Kim Eun-Min, Hong Sung-Tae
Department of Microbiology, College of Medicine and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea.
Department of Tropical Medicine and Parasitology and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, Korea.
J Korean Med Sci. 2025 Apr 28;40(16):e145. doi: 10.3346/jkms.2025.40.e145.
Clonorchiasis is a parasitic disease caused by , a trematode that inhabits the intrahepatic bile ducts of humans and mammals. is one of common food-borne trematodes, prevalent in East Asia including Korea. The International Agency for Research on Cancer reclassified as the Group 1 biological carcinogen of human cholangiocarcinoma (CCA). Evidence supporting the carcinogenicity of includes epidemiological studies showing increased prevalence and odds ratio (OR) of CCA in clonorchiasis patients, the development of CCA in experimental animals, and molecular studies. Approximately 10% of CCA in Korea are believed to be solely caused by clonorchiasis, with an OR of 4.7 for CCA risk among clonorchiasis patients. All hamsters exposed to both of and N-nitrosodimethylamine (NDMA) developed CCA while those exposed to either or NDMA alone did not. In vitro studies using cell models investigated carcinogenetic changes of the intracellular molecules and genes following stimulation with a soluble extract of . The in vitro stimulated cells showed a significant shift to G2/M phage, produced oncogenic molecules, changed expression of oncogenes, increased cell proliferation and suppressed apoptosis. Additionally, the gap-junction proteins between cells, such as connexin (Cx) 43, Cx 26, and Cx 32, were changed significantly, disrupting intercellular homeostasis. These findings suggest that and nitrogen compounds synergistically stimulate the cholangiocytes to become neoplastic. is a biological carcinogen of human CCA, and the World Health Organization guidelines enlist food-borne trematodes as one of target neglected tropical diseases to be eliminated by 2030. The present article reviews and updates perspectives on clonorchiasis, focusing on carcinogenesis.
华支睾吸虫病是一种由华支睾吸虫引起的寄生虫病，华支睾吸虫是一种寄生于人和哺乳动物肝内胆管的吸虫。华支睾吸虫是常见的食源性吸虫之一，在包括韩国在内的东亚地区流行。国际癌症研究机构将华支睾吸虫重新分类为人类胆管癌（CCA）的1类生物致癌物。支持华支睾吸虫致癌性的证据包括流行病学研究显示华支睾吸虫病患者中CCA的患病率和比值比（OR）增加、实验动物中CCA的发生以及分子研究。在韩国，约10%的CCA被认为完全由华支睾吸虫病引起，华支睾吸虫病患者患CCA的风险OR为4.7。所有同时接触华支睾吸虫和N-亚硝基二甲胺（NDMA）的仓鼠都发生了CCA，而单独接触华支睾吸虫或NDMA的仓鼠则没有。使用细胞模型的体外研究调查了华支睾吸虫可溶性提取物刺激后细胞内分子和基因的致癌变化。体外刺激的细胞显示明显向G2/M期转变，产生致癌分子，改变癌基因表达，增加细胞增殖并抑制细胞凋亡。此外，细胞间的间隙连接蛋白，如连接蛋白（Cx）43、Cx 26和Cx 32，发生了显著变化，破坏了细胞间的稳态。这些发现表明，华支睾吸虫和含氮化合物协同刺激胆管细胞发生肿瘤。华支睾吸虫是人类CCA的生物致癌物，世界卫生组织的指南将食源性吸虫列为到2030年要消除的目标被忽视热带病之一。本文综述并更新了关于华支睾吸虫病的观点，重点是致癌作用。
