幽门螺杆菌的诊断及相关基因多态性与胃癌易感性的关联研究
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摘要
背景:寻找操作简便的准确的非侵入性检测方法对于幽门螺杆菌(H.pylori)现症感染的诊断非常重要。
目的:评估应用胶体金免疫层析技术的商用血清学试剂盒Assure(?)幽门螺杆菌快速检测(Genelabs Diagnostics Pte Ltd,SingaporeCIM test)试验在幽门螺杆菌根除治疗前后的应用价值。
方法:452名来自江苏省的志愿者纳入本研究,每位志愿者均接受~(13)C-尿素呼气试验(~(13)C-UBT)。其中115例是经~(13)C-尿素呼气试验确诊为幽门螺杆菌阳性的门诊病人,用来评估血清学试剂盒在根治治疗后的应用价值,该115门诊病人接受一周三联疗法(质子泵如奥美拉唑、兰索拉唑或雷贝拉唑加两种抗生素如克拉霉素、阿莫西林或甲硝唑),根治治疗一个月后患者复查~(13)C-尿素呼气试验,同时在1、3、6个月分别采集血标本,以血清学试剂盒行免疫层析。以~(13)C-尿素呼气试验为金标准,评估该检测方法在根治前后的敏感性、特异性、阳性预测值、阴性预测值、准确性。
结果:根据诊断金标准,337例未接受根除治疗志愿者的H.pylori感染率为65.6%(221/337),血清学试剂盒诊断的敏感性、特异性、阳性预测值、阴性预测值和准确性分别为93.2%,90.5%,94.9%,87.5%和92.3%。接受根除治疗的115例患者未有失访,94例患者成功根除H.pylori,根除率81.7%。根治治疗一个月后CIM test检测的敏感性特异性分别为50.0%、66.7%,三个月后为66.7%、84.6%,根治治疗六个月后其敏感性特异性提高到85.7%、96.9%。
结论:CIM test是一种简单、快速、可靠的非侵入性H.pylori感染诊断方法,在未行根除治疗的患者中有很好的应用前景,但是在根除治疗六个月内它不能区分现症感染还是过去感染。
背景目的:胃癌(Gastric cancer)是常见的恶性肿瘤之一,幽门螺杆菌(H.pylori)感染是慢性胃炎、消化性溃疡的主要病因已经得到医学界认可,其与胃癌的关系也引起人们的广泛关注。然而,胃癌的发病机制并不明确,一般认为是一个多因素(H.pylori感染、宿主因素、环境因素)、多阶段的过程。本课题通过对鼠双微体(mouse double minute mdm2)基因启动子区域309位点基因多态性的研究,描述其等位基因在江苏汉族人群中的分布,从宿主方面探讨宿主基因多态性在致胃癌中的作用,阐明我国江苏人群MDM2基因多态性与胃癌的关系。
方法:本研究采用病例—对照研究的方法;病例组为病理确诊的胃癌患者(260例),对照组为南京市和高邮市的无肿瘤患病史的社区人群或健康体检者,按年龄与病例进行频数匹配,共260例,收集两组病人的临床资料,包括年龄、性别、胃癌家族史、烟、酒消费情况、病理结果等;所有研究对象均为江苏省汉族人,采用PCR-RFLP(PCR-Restriction FragmentLength Polymorphism)法进行基因分型,应用Assure(?)Hp抗体测定层析板(新加坡Genelabs公司产品)检测血清Hp抗体。
结果:病例组对照组间年龄性别均衡可比,本地区Hp感染率为66.9%,病例组的Hp感染率为72.3%,差异未见有明显统计学意义。对照组基因频率分布符合Hardy-Weinberg遗传平衡定律,具有良好的代表性,MDM2 SNP309三种基因型(野生型TT、杂合型TG、变异型纯合GG)在胃癌组的分布频率分别为28.5%、46.2%、25.4%,在对照组的分布频率分别为31.5%、54.2%、14.2%,MDM2 SNP 309G/G基因型明显增加患胃癌的风险,与TT基因型相比OR值为1.977(95%CI=1.186-3.294),经多因素(年龄、性别、Hp)调整后OR值为1.980(95%CI=1.186-3.307),与TT+TG基因型相比,经多因素调整后OR值为2.048(95%CI=1.310-3.203)。MDM2GG基因型与幽门螺杆菌感染之间有相互作用导致胃癌的发病风险增加了约3倍。
结论:本次研究发现MDM2基因启动子区SNP 309与胃癌易感性相关联,并且该多态性与幽门螺杆菌感染之间有相互作用,可显著增加胃癌的发病风险。
Background & Aims:Development of an accurate and noninvasive method to detect current Helicobacter pylori infection is essential in clinic.The aim was to evaluate the performance of the CIM test for current H.pylori infection before and after eradication therapy in Chinese.
