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간흡충과 담관암: 발암 기전

Liver Flukes and Cholangiocarcinoma: Mechanism of Carcinogenesis

김성훈|이승옥
대한내과학회 (The Korean Association Of Internal Medicine)|2011.03|대한내과학회지 (The Korean Journal of Medicine)|제80권 제3호|pp. 273-279

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간흡충; 담관암; 발암기전Liver fluke; Cholangiocarcinoma; Carcinogenesis
주제분류내과학

초록

간흡충, 즉 O. viverrini와 C. sinensis는 group I carcinogen으로 분류되어 담관암 발생과 명백한 관련이 있다. 간흡충이 담관암을 일으키는 기전에 대해서는 암 발생까지의 긴 잠복기간, 기생충 감염 정도의 다양성, 발암 물질 등 다른 인자와의 상관관계 등으로 인해 연구에 상당한 어려움이 있으나 기생충 감염 부위의 만성적인 염증과 이로 인한 미세 환경의 변화 및 DNA 손상이 발암기전의 핵심적인 특징으로 알려진다. 빨판을 부착하고 영양분을 섭취하거나 다른 부위로 이동하는 기생충에 의한 담관 손상이 만성 염증을 유발하는 것으로 보이고 간흡충이 분비 또는 배설하는 대사 산물이 담관 손상, 면역 반응 및 염증 반응 등을 일으키며 담관 상피세포의 증식 촉진효과도 가지는 것으로 보인다. 숙주의 면역 반응은 발암기전과 매우 밀접한 관계를 가지는데 장기간의 기생충 감염이 숙주의 항암 면역 반응을 억제하고 Th1-Th2 균형을 Th2 반응 쪽으로 이동을 시켜 암세포에 대한 거부 반응의 억제를 가져 오는 것도 발암 기전과 관련이 있는 것으로 보인다. 또 증가된 면역반응에서 활성화된 면역세포에서 분비된 nitric oxide 등 free radical이 DNA 손상을 일으키는 것으로 보이며 외부에서 음식물로 투여된 nitrosamine 등 발암 물질도 담관암 발생에 중요한 역할을 하는 것으로 보인다. 바이러스나 박테리아 외에 기생충도 암 발생과 분명한 관련이 있으며 최근 들어 생활 환경의 개선으로 기생충 감염률이 비록 감소하고는 있으나 치명률이 높은 담관암 발생과 밀접한 관련을 가지는 간흡충과 이의 발암기전에 대해 관심이 필요하다. 기생충 감염 민물고기 생식을 금지하는 등 기생충 감염경로 차단을 통한 유병률 감소, 적절한 진단을 통한 기생충 박멸에 노력해야 함은 물론이고, 발암기전에 대한 자세한 연구를 통해 담관암의 조기 발견을 위한 표지자 개발, 항암 물질 개발 등에 노력을 가해야 할 것으로 보인다.

Abstract

It has been clarified that chronic infection with viruses such as hepatitis B virus, bacteria such as Helicobacter pylori and parasites contribute to carcinogenesis in human. Three helminth infections have been classified as definitely carcinogenic to humans (group I carcinogens), namely Schistosoma haematobium, which is associated with urinary bladder cancer and liver flukes Clonorchis sinensis and Opisthorchis viverrini associated with cholangiocarcinoma of the liver. Opisthorchis viverrini which has been extensively studied the association with cholangiocarcinoma is endemic in Southeast Asian countries including Thailand, Vietnam and Cambodia. Clonorchis sinensis infection which is common in rural areas of Korea and China has also been reported its definite association with cholangiocarcinoma. Carcinogenesis associated with liver flukes infections is a complex process hard to be studied because of long latency period and numerous other factors can play a role although chronic inflammation has been known as a key feature. Mechanical injury from the activities of migrating and sucking flukes contributes to biliary damage and chronic inflammation. The liver fluke also secretes or excretes metabolic products, some of which are highly immunogenic, toxic and promoting biliary epithelial cell proliferation. Host immune responses and immunopathological processes are also likely associated with chronic inflammation and carcinogenesis. Escape from host anti-tumor immune response and shift to Th2 response of Th1-Th2 balance are related with carcinogenesis. Biliary cell and its DNA damage can be induced by oxygen free radicals such as nitric oxide released from effector cells activated by inflammatory cytokines. Exogenous carcinogen suchas nitrosamine seemed also closely related with cholangiocarcinoma development in liver fluke infected individuals. In this paper, various and stepwise mechanisms of carcinogenesis by liver flukes and its potential targets can be intervene were reviewed. (Korean J Med 2011; 80:273-279)

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