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PSCA rs2294008基因多態(tài)性與胃癌癌前病變的相關性研究

發(fā)布時間:2018-04-10 13:14

  本文選題:前列腺干細胞抗原 + 胃腫瘤; 參考:《大連醫(yī)科大學》2017年碩士論文


【摘要】:研究背景在影響消化道的腫瘤中胃癌占據了很有意義的比例。在胃癌的早期發(fā)現過程中,屬于胃癌的特異性生物標志物相對缺乏,以至于不能很好地實現胃癌的早期預警和早期診斷,這是目前不能對胃癌進行早期干預的重要原因,目前大部分胃癌確診時已經是晚期,帶來了很大的社會負擔。因此,根究出相應的生物標記信號對胃癌的提早預警診斷相對有價值。胃癌在不同的地域、年齡、性別、血型、飲食習慣中表現出高度的異型性和不同的病理類型,胃癌的發(fā)病原因并不是很確切,目前幽門螺桿菌(Hp)感染、環(huán)境成分和宿主遺傳因素在胃癌發(fā)病的病因學中已經被確定出來,其中胃癌形成期間的遺傳因素包括個體遺傳具有舉足輕重的地位。單核苷酸多態(tài)性(SNPs)目前作為遺傳因素的代表被大范圍地用來探討胃癌的發(fā)病危害和預期價值。前列腺干細胞抗原基因(prostate stem cell antigen,PSCA)位點多態(tài)性與胃癌、前列腺癌和十二指腸潰瘍等疾病的發(fā)病風險存在一定的關系。從PSCA通過全基因關聯組被篩選出來后,它作為胃癌相關的候選基因受到了廣泛地關注,關于該基因多態(tài)性(rs2294008,rs2976392)和胃癌的相關性在不同的人群和地區(qū)進行了研究,然而研究卻取得了不一致的結果。目前大多數研究是對rs2294008和rs2976392進行單中心位點分析,既往研究顯示前列腺干細胞抗原(PSCA)基因rs2294008位點多態(tài)性與胃部疾病的發(fā)生有一定的關聯?紤]到不一樣的研究中發(fā)現各自群體中PSCA基因的SNPs,其頻率的分散趨勢也存在差異,并且各異的頻率分布在不一樣的疾病中也有出入,目前山東地區(qū)關于PSCA基因多態(tài)性對于胃癌癌前病變的研究相對較少,以青島區(qū)為研究對象對探索PSCA基因的功能和胃癌的發(fā)病機制具有重要意義。研究目的探討PSCArs2294008位點基因多態(tài)性與長久居住生活在山東省青島市漢族人群的胃癌癌前病變(腸上皮化生、上皮內瘤變)的關系,為胃癌提早預測供給有效地檢測手段。研究方法本次研究收納從2009年11月至2015年11月時間段內在青島市市立醫(yī)院住院或就診的398例患者,取得患者同意,其中包含腸上皮化生328例,上皮內瘤變70例。同—時間段選取本院416例健康體檢者的胃粘膜作為對照組,也同時取得患者同意。PSCArs2294008位點的基因型分布情況是應用PCR直接測序的方法來進行測評的,與此同時Hp的感染狀況本實驗是應用快速尿素酶試驗來進行的,實驗所得的數據應用SPSS17.0進行統(tǒng)計學分析。研究結果檢測出實驗組和對照組中PSCA rs2294008基因位點有三種分別為CC、CT和TT基因型,病例組中三種基因型的分布與對照組相比是存在區(qū)別的,具有統(tǒng)計學的意義(P=0.011),實驗組TT基因型位點的分布頻率和對照組的TT基因型頻率相比較是明顯增高的(16.3%對9.4%,P=0.003)。和CC基因型攜帶者來比較,TT基因型攜帶者的胃癌癌前病變的發(fā)病風險有所增加,其中(OR=1.840,95%CI:1.174~2.886)。和Hp感染為陰性同時為CC+CT基因型者作比較,單一攜帶TT基因型稍微(OR=1.783,95%CI:0.9004~3.530)增加胃癌癌前病變的發(fā)病風險,然而單一的Hp感染卻會讓發(fā)病的風險增加(OR=2.389,95%CI:1.799~3.173),同時具有Hp感染和攜帶TT基因型(OR=3.335,95%CI:1.935~5.749)可以使胃癌癌前病變的發(fā)病風險顯著增加,兩種因素聯合的作用相對比較明顯。研究結論在青島地區(qū)的常住漢族人群中PSCArs2294008位點基因多態(tài)性在病例組和健康對照組中分布差異具有統(tǒng)計學意義,同時和胃粘膜相關性疾病腸上皮化生、上皮內瘤變的易感性存在一定的關聯,Hp感染可以讓PSCA rs2294008 TT基因型攜帶者發(fā)生腸上皮化生、上皮內瘤變的危險性進一步增加。
[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.

【學位授予單位】:大連醫(yī)科大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R735.2

【參考文獻】

相關期刊論文 前2條

1 Hyo Jun Ahn;Dong Soo Lee;;Helicobacter pylori in gastric carcinogenesis[J];World Journal of Gastrointestinal Oncology;2015年12期

2 Wanqing Chen;Rongshou Zheng;Hongmei Zeng;Siwei Zhang;;The updated incidences and mortalities of major cancers in China, 2011[J];Chinese Journal of Cancer;2015年11期

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