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http://dx.doi.org/10.7314/APJCP.2014.15.13.5443

An Interleukin-6 Receptor Polymorphism is Associated with Opisthorchiasis-Linked Cholangiocarcinoma Risk in Thailand  

Prayong, Pokpong (Department of Pathology, Faculty of Medicine, Khon Kaen University)
Mairiang, Eimorn (Department of Radiology, Faculty of Medicine, Khon Kaen University)
Pairojkul, Chawalit (Department of Pathology, Faculty of Medicine, Khon Kaen University)
Chamgramol, Yaovalux (Department of Pathology, Faculty of Medicine, Khon Kaen University)
Mairiang, Pisaln (Department of Medicine, Faculty of Medicine, Khon Kaen University)
Bhudisawasdi, Vajarabhongsa (Department of Surgery, Faculty of Medicine, Khon Kaen University)
Sripa, Banchob (Department of Pathology, Faculty of Medicine, Khon Kaen University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.13, 2014 , pp. 5443-5447 More about this Journal
Abstract
The cholangiocarcinoma (CCA) is a relatively rare cancer worldwide but it is highly prevalent in Thailand where the liver fluke, Opisthorchis viverrini is endemic. There are reports that interleukin 6 (IL-6) may play an important role in the pathogenesis of opisthorchiasis associated CCA. Functionally, IL-6 can act on target cells through its receptor, IL-6R, and IL-6R polymorphisms may affect the functional activity of IL-6 leading to susceptibility to cholangiocarcinogenesis. Therefore, we assessed the association of the 48892 A/C (Asp358Ala) polymorphism in exon 9 of the IL-6R gene in 79 CCA cases compared to 80 healthy controls using the PCR-RFLP technique. The results showed significant differences between CCA cases and controls in overall genotype (p=0.001) and allele frequencies (p=0.0002). Chi-square for trend test revealed a significant association between genotype and CCA susceptibility (p=0.0002). The odds ratios (ORs) for genotype were 0.283 (95% CI=0.131-0.605, AC vs. AA; p=0.0003) and 0.206 (95% CI=0.196-1.245, CC vs. AA; p=0.0416), the OR for alleles was 0.347 (95% CI=0.187-0.633, allele C vs. allele A; p=0.0002) and that for the carrier C variant was 0.272 (95% CI=0.130-0.564; p=0.0001). This study demonstrated a close association between an IL-6R polymorphism, specifically higher A allele, and cholangiocarcinoma.
Keywords
Interleukin 6 polymorphism; cholangiocarcinoma; opisthorchiasis; PCR-RFLP;
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1 Subrungruanga I, Thawornkunob C, Chawalitchewinkoon-Petmitrc P, et al (2013). Gene expression profiling of intrahepatic cholangiocarcinoma. Asian Pac J Cancer Prev, 14, 557-63.   과학기술학회마을   DOI   ScienceOn
2 Wang H, Zhang Z, Chu W, et al (2005). Molecular screening and association analyses of the interleukin 6 receptor gene variants with type 2 diabetes, diabetic nephropathy, and insulin sensitivity. J Clin Endocrinol Metab, 90, 1123-9.   DOI
3 Wise C, Pilanthananond M, Perry BF, et al (2008). Mechanisms of biliary carcinogenesis and growth. World J Gastroenterol, 14, 2986-9.   DOI   ScienceOn
4 Wu CW, Wang SR, Chao MF, et al (1996). Serum interleukin-6 levels reflect disease status of gastric cancer. Am J Gastroenterol, 91, 1417-22.
5 Wu Q, He XD, Yu L, et al (2012). The metabolic syndrome and risk factors for biliary tract cancer: a case-control study in China. Asian Pac J Cancer Prev, 13, 1963-9.   과학기술학회마을   DOI   ScienceOn
6 Shin HR, Oh JK, Masuyer E, et al (2010). Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma--focus on East and South-Eastern Asia. Asian Pac J Cancer Prev, 11, 1159-66.
7 Park J, Tadlock L, Gores GJ, et al (1999). Inhibition of interleukin 6-mediated mitogen-activated protein kinase activation attenuates growth of a cholangiocarcinoma cell line. Hepatology, 30, 1128-33.   DOI   ScienceOn
8 Qi L, Rifai N, Hu FB (2007). Interleukin-6 receptor gene variations, plasma interleukin-6 levels, and type 2 diabetes in U.S. Women. Diabetes, 56, 3075-81.   DOI   ScienceOn
9 Reich D, Patterson N, Ramesh V, et al (2007). Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels. Am J Hum Genet, 80, 716-26.   DOI   ScienceOn
10 Sripa B, Brindley PJ, Mulvenna J, et al (2012a). The tumorigenic liver fluke Opisthorchis viverrini-multiple pathways to cancer. Trends Parasitol, 28, 395-407.   DOI   ScienceOn
11 Sripa B, Kaewkes S, Sithithaworn P, et al (2007). Liver fluke induces cholangiocarcinoma. PLoS Med, 4, e201.   DOI
12 Sripa B, Mairiang E, Thinkhamrop B, et al (2009). Advanced periductal fibrosis from infection with the carcinogenic human liver fluke Opisthorchis viverrini correlates with elevated levels of interleukin-6. Hepatology, 50, 1273-81.
