PSCA rs2294008基因多态性与胃癌癌前病变的相关性研究

发布时间：2018-04-10 13:14

本文选题：前列腺干细胞抗原 + 胃肿瘤　；参考：《大连医科大学》2017年硕士论文

【摘要】：研究背景在影响消化道的肿瘤中胃癌占据了很有意义的比例。在胃癌的早期发现过程中,属于胃癌的特异性生物标志物相对缺乏,以至于不能很好地实现胃癌的早期预警和早期诊断,这是目前不能对胃癌进行早期干预的重要原因,目前大部分胃癌确诊时已经是晚期,带来了很大的社会负担。因此,根究出相应的生物标记信号对胃癌的提早预警诊断相对有价值。胃癌在不同的地域、年龄、性别、血型、饮食习惯中表现出高度的异型性和不同的病理类型,胃癌的发病原因并不是很确切,目前幽门螺杆菌(Hp)感染、环境成分和宿主遗传因素在胃癌发病的病因学中已经被确定出来,其中胃癌形成期间的遗传因素包括个体遗传具有举足轻重的地位。单核苷酸多态性(SNPs)目前作为遗传因素的代表被大范围地用来探讨胃癌的发病危害和预期价值。前列腺干细胞抗原基因(prostate stem cell antigen,PSCA)位点多态性与胃癌、前列腺癌和十二指肠溃疡等疾病的发病风险存在一定的关系。从PSCA通过全基因关联组被筛选出来后,它作为胃癌相关的候选基因受到了广泛地关注,关于该基因多态性(rs2294008,rs2976392)和胃癌的相关性在不同的人群和地区进行了研究,然而研究却取得了不一致的结果。目前大多数研究是对rs2294008和rs2976392进行单中心位点分析,既往研究显示前列腺干细胞抗原(PSCA)基因rs2294008位点多态性与胃部疾病的发生有一定的关联。考虑到不一样的研究中发现各自群体中PSCA基因的SNPs,其频率的分散趋势也存在差异,并且各异的频率分布在不一样的疾病中也有出入,目前山东地区关于PSCA基因多态性对于胃癌癌前病变的研究相对较少,以青岛区为研究对象对探索PSCA基因的功能和胃癌的发病机制具有重要意义。研究目的探讨PSCArs2294008位点基因多态性与长久居住生活在山东省青岛市汉族人群的胃癌癌前病变(肠上皮化生、上皮内瘤变)的关系,为胃癌提早预测供给有效地检测手段。研究方法本次研究收纳从2009年11月至2015年11月时间段内在青岛市市立医院住院或就诊的398例患者,取得患者同意,其中包含肠上皮化生328例,上皮内瘤变70例。同—时间段选取本院416例健康体检者的胃粘膜作为对照组,也同时取得患者同意。PSCArs2294008位点的基因型分布情况是应用PCR直接测序的方法来进行测评的,与此同时Hp的感染状况本实验是应用快速尿素酶试验来进行的,实验所得的数据应用SPSS17.0进行统计学分析。研究结果检测出实验组和对照组中PSCA rs2294008基因位点有三种分别为CC、CT和TT基因型,病例组中三种基因型的分布与对照组相比是存在区别的,具有统计学的意义(P=0.011),实验组TT基因型位点的分布频率和对照组的TT基因型频率相比较是明显增高的(16.3%对9.4%,P=0.003)。和CC基因型携带者来比较,TT基因型携带者的胃癌癌前病变的发病风险有所增加,其中(OR=1.840,95%CI:1.174～2.886)。和Hp感染为阴性同时为CC+CT基因型者作比较,单一携带TT基因型稍微(OR=1.783,95%CI:0.9004～3.530)增加胃癌癌前病变的发病风险,然而单一的Hp感染却会让发病的风险增加(OR=2.389,95%CI:1.799～3.173),同时具有Hp感染和携带TT基因型(OR=3.335,95%CI:1.935～5.749)可以使胃癌癌前病变的发病风险显著增加,两种因素联合的作用相对比较明显。研究结论在青岛地区的常住汉族人群中PSCArs2294008位点基因多态性在病例组和健康对照组中分布差异具有统计学意义,同时和胃粘膜相关性疾病肠上皮化生、上皮内瘤变的易感性存在一定的关联,Hp感染可以让PSCA rs2294008 TT基因型携带者发生肠上皮化生、上皮内瘤变的危险性进一步增加。
[Abstract]:Research background in the digestive tract tumor effect in gastric cancer occupies a very significant proportion. In the early discovery process, which belongs to the gastric cancer specific biomarkers of the relative lack of, that can not achieve a good early warning and early diagnosis of gastric cancer, which is an important reason to early intervention on gastric cancer at present at present, the majority of cancer are diagnosed in the late stage, brings great burden on society. Therefore, according to the corresponding signal of biological markers for gastric cancer early diagnosis and early warning of relative value of gastric cancer. In different regions, age, gender, blood type, exhibit a high degree of atypia and different pathological types of diet in gastric cancer the cause is not very precise, the Helicobacter pylori (Hp) infection, environmental components and host genetic factors in the etiology of gastric cancer have been identified, including the formation of gastric cancer Genetic factors include individual genetic period has a pivotal position. The single nucleotide polymorphism (SNPs) at present as a representative of the genetic factors are widely used to explore the incidence of gastric cancer risk and the expected value. Prostate stem cell antigen gene (prostate stem cell antigen, PSCA) polymorphism and gastric cancer, there is a certain relationship between the risk of prostate cancer and duodenal ulcer disease. From PSCA through genome-wide association group were screened out after it as candidate genes related to gastric cancer has been widely concerned about the gene polymorphisms (rs2294008, rs2976392) and gastric cancer correlation were studied in