Liver Flukes and Cholangiocarcinoma: Mechanism of Carcinogenesis

간흡충과 담관암: 발암 기전

  • Lee, Seung-Ok (Division of Gatroenterology and Hepatology, Department of Internal Medicine and Research Institute of Clinical Medicine, Chonbuk National University Hospital and Medical School) ;
  • Kim, Seong-Hun (Division of Gatroenterology and Hepatology, Department of Internal Medicine and Research Institute of Clinical Medicine, Chonbuk National University Hospital and Medical School)
  • 이승옥 (전북대학교 의학전문대학원 내과학교실, 임상연구소) ;
  • 김성훈 (전북대학교 의학전문대학원 내과학교실, 임상연구소)
  • Published : 2011.03.01

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.

Keywords

References

  1. Shin HR, Oh JK, Masuyer E, et al. Epidemiology of cholangiocarcinoma: an update focusing on risk factors. Cancer Sci 2010;101:579-585. https://doi.org/10.1111/j.1349-7006.2009.01458.x
  2. Shin HR, Oh JK, Lim MK, et al. Descriptive epidemiology of cholangiocarcinoma and clonorchiasis in Korea. J Korean Med Sci 2010;25:1011-1016. https://doi.org/10.3346/jkms.2010.25.7.1011
  3. Vennervald BJ, Polman K. Helminths and malignancy. Parasite Immunol 2009;31:686-696. https://doi.org/10.1111/j.1365-3024.2009.01163.x
  4. Fried B, Reddy A, Mayer D. Helminths in human carcinogenesis. Cancer Lett 2010 Jul 26 [Epub].
  5. Riganti M, Pungpak S, Punpoowong B, Bunnag D, Harinasuta T. Human pathology of Opisthorchis viverrini infection: a comparison of adults and children. Southeast Asian J Trop Med Public Health 1989;20:95-100.
  6. Sripa B, Kaewkes S. Gall bladder and extrahepatic bile duct changes in Opisthorchis viverrini-infected hamsters. Acta Trop 2002;83:29-36. https://doi.org/10.1016/S0001-706X(02)00052-9
  7. Sripa B, Kaewkes S, Sithithaworn P, et al. Liver fluke induces cholangiocarcinoma. PLoS Med 2007;4:e201. https://doi.org/10.1371/journal.pmed.0040201
  8. Mayer DA, Fried B. The role of helminth infections in carcinogenesis. Adv Parasitol 2007;65:239-296.
  9. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420:860-867. https://doi.org/10.1038/nature01322
  10. Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology (Williston Park) 2002;16:217-226, 229; discussion 230-232.
  11. Thamavit W, Bhamarapravati N, Sahaphong S, Vajrasthira S, Angsubhakorn S. Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini-infected Syrian golden hamsters. Cancer Res 1978;38:4634-4639.
  12. Flavell DJ, Lucas SB. Potentiation by the human liver fluke, Opisthorchis viverrini, of the carcinogenic action of N-nitrosodimethylamine upon the biliary epithelium of the hamster. Br J Cancer 1982;46:985-989. https://doi.org/10.1038/bjc.1982.313
  13. Flavell DJ, Lucas SB. Promotion of N-nitrosodimethylamine-initiated bile duct carcinogenesis in the hamster by the human liver fluke, Opisthorchis viverrini. Carcinogenesis 1983;4: 927-930. https://doi.org/10.1093/carcin/4.7.927
  14. Thamavit W, Pairojkul C, Tiwawech D, Itoh M, Shirai T, Ito N. Promotion of cholangiocarcinogenesis in the hamster liver by bile duct ligation after dimethylnitrosamine initiation. Carcinogenesis 1993;14:2415-2417. https://doi.org/10.1093/carcin/14.11.2415
  15. Thamavit W, Pairojkul C, Tiwawech D, Shirai T, Ito N. Strong promoting effect of Opisthorchis viverrini infection on dimethylnitrosamine-initiated hamster liver. Cancer Lett 1994;78: 121-125. https://doi.org/10.1016/0304-3835(94)90040-X
  16. Lee JH, Rim HJ, Bak UB. Effect of Clonorchis sinensis infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian golden hamsters. Korean J Parasitol 1993;31:21-30. https://doi.org/10.3347/kjp.1993.31.1.21
  17. Lee JH, Yang HM, Bak UB, Rim HJ. Promoting role of Clonorchis sinensis infection on induction of cholangiocarcinoma during two-step carcinogenesis. Korean J Parasitol 1994;32:13-18. https://doi.org/10.3347/kjp.1994.32.1.13
  18. Herrera LA, Ramirez T, Rodriguez U, et al. Possible association between Taenia solium cysticercosis and cancer: increased frequency of DNA damage in peripheral lymphocytes from neurocysticercosis patients. Trans R Soc Trop Med Hyg 2000;94:61-65. https://doi.org/10.1016/S0035-9203(00)90441-3
  19. Hudson JD, Shoaibi MA, Maestro R, Carnero A, Hannon GJ, Beach DH. A proinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med 1999;190:1375-1382. https://doi.org/10.1084/jem.190.10.1375
  20. Bhamarapravati N, Thammavit W, Vajrasthira S. Liver changes in hamsters infected with a liver fluke of man, Opisthorchis viverrini. Am J Trop Med Hyg 1978;27:787-794.
