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Epidemiologic studies on the evaluation of the prevention program against liver cancer in Saga Prefecture and on risk factors for liver cancer

佐贺县肝癌预防方案评价及肝癌危险因素的流行病学研究

基本信息

批准号：
15390188
负责人：
TANAKA Keitaro
金额：
$ 8.38万
依托单位：
Saga University (2004-2005)佐賀医科大学 (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

In this study, the main objectives were: 1) to evaluate whether the screening program for antibody to hepatitis C virus (HCV), which had been implemented in Saga Prefecture since 1993, actually contributed to lowering mortality from liver cancer; and 2) to examine the roles of both genetic factors (e.g., polymorphisms of ALDH2, ADH2, CYP1A2 and hOGG1) and environmental factors (e.g., alcohol, smoking and coffee use) in the development of hepatocellular carcinoma (HCC) from chronic hepatitis or cirrhosis. Regarding 1), we conducted an interview survey of 167 HCV carriers (participation rate: 82%), who were identified by the health screening in Saga City between 2001 and 2002. Although most carriers were attending clinics, the administration rate of interferon was low (8%), suggesting that interferon therapy may not properly be conducted by physicians. Regarding 2), we performed a case-control study of 209 HCC patients and 381 patients with chronic liver disease without HCC. As for alcohol drinking, heavy use (69 g/day or more) was strongly associated with HCC risk (odds ratio: 7.0), yet light to moderate use (less than 69 g/day) was not. Among ALDH2 heterozygotes (ALDH2^*1/^*2), however, light to moderate alcohol use was associated with an increased risk (odds ratio: 2.0), suggesting the role of acetaldehyde in hepatocarcinogenesis. As for cigarette smoking, the smoking amount during the last 5 years, in particular, was associated with an increased risk, and this association was more pronounced for wild-type homozygotes of CYP1A2 (G-2964A polymorphism) carrying high inducibility of the enzyme, indicating that cigarette smoking may be involved in the late stage of HCC development. The association between hOGG1 Ser326Cys polymorphism and HCC was not evident. Our study also suggested that coffee drinking may lower the risk of HCC (odds ratio for 3 cups/day or more: 0.5).

在这项研究中，主要目的是：1)评估佐贺县自1993年开始实施的丙型肝炎病毒抗体筛查计划是否确实有助于降低肝癌死亡率；2)研究遗传因素(如ALDH2、ADH2、CYP1A2和hOGG1的多态)和环境因素(如饮酒、吸烟和喝咖啡)在慢性肝炎或肝硬变的肝细胞癌(HCC)发生中的作用。关于1)，我们对2001年至2002年间经佐贺市健康筛查确认的167名丙型肝炎病毒携带者(参与率：82%)进行了访谈调查。虽然大多数携带者都在诊所就诊，但干扰素的使用率很低(8%)，这表明干扰素治疗可能不是由医生正确地进行的。关于2)，我们对209例肝细胞癌患者和381例非肝细胞癌的慢性肝病患者进行了病例对照研究。至于饮酒，大量饮酒(69g/天或以上)与患肝癌的风险密切相关(优势比：7.0)，而轻至中度饮酒(低于69g/天)与肝癌风险无关。然而，在ALDH2杂合子(ALDH2^*1/^*2)中，轻度到中度饮酒与增加风险相关(优势比：2.0)，这表明乙醛在肝癌发生中的作用。对于吸烟，尤其是最近5年的吸烟量与增加的风险有关，这种关联在携带高诱导性酶的野生型CYP1A2纯合子(G-2964A多态)中更为明显，提示吸烟可能参与了肝癌的晚期发展。HOGG1Ser326Cys基因多态性与肝细胞癌的相关性不明显。我们的研究还表明，喝咖啡可能会降低患肝癌的风险(每天喝3杯或更多咖啡的优势比：0.5)。