Methods:452 eligible people were recruited.Each individual underwent a ~(13)C-UBT.115 H.pylori-positive outpatients were treated with one-week triple therapy for the evaluation of CIM test performed 1, 3 and 6 months after eradication.Its performance(sensitivity, specificity,etc.)was determined using the ~(13)C-UBT as a gold standard.
Results:H.pylori was detected in 221(65.6%)of the 337 people by ~(13)C-UBT.The sensitivity,specificity,positive and negative predictive values and accuracy of the CIM test were 93.2%,90.5%, 94.9%,87.5%,and 92.3%,respectively.The sensitivity and specificity of CIM test were 50.0%and 66.7%one month after eradication therapy,and they increased to 85.7%and 96.9%six months after the therapy.
Conclusions:The CIM test is a simple,rapid,accurate,cheap and near-people test.It may be satisfactory for detecting H.pylori infection in cases without eradication therapy,but it could not differentiate the past or current infection within 6 months after anti-H,pylori therapy.
Background & Aims:
Gastric cancer is the common cancer in the world and particularly prevalent in certain countries including China.H pylori is a definite careinogen for gastric adenocarcinoma.However,the underlying pathogenic mechanisms have not been fully understood,although the interactions between environmental,bacterial and multiple genetic components are likely to be involved.MDM2(mouse double minute)is an oncogene,and can inhibit p53 passway.We hypothesized that genetic variations of MDM2(SNP309)was associated with gastric cancer susceptibility.To test this hypothesis, we performed genotyping analysis for MDM2 309T＞G in a casecontrol study of 260 gastric cancer cases and 260 age and sex frequency-matched healthy controls from Han population of Jiangsu province.
Methods:
This study consisted of 260 patients with gastric cancer and 260 healthy controls.All subjects were unrelated ethnic Han Chinese and residents in Jiangsu Province.All cases were pathologically diagnosed as gastric carcinoma.The population controls were selected from cancer-free individuals living in Jiangsu Province,and were frequency matched to the cases on age(±5 years)and sex.Trained interviewers used a pre-tested questionnaire to determine demographic and lifestyle characteristics,such as sex,age,and related risk factors,including tobacco smoking,alcohol drinking,etc. SNP309 was genotyped by polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP).The indirect solid phase immunochromatographic assay was used to investigate the presence of IgG antibodies to H.pylori(Genelabs Diagnostics Pty Ltd, Singapore).
Results:
The cancer cases and controls seemed to be adequately matched in terms of sex and age.There was no difference between patients and controls in Hp seropositivity.The observed genotype frequencies of MDM2 polymorphism was in Hardy-Weinberg equilibrium in the controls(P=0.06).Distributions of MDM2 genotypes were then compared among patients and controls.The frequencies of MDM2 TT, TG,and GG genotypes among patients were significantly different from those among controls(P=0.006),with the GG homozygotes being overrepresented among patients compared with controls(25.4% versus 14.2%;P=0.009).The MDM2 GG genotype was associated with an increased risk of developing GC(OR,1.98;95%CI, 1.186-3.307;P=0.009),compared with TT genotype.However,the heterozygous genotypes MDM2 TG was not associated with the risk. Significant interactions were observed between polymorphisms and Hp,with risk being the highest(OR,2.947;95%CI,1.592-5.457)in Hp seropositivity having MDM2 GG genotypes.