  21. Wongratanacheewin S, Bunnag D, Vaeusorn N, Sirisinha S. Characterization of humoral immune response in the serum and bile of patients with opisthorchiasis and its application in immunodiagnosis. Am J Trop Med Hyg 1988;38:356-362.
  22. Thuwajit C, Thuwajit P, Kaewkes S, et al. Increased cell proliferation of mouse fibroblast NIH-3T3 in vitro induced by excretory/secretory product(s) from Opisthorchis viverrini. Parasitology 2004;129:455-464. https://doi.org/10.1017/S0031182004005815
  23. Thuwajit C, Thuwajit P, Uchida K, et al. Gene expression profiling defined pathways correlated with fibroblast cell proliferation induced by Opisthorchis viverrini excretory/secretory product. World J Gastroenterol 2006;12:3585-3592.
  24. Sripa B, Kaewkes S. Relationship between parasite-specific antibody responses and intensity of Opisthorchis viverrini infection in hamsters. Parasite Immunol 2000;22:139-145. https://doi.org/10.1046/j.1365-3024.2000.00286.x
  25. Rim HJ. Clonorchiasis: an update. J Helminthol 2005;79:269-281. https://doi.org/10.1079/JOH2005300
  26. Pettit SJ, Seymour K, O'Flaherty E, Kirby JA. Immune selection in neoplasia: towards a microevolutionary model of cancer development. Br J Cancer 2000;82:1900-1906. https://doi.org/10.1054/bjoc.2000.1206
  27. Rubin B. Natural immunity has significant impact on immune responses against cancer. Scand J Immunol 2009;69:275-290. https://doi.org/10.1111/j.1365-3083.2008.02220.x
  28. Chang CC, Ferrone S. Immune selective pressure and HLA class I antigen defects in malignant lesions. Cancer Immunol Immunother 2007;56:227-236.
  29. Tan TT, Coussens LM. Humoral immunity, inflammation and cancer. Curr Opin Immunol 2007;19:209-216. https://doi.org/10.1016/j.coi.2007.01.001
  30. HoffmannKF, Wynn TA, Dunne DW. Cytokine-mediated host responses during schistosome infections; walking the fine line between immunological control and immunopathology. Adv Parasitol 2002;52:265-307.
  31. Dunne DW, Cooke A. A worm's eye view of the immune system: consequences for evolution of human autoimmune disease. Nat Rev Immunol 2005;5:420-426. https://doi.org/10.1038/nri1601
  32. Haswell-Elkins MR, Sithithaworn P, Mairiang E, et al. Immune responsiveness and parasite-specific antibody levels in human hepatobiliary disease associated with Opisthorchis viverrini infection. Clin Exp Immunol 1991;84:213-218.
  33. Sripa B, Kaewkes S. Localisation of parasite antigens and inflammatory responses in experimental opisthorchiasis. Int J Parasitol 2000;30:735-740. https://doi.org/10.1016/S0020-7519(00)00054-0
  34. Migasena P, Reaunsuwan W, Changbumrung S. Nitrates and nitrites in local Thai preserved protein foods. J Med Assoc Thai 1980;63:500-505.
  35. Jinawath N, Chamgramol Y, Furukawa Y, et al. Comparison of gene expression profiles between Opisthorchis viverrini and non-Opisthorchis viverrini associated human intrahepatic cholangiocarcinoma. Hepatology 2006;44:1025-1038. https://doi.org/10.1002/hep.21330
  36. Pinlaor S, Hiraku Y, Ma N, et al. Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis. Nitric Oxide 2004;11:175-183. https://doi.org/10.1016/j.niox.2004.08.004
  37. Pinlaor S, Yongvanit P, Hiraku Y, et al. 8-nitroguanine formation in the liver of hamsters infected with Opisthorchis viverrini. Biochem Biophys Res Commun 2003;309:567-571. https://doi.org/10.1016/j.bbrc.2003.08.039
  38. Satarug S, Haswell-Elkins MR, Sithithaworn P, et al. Relationships between the synthesis of N-nitrosodimethylamine and immune responses to chronic infection with the carcinogenic parasite, Opisthorchis viverrini, in men. Carcinogenesis 1998;19:485-491. https://doi.org/10.1093/carcin/19.3.485
  39. Srianujata S, Tonbuth S, Bunyaratvej S, Valyasevi A, Promvanit N, Chaivatsagul W. High urinary excretion of nitrate and N-nitrosoproline in opisthorchiasis subjects. IARC Sci Publ 1987:544-546.
  40. Srivatanakul P, Ohshima H, Khlat M, et al. Opisthorchis viverrini infestation and endogenous nitrosamines as risk factors for cholangiocarcinoma in Thailand. Int J Cancer 1991;48:821-825. https://doi.org/10.1002/ijc.2910480606
  41. Haswell-Elkins MR, Satarug S, Tsuda M, et al. Liver fluke infection and cholangiocarcinoma: model of endogenous nitric oxide and extragastric nitrosation in human carcinogenesis. Mutat Res 1994;305:241-252. https://doi.org/10.1016/0027-5107(94)90244-5
  42. Miwa M, Stuehr DJ, Marletta MA, Wishnok JS, Tannenbaum SR. Nitrosation of amines by stimulated macrophages. Carcinogenesis 1987;8:955-958. https://doi.org/10.1093/carcin/8.7.955
  43. Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 1992;89:3030-3034. https://doi.org/10.1073/pnas.89.7.3030