Genetic oncological and molecular epidemiological research on development and progression of human bile duct cancer in Asia

亚洲人类胆管癌发生和进展的遗传肿瘤学和分子流行病学研究

基本信息

批准号：
15406008
负责人：
MIWA Masanao
金额：
$ 6.14万
依托单位：
Nagahama Institute of Bio-Science and Technology (2005)University of Tsukuba (2003-2004)
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

Taking advantage of collaboration with Dr.Petcharin Srivatanakul of National Cancer Institute of Thailand, we have successful cooperation with doctors and paramedical staffs in Nakorn Phanom Province, North East Thailand, and could perform a population-based case-control study of cholangiocarcinoma, in which sex, age and place of residence were matched individually. We could collect the peripheral blood and the information on the life-style related factors from the individuals who gave the informed consent.We could confirm the liver fluke infection as the risk factor. In addition we found the drinking alcohol is another independent risk factor for cholangiocarcinoma. Past and current regular drinkers of alcohol had higher risk (odds ratio=5.39[95% CI:1.11-26.06] and 4.82[95% CI:1.29-18.06], respectively). Compared to subjects who had a normal antibody range and the wild type GSTM1 gene, those who had elevated antibodies had higher odds rations of 10.34(95% CI:1.31-81.63) for wild type GSTM1 and 18.00(95% CI:3.33-97.40) for the null variant thereof, respectively. We would like to collect more samples for the case-control study to confirm the above results in the near future.On the biological characteristics of cholangiocarcinoma, we established a cholangiocarcinoma cell line, KKU 100, found that the excretory/secretory products from the liver fluke, Opisthorchis viverrini, could increase the cell proliferation of NIH-3T3 cells, and that MUC1 gene expression may be useful for predicting the poor outcome of the patients with intrahepatic cholangiocarcinoma.In addition we also established a gall bladder cancer cell line and found that MUC1 gene expression as a prognostic factor in the patients with gall bladder cancer.

利用与泰国国家癌症研究所Petcharin Srivatanakul博士的合作优势，我们与泰国东北部那空拍侬府的医生和护理人员成功合作，可以开展基于人群的胆管癌病例对照研究，其中性别、年龄和居住地均进行了单独匹配。我们可以收集知情同意者的外周血和生活方式相关因素的信息，可以确认肝吸虫感染是危险因素。此外我们发现饮酒是胆管癌的另一个独立危险因素。过去和现在经常饮酒的人风险较高（比值比分别为 5.39[95% CI:1.11-26.06] 和 4.82[95% CI:1.29-18.06]）。与抗体范围正常和野生型 GSTM1 基因的受试者相比，抗体升高的受试者野生型 GSTM1 的比值比较高，分别为 10.34（95% CI：1.31-81.63）和 18.00（95% CI：3.33-97.40） ) 分别为其空变体。我们希望在不久的将来收集更多的样本进行病例对照研究，以证实上述结果。在胆管癌的生物学特性上，我们建立了胆管癌细胞系KKU 100，发现肝脏的排泄/分泌产物吸虫 Opisthorchis viverrini 可以增加 NIH-3T3 细胞的增殖，MUC1 基因表达可能有助于预测患有吸虫病的患者的不良预后。另外我们还建立了胆囊癌细胞系，发现MUC1基因表达可以作为胆囊癌患者的预后因素。