Conclusions:
In conclusion,our study shows a significant association between functional polymorphisms in MDM2 and increased risk of gastric cancer
目的:评估应用胶体金免疫层析技术的商用血清学试剂盒Assure(?)幽门螺杆菌快速检测(Genelabs Diagnostics Pte Ltd,SingaporeCIM test)试验在幽门螺杆菌根除治疗前后的应用价值。
方法:452名来自江苏省的志愿者纳入本研究,每位志愿者均接受~(13)C-尿素呼气试验(~(13)C-UBT)。其中115例是经~(13)C-尿素呼气试验确诊为幽门螺杆菌阳性的门诊病人,用来评估血清学试剂盒在根治治疗后的应用价值,该115门诊病人接受一周三联疗法(质子泵如奥美拉唑、兰索拉唑或雷贝拉唑加两种抗生素如克拉霉素、阿莫西林或甲硝唑),根治治疗一个月后患者复查~(13)C-尿素呼气试验,同时在1、3、6个月分别采集血标本,以血清学试剂盒行免疫层析。以~(13)C-尿素呼气试验为金标准,评估该检测方法在根治前后的敏感性、特异性、阳性预测值、阴性预测值、准确性。
结果:根据诊断金标准,337例未接受根除治疗志愿者的H.pylori感染率为65.6%(221/337),血清学试剂盒诊断的敏感性、特异性、阳性预测值、阴性预测值和准确性分别为93.2%,90.5%,94.9%,87.5%和92.3%。接受根除治疗的115例患者未有失访,94例患者成功根除H.pylori,根除率81.7%。根治治疗一个月后CIM test检测的敏感性特异性分别为50.0%、66.7%,三个月后为66.7%、84.6%,根治治疗六个月后其敏感性特异性提高到85.7%、96.9%。
结论:CIM test是一种简单、快速、可靠的非侵入性H.pylori感染诊断方法,在未行根除治疗的患者中有很好的应用前景,但是在根除治疗六个月内它不能区分现症感染还是过去感染。
背景目的:胃癌(Gastric cancer)是常见的恶性肿瘤之一,幽门螺杆菌(H.pylori)感染是慢性胃炎、消化性溃疡的主要病因已经得到医学界认可,其与胃癌的关系也引起人们的广泛关注。然而,胃癌的发病机制并不明确,一般认为是一个多因素(H.pylori感染、宿主因素、环境因素)、多阶段的过程。本课题通过对鼠双微体(mouse double minute mdm2)基因启动子区域309位点基因多态性的研究,描述其等位基因在江苏汉族人群中的分布,从宿主方面探讨宿主基因多态性在致胃癌中的作用,阐明我国江苏人群MDM2基因多态性与胃癌的关系。
方法:本研究采用病例—对照研究的方法;病例组为病理确诊的胃癌患者(260例),对照组为南京市和高邮市的无肿瘤患病史的社区人群或健康体检者,按年龄与病例进行频数匹配,共260例,收集两组病人的临床资料,包括年龄、性别、胃癌家族史、烟、酒消费情况、病理结果等;所有研究对象均为江苏省汉族人,采用PCR-RFLP(PCR-Restriction FragmentLength Polymorphism)法进行基因分型,应用Assure(?)Hp抗体测定层析板(新加坡Genelabs公司产品)检测血清Hp抗体。
结果:病例组对照组间年龄性别均衡可比,本地区Hp感染率为66.9%,病例组的Hp感染率为72.3%,差异未见有明显统计学意义。对照组基因频率分布符合Hardy-Weinberg遗传平衡定律,具有良好的代表性,MDM2 SNP309三种基因型(野生型TT、杂合型TG、变异型纯合GG)在胃癌组的分布频率分别为28.5%、46.2%、25.4%,在对照组的分布频率分别为31.5%、54.2%、14.2%,MDM2 SNP 309G/G基因型明显增加患胃癌的风险,与TT基因型相比OR值为1.977(95%CI=1.186-3.294),经多因素(年龄、性别、Hp)调整后OR值为1.980(95%CI=1.186-3.307),与TT+TG基因型相比,经多因素调整后OR值为2.048(95%CI=1.310-3.203)。MDM2GG基因型与幽门螺杆菌感染之间有相互作用导致胃癌的发病风险增加了约3倍。
结论:本次研究发现MDM2基因启动子区SNP 309与胃癌易感性相关联,并且该多态性与幽门螺杆菌感染之间有相互作用,可显著增加胃癌的发病风险。
Background & Aims:Development of an accurate and noninvasive method to detect current Helicobacter pylori infection is essential in clinic.The aim was to evaluate the performance of the CIM test for current H.pylori infection before and after eradication therapy in Chinese.
