Polymorphism of genes encoding drug-metabolizing and inflammation-related enzymes for susceptibility to cholangiocarcinoma in Thailand  

作　　者：Gyokukou You Lu Zeng Hideaki Tanaka Emi Ohta Takahiro Fujii Kazuhiko Ohshima Masakazu Tanaka Nobuyuki Hamajima Chutiwan Viwatthanasittiphong Mantana Muangphot Dhiraphol Chenvidhya Adisorn Jedpiyawongse Banchob Sripa Masanao Miwa Satoshi Honjo 

机构地区：[1]Department of Bioscience,Nagahama Institute of Bio-Science and Technology,Nagahama 526-0829,Shiga,Japan [2]Division of Neuroimmunology,Joint Research Center for Human Retrovirus Infection,Kagoshima University,Kagoshima 890-8544,Kagoshima,Japan [3]Department of Healthcare Administration,Nagoya University Graduate School of Medicine,Nagoya 466-8550,Aichi,Japan [4]Department of Diagnostic and Interventional Radiology,Ubon Cancer Centre,Ubon Ratchathani 34000,Thailand [5]Department of Pathology,Ubon Cancer Centre,Ubon Ratchathani 34000,Thailand [6]Department of Surgery,Ubon Cancer Centre,Ubon Ratchathani 34000,Thailand [7]Research Division,National Cancer Institute,Bangkok 10400,Thailand [8]Department of Pathology,Khon Kaen University,Khon Kaen 40002,Thailand [9]Department of Paediatirics,National Hospital Organization,Fukuoka National Hospital,Fukuoka 811-1394,Fukuoka,Japan

出　　处：《World Journal of Gastrointestinal Pathophysiology》2023年第2期21-33,共13页世界胃肠病理生理学杂志（英文版）（电子版）

基　　金：Supported by Japan Society for the Promotion of Science,No.21406011.

摘　　要：BACKGROUND Cholangiocarcinoma(CCA)is an intractable cancer,and its incidence in north eastern Thailand is the highest worldwide.Infection with the liver fluke Opisthorchis viverrini(OV)has been associated with CCA risk.However,animal experiments have suggested that OV alone does not induce CCA,but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters.Therefore,in humans,other environmental and genetic factors may also be involved.AIM To examine relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes.METHODS This hospital-based case-control study enrolled 95 case-control pairs matched by age(±5 years)and sex.We examined relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes,serum anti-OV,alcohol consumption,and smoking.Polymorphisms of CYP2E1,IL-6(-174 and-634),IL-10(-819),and NF-κB(-94)and their cooccurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed.RESULTS Although CCA risk was not significantly associated with any single polymorphism,persons with the GSTT1 wild-type and CYP2E1 c1/c2+c2/c2 genotype had an increased risk(OR=3.33,95%CI:1.23-9.00)as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype.The presence of anti-OV in serum was associated with a 7-to 11-fold increased risk,and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms.CONCLUSION In addition to infection with OV,gene-gene interactions may be considered as one of the risk factors for CCA development.

关 键 词：OPISTHORCHIS Glutathione transferase Cytochrome P-450 CYP2E1 Case-control study 

分 类 号：R735.8[医药卫生—肿瘤]