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World J Gastrointest Pathophysiol. Nov 15, 2014; 5(4): 570-578
Published online Nov 15, 2014. doi: 10.4291/wjgp.v5.i4.570
Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand
Masanao Miwa, Satoshi Honjo, Gyokukou You, Masakazu Tanaka, Kazuhiko Uchida, Petcharin Srivatanakul, Thiravud Khuhaprema, Watcharin Loilome, Anchalee Techasen, Chaisiri Wongkham, Temduang Limpaiboon, Puangrat Yongvanit, Sopit Wongkham
Masanao Miwa, Gyokukou You, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan
Masanao Miwa, Kazuhiko Uchida, Department of Biochemistry and Molecular Oncology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
Satoshi Honjo, Department of Pediatrics, National Hospital Organization Fukuoka National Hospital, Fukuoka 811-1394, Japan
Masakazu Tanaka, Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata City, Osaka 573-1010, Japan
Petcharin Srivatanakul, Thiravud Khuhaprema, Cancer Control Unit, National Cancer Institute, Bangkok 10400, Thailand
Watcharin Loilome, Anchalee Techasen, Chaisiri Wongkham, Puangrat Yongvanit, Sopit Wongkham, Department of Biochemistry and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Temduang Limpaiboon, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Author contributions: You G, Uchida K, Loilome W, Techasen A, Wongkham C, Limpaiboon T, Yongvanit P and Wongkham S performed the critical experiments cited in this article; Srivatanakul P and Khuhaprema T conceived the plan and collected the specimens from case and control individuals; Miwa M, Honjo S and Tanaka M analyzed the data and wrote this article.
Supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology Japan
Correspondence to: Masanao Miwa, MD, PhD, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan. m_miwa@nagahama-i-bio.ac.jp
Telephone: +81-749-648100 Fax: +81-749-648140
Received: February 11, 2014
Revised: May 1, 2014
Accepted: September 6, 2014
Published online: November 15, 2014
Abstract

Cholangiocarcinoma (CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resection. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients’ lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA.

Keywords: Alcohol drinking, Cholangiocarcinoma, DNA polymorphism, Glutathione S transferase, 8-oxoguanine glycosylase 1, Liver fluke, Opisthorchis viverrini, Thailand

Core tip: Cholangiocarcinoma (CCA) is an intractable cancer due to the difficulty of diagnosis in its early stage. The incidence of CCA in the northeast of Thailand is the highest in the world. It is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and to also detect the disease in its early stage to save patients’ lives. We analyzed the genetic and environmental determinants of risks for CCA and discussed this with the findings already published by other researchers. It is of the utmost importance to develop a non-invasive, specific and sensitive method to detect CCA.