大肠癌早诊筛查随访策略及脱氧胆酸促进肠癌发生的机制研究

发布时间：2018-06-13 18:30

本文选题：大肠癌 + 筛查策略　；参考：《昆明医科大学》2016年博士论文

【摘要】：背景：大肠癌严重危害人类健康,脱氧胆酸在大肠癌发生发展中具有一定作用。但可通过筛查和致病因素的研究达到预防、早期诊断和早期治疗,从而明显改善预后之目的。因此值得深入研究适合我国当前国情的大肠癌筛查随访策略和探索脱氧胆酸的致大肠癌作用及其机制。目的：1、研究社区人群和医院门诊人群患大肠肿瘤发病风险,探索大肠癌筛查模式及结肠镜监测随访最佳间隔时间。2、研究脱氧胆酸促大肠癌发生的作用及机制。方法：1、2011-2013年随机选取昆明安宁社区连然和金方两个街道办事处辖区内18-90(包括18岁和90岁在内)常住汉族人口3338人和昆明医科大学第一附属医院门诊就诊者2000人,通过问卷调查获取患者一般情况,经过结肠镜检查确诊是否患大肠肿瘤。分析患大肠肿瘤的危险因素,期望探索出大肠肿瘤高危问卷调查初筛出高危人群再进行结肠镜精筛的筛查模式。2、选择昆明医科大学第一附属医院消化内镜室2000年-2013年所有接受过两次以上电子结肠镜检查(如有息肉,所有检出息肉都经内镜完整切除)且保存资料完好的患者为研究对象,分析结肠镜初检正常、非腺瘤性息肉、非进展期腺瘤和进展期腺瘤患者结肠镜监测腺瘤检出／复发的危险因素和最佳随访时间间隔。3、用人正常结肠上皮细胞CCD 841 CoN和Min小鼠作为模型,观察脱氧胆酸和细胞共培养或喂养小鼠后肠粘膜细胞增殖、凋亡、Wnt信号通路蛋白(β-catenin蛋白)变化以及Min小鼠成瘤和腺瘤癌变情况。结果与结论：1、高危因素问卷调查可作为社区和门诊大肠癌筛查的初筛工具；2、大肠癌及其癌前病变的高危因素有性别、年龄、本人癌症史或肠息肉病史、慢性腹泻、慢性便秘、粘液血便、高血压、吸烟、经常吃烟熏油炸食物等。3、慢性胆囊炎和胆石症患者对大肠癌影响可能是作用于腺瘤形成之后或通过“腺瘤-癌”之外的途径；4、结肠镜监测随访检出腺瘤或腺瘤复发的危险因素有性别、年龄、息肉分布部位、腺瘤大小及位置；5、结肠镜随访监测最佳时间间隔是：初诊正常者4.76(95% CI,4.32-5.22)年,初诊为非腺瘤性息肉者3.32(95%CI,2.79-3.87)年,初诊为非进展期腺瘤者2.85(95%CI,2.53-3.17)年,初诊为进展期腺瘤者2.06(95%CI,1.71-2.45)年；6、脱氧胆酸通过β-catenin转位,活化Wnt/β-catenin信号通路,增加S期细胞、促进结肠上皮细胞增殖而起促大肠癌形成作用的。
[Abstract]:Background: colorectal cancer is a serious hazard to human health, deoxycholic acid has a certain role in the occurrence and development of colorectal cancer. However, prevention, early diagnosis and early treatment can be achieved through screening and the study of pathogenic factors, thus significantly improving the prognosis. Therefore, it is worth studying the follow-up strategy of colorectal cancer screening and exploring the mechanism of deoxycholic acid in colorectal cancer. Objective: to study the risk of colorectal cancer in community and outpatient population, to explore the screening mode of colorectal cancer and the optimal interval time of colonoscopy monitoring, and to study the role and mechanism of deoxycholic acid in promoting colorectal cancer. Methods from 2011 to 2013, 3338 residents of Han nationality (including 18 and 90 years old) and 2000 outpatients of the first affiliated Hospital of Kunming Medical University were randomly selected from Lianran and Jinfang subdistrict offices in the Anning District, Kunming, China. The general condition of the patients was obtained by questionnaire, and the colonoscopy confirmed whether the patients had colorectal tumors. To analyze the risk factors of colorectal cancer, It is expected to explore the screening model of high risk population for colonoscopy screening. 2. Select the digestive endoscopy room of the first affiliated hospital of Kunming Medical University from 2000 to 2013. Colonoscopy (if there are polyps, All patients whose polyps were completely removed by endoscope) and whose data were well preserved were analyzed for normal and nonadenomatous polyps. The risk factors for detection / recurrence of adenomas were monitored by colonoscopy in patients with non-advanced and advanced adenomas and the optimal interval of follow-up time was .3. the normal colonic epithelial cells were used as the model of CCD841 CoN and Min mice. The proliferation of intestinal mucosal cells, the changes of 尾 -catenin protein and the carcinogenesis of tumor and adenoma in Min mice were observed after co-culture or feeding of deoxycholic acid and cells. Results and conclusion 1. The questionnaire of high risk factors can be used as a screening tool for the screening of colorectal cancer in community and outpatient clinics. The high risk factors for colorectal cancer and its precancerous lesions are sex, age, history of cancer or polyp, chronic diarrhea. Chronic constipation, mucus stool, hypertension, smoking, often smoked fried food, etc., chronic cholecystitis and cholelithiasis patients may affect colorectal cancer after the formation of adenoma or through the "adenomator-cancer" pathway; 4. The risk factors of adenoma or adenoma recurrence were sex, age, distribution of polyps, size and location of adenoma. The best interval of colonoscopy was 4.7695% CI4.32-5.22). The first diagnosis of nonadenomatous polyps was 3.3295 CI2. 79-3.87), the first diagnosed non-advanced adenoma was 2. 85 / 95 CI2.53-3.17) and the first diagnosed as advanced adenoma was 2. 06 / 95CI1. 71-2.45) years. Deoxycholic acid translocated through 尾-catenin, activated Wnt/ 尾-catenin signaling pathway and increased S phase cells. Promote the proliferation of colon epithelial cells and promote the formation of colorectal cancer.
【学位授予单位】：昆明医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R735.34

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