Chronic inflammation and repeated infection with Opisthorchis viverrini (O. viverrini) induces intrahepatic cholangiocarcinoma (ICC). Inflammatory cytokines such as interleukin (IL) and tumor necrosis factor (TNF) are substances in the immune system that promote inflammation and causes disease to progress. Genes that help express proinflammatory cytokines can affect an individual’s susceptibility to disease, especially in cancer-related chronic inflammation. This study aimed to investigate risk factors for ICC with a focus on opisthorchiasis and polymorphisms of proinflammatory cytokines (IL-1β and TNF-α).
This study was a nested case-control study within a cohort study. 219 subjects who developed a primary ICC were identified and matched with two non-cancer controls from the same cohort based on sex and age at recruitment (±3 years). An O. viverrini-IgG antibody was assessed using enzyme linked immunosorbent assay. IL-1β and TNF-α polymorphisms were analyzed using a polymerase chain reaction with high resolution melting analysis. Associations between variables and ICC were assessed using conditional logistic regression.
Subjects with a high infection intensity had higher risk of ICC than those who had a low level (OR = 2.1; 95% CI: 1.2–3.9). Subjects with all genotypes of TNF-α (GG, GA, AA) and high infection intensity were significantly related to an increased risk of ICC (p < 0.05).
Polymorphisms of IL-1β and TNF-α are not a risk of ICC, but an individual with O. viverrini infection has an effect on all genotypes of the TNF-α gene that might promote ICC. Primary prevention of ICC in high-risk areas is based on efforts to reduce O. viverrini infection.
Khuhaprema T, Attasara P, Sriplung H, Wiangnon S, Sangkrajrang S. Cancer in Thailand, Vol. VII, 2007–2009. Bangkok: Bangkok Medical Publisher; 2013.
Pinlaor S, Ma N, Hiraku Y, Yongvanit P, Semba R, Oikawa S, et al. Repeated infection with Opisthorchis viverrini induces accumulation of 8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxyguanine in the bile duct of hamsters via inducible nitric oxide synthase. Carcinogenesis. 2004;25:1535–42. CrossRefPubMed
Techasen A, Namwat N, Loilome W, Bungkanjana P, Khuntikeo N, Puapairoj A, et al. Tumor necrosis factor-α (TNF-α) stimulates the epithelial-mesenchymal transition regulator snail in cholangiocarcinoma. Med Oncol. 2012;29:3083–91.
Al-Bahrani R, Abuetabh Y, Zeitouni N, Sergi C. Cholangiocarcinoma: risk factors. environmental influences and oncogenesis Ann Clin Lab Sci. 2013;43:195–210. PubMed
Hanada S, Harada M, Koga H, Kawaguchi T, Taniguchi E, Kumashiro R, et al. Tumor necrosis factor-alpha and interferon-gamma directly impair epithelial barrier function in cultured mouse cholangiocytes. Liver Int. 2003;23:3–11. PubMed
Komori J, Marusawa H, Machimoto T, Endo Y, Kinoshita K, Kou T, et al. Activation-induced cytidine deaminase links bile duct inflammation to human cholangiocarcinoma. Hepatology. 2008;47:888–96.
Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87:2095–147. PubMed
Wang Y, Kato N, Hoshida Y, Yoshida H, Taniguchi H, Goto T, et al. Interleukin-1beta gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection. Hepatology. 2003;37:65–71.
Yeo AET, Tanaka Y, Furuta T. Interleukin 1beta gene polymorphism and hepatitis C virus-related hepatocellular carcinoma. Hepatology. 2003;38:267–8. author reply 268–9.
Sriamporn S, Parkin DM, Pisani P, Vatanasapt V, Suwanrungruang K, Kamsa-ard P, et al. A prospective study of diet, lifestyle, and genetic factors and the risk of cancer in Khon Kaen Province, Northeast Thailand: description of the cohort. Asian Pac J Cancer Prev. 2005;6:295–303.
Songserm N, Promthet S, Sithithaworn P, Pientong C, Ekalaksananan T, Chopjitt P, et al. MTHFR polymorphisms and Opisthorchis viverrini infection: a relationship with increased susceptibility to cholangiocarcinoma in Thailand. Asian Pac J Cancer Prev. 2011;12:1341–5.
Songserm N, Promthet S, Pientong C, Ekalaksananan T, Chopjitt P, Wiangnon S. Gene-environment interaction involved in cholangiocarcinoma in the Thai population: polymorphisms of DNA repair genes, smoking and use of alcohol. BMJ Open. 2014;4:e005447.
Manwong M, Songserm N, Promthet S, Matsuo K. Risk factors for cholangiocarcinoma in the lower part of Northeast Thailand: a hospital-based case-control study. Asian Pac J Cancer Prev. 2013;14:5953–6.
Kummee P, Tangkijvanich P, Poovorawan Y, Hirankarn N. Association of HLA-DRB1*13 and TNF-alpha gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population. J Viral Hepat. 2007;14:841–8. PubMed
Heikkilä K, Harris R, Lowe G, Rumley A, Yarnell J, Gallacher J, et al. Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis. Cancer Causes Control. 2009;20:15–26.
Lech-Maranda E, Bienvenu J, Michallet A-S, Houot R, Robak T, Coiffier B, et al. Elevated IL-10 plasma levels correlate with poor prognosis in diffuse large B-cell lymphoma. Eur Cytokine Netw. 2006;17:60–6. PubMed
Heikkilä K, Ebrahim S, Lawlor DA. Systematic review of the association between circulating interleukin-6 (IL-6) and cancer. Eur J Cancer. 2008;44:937–45.
- Opisthorchiasis with proinflammatory cytokines (IL-1β and TNF-α) polymorphisms influence risk of intrahepatic cholangiocarcinoma in Thailand: a nested case-control study
- BioMed Central
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