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

利用与泰国国家癌症研究所的Petcharin Srivatanakul博士的合作，我们成功地与泰国东北部Nakorn Phanom省的医生和辅助医务人员合作，并可以进行基于人群的胆管癌病例对照研究，在该研究中，性别、年龄和居住地分别匹配。收集知情同意者的外周血样和生活方式相关因素信息，确认肝吸虫感染为危险因素。此外，我们还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有更高的危险性(优势比分别为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基因携带者相比，抗体升高者患野生型GSTM1的优势比分别为10.34(95%CI：1.31~81.63)和18.00(95%CI：3.33~97.40)。根据胆管癌细胞的生物学特性，我们建立了胆管癌细胞系KKU 100，发现肝吸虫的排泄/分泌产物可促进NIH-3T3细胞的增殖，MUC1基因的表达可能有助于预测肝内胆管癌患者的不良预后。此外，我们还建立了胆囊癌细胞系，发现MUC1基因表达可作为胆囊癌患者的预后因素。

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.