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研究生:方怡仁
研究生(外文):FANG, YI-JEN
論文名稱:石綿與腸胃道癌症之研究
論文名稱(外文):The Association of Asbestos- Exposed Workers and Gastrointestinal Cancer
指導教授:莊弘毅莊弘毅引用關係李俊賢李俊賢引用關係
指導教授(外文):CHUANG, HUNG-YILEE, JYUHN-HSIAM
口試委員:郭浩然陳保中黃以信莊弘毅杜鴻賓
口試委員(外文):GUO, HOW-RANCHEN, PAU-CHUNGHUANG, YI-SHINCHUANG, HUNG-YITU, HUNG -PIN
口試日期:2022-07-16
學位類別:博士
校院名稱:高雄醫學大學
系所名稱:環境職業醫學博士學位學程
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2022
畢業學年度:110
語文別:中文
論文頁數:90
中文關鍵詞:石棉胃癌腸胃道腫瘤職業性癌症標準化發病率
外文關鍵詞:asbestosgastric cancergastrointestinal cancersoccupational cancerstandardized incidence ratio
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石棉已被公認為與惡性間皮瘤、肺癌、喉癌和卵巢癌有關的人類致癌物。除了工人吸入石棉纖維外,經口攝入致癌纖維可能與胃腸道(GI)癌症有關,尤其是胃癌。胃癌的病因是多方面的。許多研究已確定胃癌的病因包括飲酒、醃製食品、幽門螺桿菌感染和吸菸。然而,IARC 總結了與石棉暴露相關的胃癌證據不足。胃癌與石棉暴露之間的關係仍存在爭議。
因此本研究中,我們擴大了之前的世代和追蹤時間,用台灣勞保資料庫和環境保護署(EPA)石綿監管資料庫建立了一個回顧性世代研究,以確定在1950 年至 2015 年之間從事石棉相關工作的人員的行業,並連結1980至2015年期間的台灣癌症登記資料庫(TCR),以確定個案的癌症。癌症的標準化發病率(SIR)使用台灣一般族群的胃癌發生率和參考勞動力人口計算整個石綿工人的世代SIR。與普通人群相比,石綿工人世代的胃癌SIR在男性為(1.05,95%信賴區間(95%CI)為1.02-1.09);而女性為1.10 (95% CI:1.01-1.18)。若以123個曾被確診為惡性間皮瘤病例的工作場所計算,其胃癌風險增加為1.76(95% CI:1.63-1.90)。這項針對台灣石棉接觸工人的35年回顧性隊列研究可能為職業接觸石棉與胃癌之間的關聯提供支持。
石綿相關的食道癌可能是由自由基(如活性氧)的產生和石綿纖維引起的慢性炎症引起的。根據 2006 年醫學研究所(美國)石綿委員會的描述,有關石綿與食道癌之間關聯的證據不足。進而,我們的團隊另外從 1963 年到 2017 年進行了更全面的搜索,最終納入了 34 項研究,產生了 36 個 SMR 進行統合分析。在統合分析研究中,基於 34 項世代研究定量評估了石綿暴露與食道癌之間的關係,結果表明職業或環境石綿暴露的食道癌患者的 SMR(1.28, 95% CI: 1.19-1.38)增加;也就是說,有石綿接觸史的參與者死於食道癌的可能性是普通人群的 1.28 倍。
然而,儘管對文獻進行了一些系統評價,包括一些整合分析,但石綿暴露與結直腸癌之間的關聯仍存在爭議。我們進行了系統文獻回顧,以評估接觸石綿與結直腸癌之間的關聯。系統文獻回顧,在職業接觸石綿的工人中,結直腸癌死亡率顯著增加,標準化死亡率(SMR)為 1.16(95% CI:1.05- 1.29)。在發生石綿相關的肺部癌症的工作場所中,結直腸癌的SMR為1.43(95% CI: 1.30- 1.56)。這意味著結直腸癌死亡率的風險隨著石綿暴露水平的增加而增加。
總之,我們發現在台灣石棉接觸工人的一項為期35年的世代研究中,石棉接觸工人的胃癌標準化發病率顯著升高。我們的研究結果可能為職業接觸石棉與胃癌之間的關聯提供支持。考慮到潛伏期較長,建議對包括消化道癌症(食道癌、胃癌、結腸癌)在內的癌症患者進行十年以上的追蹤。