13 Sripa B, Pairojkul C (2008). Cholangiocarcinoma: lessons from Thailand. Cur Opin Gastroenterol, 24, 349-56.   DOI   ScienceOn
14 Sripa B, Thinkhamrop B, Mairiang E, et al (2012b). Elevated plasma IL-6 associates with increased risk of advanced fibrosis and cholangiocarcinoma in individuals infected by Opisthorchis viverrini. PLoS Negl Trop Dis, 6, e1654.   DOI
15 Malhi H, Gores GJ (2006). Cholangiocarcinoma: modern advances in understanding a deadly old disease. J Hepatol, 45, 856-67.   DOI   ScienceOn
16 Kim LH, Lee HS, Kim YJ, et al (2003). Identification of novel SNPs in the interleukin 6 receptor gene (IL6R). Hum Mutat, 21, 450-1.
17 Lamas JR, Rodriguez-Rodriguez L, Varade J, et al (2010). Influence of IL6R rs8192284 polymorphism status in disease activity in rheumatoid arthritis. J Rheumatol, 37, 1579-81.   DOI
18 Mairiang E, Laha T, Bethony JM, et al (2012). Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand. Parasitol Int, 61, 208-11.   DOI   ScienceOn
19 Marinou I, Walters K, Winfield J, et al (2010). A gain of function polymorphism in the interleukin 6 receptor influences RA susceptibility. Ann Rheum Dis, 69, 1191-4.   DOI   ScienceOn
20 Manwong M, Songserm N, Promthet S, et al (2013). Risk factors for cholangiocarcinoma in the lower part of Northeast Thailand: a hospital-based case-control study. Asian Pac J Cancer Prev, 14, 5953-6.   과학기술학회마을   DOI   ScienceOn
21 Matsumoto K, Onoyama T, Kawata S, et al (2014). Hepatitis B and C virus infection is a risk factor for the development of cholangiocarcinoma. Intern Med, 53, 651-4.   DOI
22 Mullberg J, Schooltink H, Stoyan T, et al (1993). The soluble interleukin-6 receptor is generated by shedding. Eur J Immunol, 23, 473-80.   DOI   ScienceOn
23 Ninlawan K, O'Hara SP, Splinter PL, et al (2010). Opisthorchis viverrini excretory/secretory products induce Toll-like receptor 4 upregulation and production of interleukin 6 and 8 in cholangiocyte. Parasitol Int, 59, 616-21.   DOI   ScienceOn
24 Gu F, Qureshi AA, Niu T, et al (2008). Interleukin and interleukin receptor gene polymorphisms and susceptibility to melanoma. Melanoma Res, 18, 330-5.   DOI   ScienceOn
25 Galicia JC, Tai H, Komatsu Y, et al (2006). Interleukin-6 receptor gene polymorphisms and periodontitis in a non-smoking Japanese population. J Clin Periodontol, 33, 704-9.   DOI   ScienceOn
26 Galicia JC, Tai H, Komatsu Y, et al (2004). Polymorphisms in the IL-6 receptor (IL-6R) gene: strong evidence that serum levels of soluble IL-6R are genetically influenced. Genes Immun, 5, 513-6.   DOI   ScienceOn
27 Hull J, Campino S, Rowlands K, et al (2007). Identification of common genetic variation that modulates alternative splicing. PLoS Genet, 3, 99.   DOI   ScienceOn
28 Goydos JS, Brumfield AM, Frezza E, et al (1998). Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma: validation of utility as a clinical marker. Ann Surg, 227, 398-404.   DOI   ScienceOn
29 Heinrich PC, Behrmann I, Muller-Newen G, et al (1998). Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J, 334, 297-314.   DOI
30 Huai JP, Ding J, Ye XH, et al (2014). Inflammatory bowel disease and risk of cholangiocarcinoma: evidence from a meta-analysis of population-based studies. Asian Pac J Cancer Prev, 15, 3477-82.   과학기술학회마을   DOI   ScienceOn
31 IARC (1994). Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum, 61, 121-75.
32 Jiang CQ, Lam TH, Liu B, et al (2010). Interleukin-6 receptor gene polymorphism modulates interleukin-6 levels and the metabolic syndrome: GBCS-CVD. Obesity, 18, 1969-74.   DOI   ScienceOn
33 Dosquet C, Schaetz A, Faucher C, et al (1994), Tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 in patients with renal cell carcinoma. Eur J Cancer, 30, 162-7.   DOI   ScienceOn
34 Blechacz B, Gores GJ (2008). Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment. Hepatology, 48, 308-21.
35 Bouvard V, Baan R, Straif K, et al (2009). A review of human carcinogens--Part B: biological agents. Lancet Oncol, 10, 321-2.   DOI   ScienceOn
36 Mullberg J, Oberthur W, Lottspeich F, et al (1994). The soluble human IL-6 receptor. Mutational characterization of the proteolytic cleavage site. J Immunol, 152, 4958-68.
37 Bustamante M, Nogues X, Mellibovsky L, et al (2007). Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women. Eur J Endocrinol, 157, 677-84.   DOI   ScienceOn
38 Okada S, Okusaka T, Ishii H, et al (1998). Elevated serum interleukin-6 levels in patients with pancreatic cancer. Jpn J Clin Oncol, 28, 12-5.   DOI   ScienceOn
39 Heinrich PC, Behrmann I, Haan S, et al (2003). Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J, 374, 1-20.   DOI   ScienceOn
40 Esteve E, Villuendas G, Mallolas J, et al (2006). Polymorphisms in the interleukin-6 receptor gene are associated with body mass index and with characteristics of the metabolic syndrome. Clin Endocrinol, 65, 88-91.   DOI   ScienceOn