Methods:452 eligible people were recruited.Each individual underwent a ~(13)C-UBT.115 H.pylori-positive outpatients were treated with one-week triple therapy for the evaluation of CIM test performed 1, 3 and 6 months after eradication.Its performance(sensitivity, specificity,etc.)was determined using the ~(13)C-UBT as a gold standard.
Results:H.pylori was detected in 221(65.6%)of the 337 people by ~(13)C-UBT.The sensitivity,specificity,positive and negative predictive values and accuracy of the CIM test were 93.2%,90.5%, 94.9%,87.5%,and 92.3%,respectively.The sensitivity and specificity of CIM test were 50.0%and 66.7%one month after eradication therapy,and they increased to 85.7%and 96.9%six months after the therapy.
Conclusions:The CIM test is a simple,rapid,accurate,cheap and near-people test.It may be satisfactory for detecting H.pylori infection in cases without eradication therapy,but it could not differentiate the past or current infection within 6 months after anti-H,pylori therapy.
Background & Aims:
Gastric cancer is the common cancer in the world and particularly prevalent in certain countries including China.H pylori is a definite careinogen for gastric adenocarcinoma.However,the underlying pathogenic mechanisms have not been fully understood,although the interactions between environmental,bacterial and multiple genetic components are likely to be involved.MDM2(mouse double minute)is an oncogene,and can inhibit p53 passway.We hypothesized that genetic variations of MDM2(SNP309)was associated with gastric cancer susceptibility.To test this hypothesis, we performed genotyping analysis for MDM2 309T＞G in a casecontrol study of 260 gastric cancer cases and 260 age and sex frequency-matched healthy controls from Han population of Jiangsu province.
Methods:
This study consisted of 260 patients with gastric cancer and 260 healthy controls.All subjects were unrelated ethnic Han Chinese and residents in Jiangsu Province.All cases were pathologically diagnosed as gastric carcinoma.The population controls were selected from cancer-free individuals living in Jiangsu Province,and were frequency matched to the cases on age(±5 years)and sex.Trained interviewers used a pre-tested questionnaire to determine demographic and lifestyle characteristics,such as sex,age,and related risk factors,including tobacco smoking,alcohol drinking,etc. SNP309 was genotyped by polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP).The indirect solid phase immunochromatographic assay was used to investigate the presence of IgG antibodies to H.pylori(Genelabs Diagnostics Pty Ltd, Singapore).
Results:
The cancer cases and controls seemed to be adequately matched in terms of sex and age.There was no difference between patients and controls in Hp seropositivity.The observed genotype frequencies of MDM2 polymorphism was in Hardy-Weinberg equilibrium in the controls(P=0.06).Distributions of MDM2 genotypes were then compared among patients and controls.The frequencies of MDM2 TT, TG,and GG genotypes among patients were significantly different from those among controls(P=0.006),with the GG homozygotes being overrepresented among patients compared with controls(25.4% versus 14.2%;P=0.009).The MDM2 GG genotype was associated with an increased risk of developing GC(OR,1.98;95%CI, 1.186-3.307;P=0.009),compared with TT genotype.However,the heterozygous genotypes MDM2 TG was not associated with the risk. Significant interactions were observed between polymorphisms and Hp,with risk being the highest(OR,2.947;95%CI,1.592-5.457)in Hp seropositivity having MDM2 GG genotypes.
Conclusions:
In conclusion,our study shows a significant association between functional polymorphisms in MDM2 and increased risk of gastric cancer
引文
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