer and 143 non-cardiac gastric cancer) and 264 healthy controls were genotyped for IL-1B-511 and IL-1RN gene polymorphisms by the PCR-RFLP method. H. pylori infection status was determined by a validated serological test. RESULTS: The frequency of IL-1B-511 T allele was significantly higher in H. pylori positive patients with non-cardiac gastric cancer than in both H. pylori negative patients with non-cardiac gastric cancer (60%vs 46%, P = 0.0342, OR = 1.666, 95% confidence interval [CI]: 1.045-2.656) and in healthy controls (60%vs 48%, P = 0.0071, OR = 1.665, 95%CI: 1.149-2.412). However, the polymorphism was not associated with chronic gastritis and duodenal ulcer. Multivariate logistic regression analyses identified that IL-1B-511 T/T carrier status was an independent risk factor for non-cardiac gastric cancer in the presence of H. pylori infection (adjusted OR = 3.01, 95%CI: 1.27-7.11, P = 0.01), and the frequency of IL-1B-511 T allele was an increased risk factor for developing gastric cancer (P = 0.03, adjusted OR = 2.29, 95%CI: 1.08-4.86). There was no association between IL-1RN gene polymorphisms and H. pylori infection and other gastroduodenal diseases. CONCLUSION: IL-1B-511 T allele is associated with H. pylori infection in non-cardiac gastric cancer in a Chinese population. The IL-1B-511 gene polymorphism appears to play an important role in gastric carcinogenesis in Chinese patients with H. pylori infection.     

p53 codon 72 polymorphism and liver cancer susceptibility: a meta-analysis of epidemiologic studies

AIM:To evaluate the association between p53 codon 72 polymorphism and liver cancer risk by means of meta-analysis. METHODS:Two investigators independently searched the Medline,Embase and Chinese Biomedicine databases.Summary odds ratios and 95%CI for p53 codon 72 polymorphism and liver cancer were calculated in fixedeffects model(Mantel-Haenszel method)and randomeffects model(DerSimonian and Laird method)when appropriate. RESULTS:This meta-analysis included 1115 liver cancer cases and 1778 controls.The comb...