2020-01-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/674895摘要：隨著台灣人口老化，消化道癌症其發生率、死亡率及致死率仍高，如何設計有效的個人化癌症防治策略為公共衛生之一大挑戰，幽門螺旋桿菌為胃癌之主因，針對帶菌者進行篩檢可早期診斷以改善胃癌之預後，達成次段預防的目標，此外，除菌治療可降低消化性潰瘍及功能性胃部不適，也預期將有降低日後胃癌風險之效果，因而可達成初段預防的目標。此外，目前雖已證實透過根除幽門螺旋桿菌可有效降低胃癌疾病負擔，然而，長期胃黏膜感染者即使其根除胃幽門螺旋桿菌，其後續發生胃癌的風險依然高，因此我們評估除了幽門桿菌糞便測試，再加上胃蛋白&#37238;檢驗之可行性，以及其是否可有效提供個人化的胃癌高風險篩檢方法。而對於已接受過根除幽門螺旋桿菌治療者，胃蛋白&#37238;原檢測僅能部分識別出胃癌癌前病變及胃癌風險，而表觀基因之甲基化程度檢測則與胃癌風險則呈高度相關，這些科學實證對於根除胃幽門螺旋桿菌後之胃癌防治策略考量上，若能結合血清學標記、組織學分期及表觀遺傳標記，來擬定個人化之癌症防治策略具有重要意義。此外，腸道微生物與許多人類疾病息息相關，包含有肥胖、代謝疾病、自體免疫疾病、癌症與精神及神經神經退化等疾病，因此人體腸道菌可望做為許多相關疾病生物標記，進行疾病早期診斷及防治，而改變腸道菌失衡的療法也可能成為相關疾病初段預防的方法。本計畫在彰化地區建立胃癌整合初段與次段預防篩檢模式，比較實驗組三萬人接受幽門桿菌檢查與免疫法糞便潛血檢查，以及對照組三萬人僅接受免疫法糞便潛血檢查，其後續在胃癌及大腸癌風險上之差異。我們透過衛生福利部科學資料中心資料連結，發現二合一篩檢的參與率較傳統篩檢來的高，兩組目前在發生胃癌及大腸癌比率相近，而實驗組額外獲得除菌治療的好處，以及較高的大腸腺瘤偵測率。而在胃蛋白&#37238;原檢測之隨機分派試驗，今年在彰化縣針對50至69歲民眾進行收案，總收案人數為4777人，實驗組人數為2388人，對照組人數為2389人，年齡性別在兩組無顯著差異，目前實驗組與對照組在幽門桿菌陽性率分別為38.4%及38.4%，無顯著差異，而實驗組胃蛋白&#37238;原陽性率為4.0%，預計將持續收案持續進行陽性個案轉介與除菌治療等工作；此外在馬祖社區，我們進行多次的大規模胃幽門螺旋桿菌除菌治療，我們將根據此檢測群眾資料庫，運用胃黏膜切片結果，以萎縮性性胃炎及腸化生危險分期評估系&#32479;標示癌前病變的嚴重度，量化此政策對於個人化胃癌癌前病變下降的效益，我們也連結科學資料中心的癌症登記檔，以驗證在社區大規模胃幽門螺旋桿菌根除治療後，胃癌發生率下降的效益。此外，本計畫已在彰化地區起初進行群體腸道菌相之收集，建立收集流程，並結合群體健康資料進行生物標記探勘及後續個人化癌症篩檢的應用。<br> Abstract: As population aging, the incidence, mortality, and case fatality rates of gastrointestinal tract cancers are high in Taiwan. Helicobacter pylori infection is the most important cause of gastric cancer. Not only can effectively treat peptic ulcer disease and functional dyspepsia, eradication of H. pylori has the potential to decrease the risk of gastric cancer. In this project, we evaluated the applicability and efficacy of mass screening of H. pylori infection. Besides, although H. pylori eradication has been proved that could reduce the incidence of gastric cancer, however, long-term infection could increase the risk of gastric cancer, therefore, pepsinogen test could be one of the possible additional screening tool for high risk population. As H. pylori eradication is increasingly adopted as a strategy to prevent gastric cancer, clarifying the subsequent risk for gastric cancer becomes an emerging topic. Our results indicate that gastric cancer can still occur after eradication of H. pylori infection. Under such circumstances, we find that the serological test panel is limited in predicting residual risk of gastric cancer. For those who undergo endoscopic examination, we provide a supplemental approach by using the epigenomic test. In addition, gut microbiota is closely related to many diseases, including obesity, metabolic diseases, autoimmune diseases, cancer, mental and neurodegenerative diseases. Therefore, gut microbiota may be expected to serve as biomarkers for certain diseases, and correct the imbalance of gut microbiota may also become the approach for primary prevention of related cancers in the digestive tract. We have conducted a randomized controlled trial to compare subjects who received both fecal immunochemical testing (FIT) and H. pylori stool antigen (HPSA) with those who only received FIT. The interim result showed similar rates for gastric cancer and colorectal cancer. In the HPSA+FIT group, additional benefit was gained from the cure of H. pylori-related diseases and a higher detection for colorectal adenoma. We also conducted a randomized trial to make a comparison between the strategy of H. pylori testing with and without the pepsinogen testing. We have enrolled 4777 aged between 50 and 69 in 33 screening rounds in Changhua County, including 2388 subjects in the two-test group and 2389 in the one-test group; there were no significant difference in age and sex. HPSA positivity rates were similar between two groups and the positivity rate of pepsinogen test was 4.0% in case group. We will continue the enrollment in Changhua County. In Matsu Islands, we focused on the population who has undergone mass eradication of H. pylori. We found that the pepsinogen test retained its ability in predicting atrophic gastritis after H. pylori eradication but it was limited in defining the residual risk of gastric cancer because of extensive premalignant lesions and gastric cancers frequently found in the regressed, non-atrophic mucosae. Such a weakness could be overcome by quantifying the epigenomic damage in the gastric mucosae. In Changhua County, we also have conducted pilot program to collect gut microbiota from community population to explore biomarker surveys and the personalized cancer prevention and screening.篩檢胃癌大腸癌幽門螺旋桿菌免疫法糞便潛血檢查screeninggastric cancercolorectal cancerHelicobacter pylorifecal immunochemical testing