different populations and regions, but it has been inconsistent results. Most of the research is the analysis of a single center site on rs2294008 and rs2976392, previous studies have shown that prostate stem cell antigen (PSCA) base Due to the occurrence of rs2294008 polymorphism and gastric diseases have certain relevance. Considering the respective PSCA group gene SNPs study found that not the same, there are differences in the frequency dispersion trend, and different frequency distribution in different diseases also differ, at present Shandong area about PSCA gene polymorphism for study on precancerous lesions of gastric cancer is relatively small, taking Qingdao area as the research object has an important significance to explore the function of PSCA gene and the pathogenesis of gastric cancer. Objective to investigate the PSCArs2294008 gene polymorphism and long living in gastric precancerous lesions in Han population of Shandong province in Qingdao city (intestinal metaplasia, intraepithelial neoplasia variable) relationship, gastric cancer early detection methods. Supply forecast effectively the research methods included from November 2009 to November 2015 time period in Qingdao Municipal Hospital 398 cases of hospital or clinic patients were agreed, including 328 cases of intestinal metaplasia, 70 cases of intraepithelial neoplasia. Select the same period 416 cases of healthy gastric mucosa as control group, also made the patients agreed to genotype.PSCArs2294008 locus distribution method using PCR direct sequencing to evaluate the Hp infection status at the same time, this study is the application of rapid urease test for the application of SPSS17.0 data, the experimental results were analyzed statistically. The results detected in the experimental group and the control group in PSCA locus of rs2294008 three were CC, CT and TT genotypes are different compared with the three genotypes in the case group distribution and control group, with statistical significance (P=0.011), TT genotype frequency distribution and the control group and the experimental group TT genotype is significantly increased compared to the High (16.3% vs. 9.4%, P=0.003). And the CC genotype compared to TT genotype carriers, the risk of precancerous lesions of gastric cancer has increased, among them (OR=1.840,95%CI:1.174 ~ 2.886). Compare and negative for Hp infection and CC+CT genotype, TT genotype (a single OR=1.783,95%CI:0.9004 ~ 3.530) increase the risk of precancerous lesions of gastric cancer, however, it will make the incidence of Hp infection increased risk (OR=2.389,95%CI:1.799 ~ 3.173), at the same time with Hp infection and TT genotype (OR=3.335,95%CI:1.935 ~ 5.749) can make the risk of precancerous lesions of gastric cancer increased significantly, two factors combined with the relatively obvious. The gene polymorphism of PSCArs2294008 locus in the conclusion of the study in the Qingdao area resident in Han population in the patient group and healthy control group with a significant difference in the distribution, at the same time and gastric mucosa There is a certain correlation between the related diseases, intestinal metaplasia and susceptibility to intraepithelial neoplasia. Hp infection can cause intestinal metaplasia in PSCA rs2294008 TT genotype carriers, and the risk of intraepithelial neoplasia is further increased.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

【参考文献】