陳建仁臺灣大學：流行病學研究所黃琇詩Huang, Hsiu-ShihHsiu-ShihHuang2007-11-272018-06-292007-11-272018-06-292005http://ntur.lib.ntu.edu.tw//handle/246246/56210目的：肝細胞癌是極為惡性之疾病，在台灣地區高居男性十大癌症死亡首位，佔女性癌症死亡第二位。歷年來肝細胞癌相關研究多著重於較好發的男性，鮮少進行女性肝細胞癌危險因子之探討，本研究係以世代研究探討肝炎病毒、抽菸、喝酒、肥胖、家族疾病史、及荷爾蒙相關因子，在女性肝細胞癌中所扮演的角色。 方法：本研究世代係參與『社區常見癌症篩檢研究計畫』(Community-Based Cancer Screening Project, CBCSP)的11920名女性個案，平均追蹤11.5年後，共有71名肝細胞癌新發個案，利用Cox 比例危險模式(Cox proportional hazards model)，針對不同病毒感染情況及可能危險因子進行單變項及多變項分析。 結果：經過人口學變項調整後，相較於B型肝炎非表面抗原帶原者，e抗原陰性與陽性的B型肝炎表面抗原帶原者，罹患肝細胞癌的相對危險性分別為2.8 (95%信賴區間：1.5-5.2) 及15.5 (95%信賴區間: 7.5-31.9)。若B型肝炎病毒DNA複製量在105 copies/mL以上，與無法測得HBV DNA之表面抗原帶原者相較，則有9倍罹患肝細胞癌的相對危險性 (95%信賴區間: 3.1-26.4)。經過多變項分析後，抽菸習慣、停經早於50歲、肥胖、及肝癌肝硬化家族史等，皆會增加女性肝細胞癌的危險性。在肝炎病毒共同感染分析中，單獨B型肝炎病毒慢性感染有16.2倍罹患肝細胞癌的相對危險性，單獨C型肝炎病毒慢性感染有18.6倍的相對危險性，而共同感染的相對危險性提高到30.2 (95%信賴區間: 8.7-105.0)。在次世代分析中，單獨B型肝炎病毒慢性感染有4.5倍罹患肝細胞癌的相對危險性，單獨人類乳突瘤病毒感染有1.3倍的相對危險性，而共同感染的相對危險性提高到14.1倍(95%信賴區間: 3.9-51.5)。 結論：在慢性肝炎病毒感染盛行的台灣，B型及C型肝炎病毒感染仍在女性肝細胞癌的發生上扮演重要的角色。抽煙、肥胖、較早停經等，也都會提高女性肝細胞癌的危險性。Objective: Hepatocellular carcinoma (HCC) is a leading malignant neoplasm with an extraordinarily high fatality. It is the first leading cancer death in men and the second leading cancer death in women in Taiwan. Most previous cohort studies on HCC risk factor were focused on males. This long-term follow-up study on a large female cohort aimed to analyze HCC risk factors including virus infection, lifestyle factors, obesity, familial disease history, and reproductive factors. Methods: From 1991 to 1992, we enrolled 11920 women with ages between 30 and 65 years from seven townships in Taiwan. Lifestyle and reproductive risk factors were collected at recruitment through a standardized personal interview based on a structured questionnaire. Blood samples collected at cohort entry were tested for HBsAg and HBeAg by radioimmunoassay, HBV DNA by polymerase chain reaction, anti-HCV by enzyme immunoassay, and HPV genotyping by genechip hybridization. The relationship of potential risk factors measured at study entry was analyzed using Cox proportional hazards model. Results: There were 71 newly-diagnosed HCC cases during 136,575 person-years of follow-up. The HCC incidence rate was 52 per 100.000 person-years. The relative risk (RR) of developing HCC was 2.8 (95% confidence interval, CI: 1.5-5.2) among women who were only HBsAg seropositive, and 15.5 (95%CI: 7.5-31.9) among those who were seropositive for both HBsAg and HBeAg in comparison with those who were seronegative on HBsAg and HBeAg. The RR of developing HCC for a serum HBV DNA level >105 copies/mL was 9.0 (95%CI: 3.1-26.4). In the multivariate analysis, statistically significant HCC risk factors other than viral infection included cigarette smoking, early menopause (<50 years), obesity, and family history of liver cirrhosis and HCC. In the analysis of interaction between HBV and HCV chronic infection, there was no synergistic effect. In the subcohort analysis of association between HCC and HPV, the RR (95% CI) were 4.5 (1.7-11.8), 1.3 (0.3-5.7), 14.1 (3.9-51.5), respectively, for only HBsAg-seropositive, only HPV DNA positive, and both positive in comparison with those without both infections. Conclusion: In Taiwan, an area endemic of chronic hepatitis virus infection, both HBV and HCV were playing a major role in the development of HCC. Cigarette smoking, early menopause and obesity were also important HCC risk factors.目錄……………………………………………………………………Ⅰ 表目錄…………………………………………………………………Ⅲ 中文摘要………………………………………………………………Ⅳ 英文摘要………………………………………………………………Ⅵ 第一章 前言............................................1 第二章 文獻探討 第一節 肝細胞癌描述流行病學............................2 第二節 肝細胞癌危險因子................................4 第三章 材料與方法 第一節 研究目的.......................................15 第二節 研究設計.......................................15 第三節 研究世代.......................................16 第四節 資料收集.......................................17 第五節 B型肝炎表面抗原及e抗原、C型肝炎抗體、人類乳突瘤病 毒測定...................................................19 第六節 資料分析.......................................21 第四章 結果 第一節 基本人口學資料.................................22 第二節 HBV與危險因子之危險性分析......................24 第三節 病毒交互作用之分析.............................35 第四節 多變項調整模式.................................41 第五章 討論...........................................43 參考文獻...............................................52403679 bytesapplication/pdfen-US女性肝細胞癌危險因子世代研究Womanhepatocellular carcinomarisk factorcohort study[SDGs]SDG3thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/56210/1/ntu-94-R92842004-1.pdf