Asbestos has been recognized as a human carcinogen associated with malignant mesothelioma, cancers of lung, larynx, and ovary.In addition to inhalation exposure to asbestos fibers among workers, oral ingestion of the carcinogenic fibers may be associated with gastrointestinal (GI) cancers, especially gastric cancer.
The etiology of gastric cancer is multifactorial. Many studies have established causes of gastric cancer include alcohol drinking, foods preserved by salting, pickled food, Helicobacter pylori infection, and tobacco smoking. However, IARC summarized an insufficient evidence for gastric cancer associated with asbestos exposure. The relationship between gastric cancer and asbestos exposure remains controversial.
In this study, we extended the previous cohort size and the follow-up period, and established a retrospective cohort using of Taiwan Labor Insurance Databases, and Environmental Protection Agency (EPA) regulatory datasets to identify those who worked in asbestos related industries between 1950 and 2015 and followed up with the Taiwan Cancer Registry (TCR) for the period 1980–2015 to identify incident the cancers, compared with the general population, Standardized incident rate (SIR) of the stomach cancer for the asbestos occupational cohort increased both in males (1.05, 95% confidence interval: 1.02–1.09 and in females 1.10 (95% CI: 1.01–1.18). The analysis supported the relationship between gastric cancer and asbestos exposure.
Based on description from Institute of Medicine (US) Committee on Asbestos in 2006, the evidence related to association between asbestos and esophageal cancer was insufficient. Thus, our research team made a more comprehensive search from 1963 to 2017, and finally included 34 studies. In the meta-analysis study, the quantitatively assessed the relationship between asbestos exposure and esophageal cancer based on 34 cohort studies, and the results demonstrated an increased SMR as 1.28 (95% CI: 1.19-1.38) in esophageal cancer patients with occupational or environmental asbestos exposure.
In addition, the association between asbestos exposure and colorectal cancer is controversial. We searched for articles on occupational asbestos exposure and colorectal cancer in PubMed, EMBASE and Web of Science. There was a systemic review showed significantly increased risk of colorectal cancer mortality among workers exposed to asbestos occupationally, with an overall pooled SMR of 1.16 (95% CI: 1.05 to 1.29). The pooled SMR for colorectal cancer was elevated in studies in which the asbestos-associated risk of lung cancer was also elevated (1.43; 95% CI: 1.30 to 1.56). These findings indicate that occupational exposure to asbestos was a risk factor for colorectal cancer.
In conclusion, we found a significantly elevated SIR of gastric cancer in asbestos-exposed workers in a 35-year cohort study of asbestos-exposed workers in Taiwan. Our findings may provide support for an association between occupational exposure to asbestos and gastric cancer. Considering the long latency period, we suggest that patients should be followed up for cancer, including gastrointestinal cancer ( esophageal cancer, stomach cancer and colon cancer) for over ten years.

摘要 i
Abstract iii
致謝 v
目錄 0
第一章 緣起 1
第二章 石綿的致癌性 3
第三章 石綿與食道癌 6
第四章 石綿與胃癌整 10
第五章 石綿與大腸癌 13
第六章 台灣本地流行病學方面的實證研究 14
第七章 石綿工廠工業衛生普查 19
第八章 分析方法 22
第九章 研究結果 27
第十章 討論 31
第十一章 結論 35
參考文獻 36
附錄: 博士學位完成之論文 PDF 51
1. Increased Risk of Gastric Cancer in Asbestos-Exposed Workers: A Retrospective Cohort Study Based on Taiwan Cancer Registry 1980–2015. Int. J. Environ. Res. Public Health 2021, 18, 7521. https://doi.org/10.3390/ijerph18147521
2. The Association of Carcinoembryonic Antigen (CEA) and Air Pollutants-A Population-Based Study. Atmosphere 2022, 13, 466. https://doi.org/10.3390/atmos13030466
3. Interaction between Single Nucleotide Polymorphisms (SNP) of Tumor Necrosis Factor-Alpha (TNF-α) Gene and Plasma Arsenic and the Effect on Estimated Glomerular Filtration Rate (eGFR). Int. J. Environ. Res. Public Health 2022, 19, 4404. https://doi.org/10.3390/ijerph19074404



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