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http://dx.doi.org/10.7314/APJCP.2015.16.18.8405

Single Nucleotide Polymorphisms in STAT3 and STAT4 and Risk of Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B  

Chanthra, Nawin (Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University)
Payungporn, Sunchai (Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University)
Chuaypen, Natthaya (Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University)
Piratanantatavorn, Kesmanee (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University)
Pinjaroen, Nutcha (Department of Radiology, Faculty of Medicine, Chulalongkorn University)
Poovorawan, Yong (Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University)
Tangkijvanich, Pisit (Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.18, 2016 , pp. 8405-8410 More about this Journal
Abstract
Hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) development. Recent studies demonstrated that single nucleotide polymorphisms (SNPs) rs2293152 in signal transducer and activator of transcription 3 (STAT3) and rs7574865 in signal transducer and activator of transcription 4 (STAT4) are associated with chronic hepatitis B (CHB)-related HCC in the Chinese population. We hypothesized that these polymorphisms might be related to HCC susceptibility in Thai population as well. Study subjects were divided into 3 groups consisting of CHB-related HCC (n=192), CHB without HCC (n=200) and healthy controls (n=190). The studied SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the distribution of different genotypes for both polymorphisms were in Hardy-Weinberg equilibrium (P>0.05). Our data demonstrated positive association of rs7574865 with HCC risk when compared to healthy controls under an additive model (GG versus TT: odds ratio (OR)=2.07, 95% confidence interval (CI)=1.06-4.03, P=0.033). This correlation remained significant under allelic and recessive models (OR=1.46, 95% CI=1.09-1.96, P=0.012 and OR=1.71, 95% CI=1.13-2.59, P=0.011, respectively). However, no significant association between rs2293152 and HCC development was observed. These data suggest that SNP rs7574865 in STAT4 might contribute to progression to HCC in the Thai population.
Keywords
Chronic hepatitis B; hepatocellular carcinoma; STAT3; STAT4; single nucleotide polymorphisms;
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1 Bruix J, Sherman M (2005). Diagnosis of Small HCC. Gastroenterology, 129, 1364.   DOI
2 Chen K, Shi W, Xin Z, et al (2013). Replication of genome wide association studies on hepatocellular carcinoma susceptibility Loci in a chinese population. PLoS One, 8, 77315.   DOI
3 Clark A, Gerlach F, Tong H, et al (2013). A trivial role of STAT4 variant in chronic hepatitis B induced hepatocellular carcinoma. Infect Genet Evol, 18, 257-61.   DOI
4 He G, Karin M (2011). NF-kappaB and STAT3-key players in liver inflammation and cancer. Cell Res, 21, 159-68.   DOI
5 He G, Yu GY, Temkin V, et al (2010). Hepatocyte IKKbeta/ NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell, 17, 286-97.   DOI
6 Hirano T, Ishihara K, Hibi M (2000). Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene, 19, 2548-56.   DOI
7 Hirschfield GM, Liu X, Xu C, et al (2009). Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N Engl J Med, 360, 2544-55.   DOI
8 Horras CJ, Lamb CL, Mitchell KA (2011). Regulation of hepatocyte fate by interferon-gamma. Cytokine Growth Factor Rev, 22, 35-43.   DOI
9 Hu K, Yang P, Jiang Z, et al (2010). STAT4 polymorphism in a Chinese Han population with Vogt-Koyanagi-Harada syndrome and Behcet's disease. Hum Immunol, 71, 723-6.   DOI
10 Hu Y, Ding N, Jin X, et al (2014). Genetic polymorphisms of STAT3 correlated with prognosis in diffuse large B-cell lymphoma patients treated with rituximab. Cancer Cell Int, 14, 25.   DOI
11 Jiang DK, Sun J, Cao G, et al (2013). Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nat Genet, 45, 72-5.   DOI
12 Kim LH, Cheong HS, Namgoong S, et al (2015). Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci of STAT4 and HLA-DQ in a Korean population. Infect Genet Evol, 33, 72-6.   DOI
13 Kimchi-Sarfaty C, Oh JM, Kim IW, et al (2007). A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science, 315, 525-8.   DOI
14 Korman BD, Kastner DL, Gregersen PK, et al (2008). STAT4: genetics, mechanisms, and implications for autoimmunity. Curr Allergy Asthma Rep, 8, 398-403.   DOI
15 Lee YH, Yun Y (1998). HBx protein of hepatitis B virus activates Jak1-STAT signaling. J Biol Chem, 273, 25510-5.   DOI
16 Nguyen KB, Watford WT, Salomon R, et al (2002). Critical role for STAT4 activation by type 1 interferons in the interferongamma response to viral infection. Science, 297, 2063-6.   DOI
17 O'Shea JJ, Holland SM, Staudt LM (2013). JAKs and STATs in immunity, immunodeficiency, and cancer. N Engl J Med, 368, 161-70.   DOI
18 Perz JF, Armstrong GL, Farrington LA, et al (2006). The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol, 45, 529-38.   DOI
19 Ramakrishna G, Rastogi A, Trehanpati N, et al (2013). From cirrhosis to hepatocellular carcinoma: new molecular insights on inflammation and cellular senescence. Liver Cancer, 2, 367-83.   DOI
20 Remmers EF, Plenge RM, Lee AT, et al (2007). STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med, 357, 977-86.   DOI
21 Saha B, Jyothi Prasanna S, Chandrasekar B, et al (2010). Gene modulation and immunoregulatory roles of interferon gamma. Cytokine, 50, 1-14.   DOI
22 Sansone P, Bromberg J (2012). Targeting the interleukin-6/ Jak/stat pathway in human malignancies. J Clin Oncol, 30, 1005-14.   DOI
23 Sato K, Shiota M, Fukuda S, et al (2009). Strong evidence of a combination polymorphism of the tyrosine kinase 2 gene and the signal transducer and activator of transcription 3 gene as a DNA-based biomarker for susceptibility to Crohn's disease in the Japanese population. J Clin Immunol, 29, 815-25.   DOI
24 Sauna ZE, Kimchi-Sarfaty C, Ambudkar SV, et al (2007). Silent polymorphisms speak: how they affect pharmacogenomics and the treatment of cancer. Cancer Res, 67, 9609-12.   DOI
25 Sopipong W, Tangkijvanich P, Payungporn S, et al (2013). The KIF1B (rs17401966) single nucleotide polymorphism is not associated with the development of HBV-related hepatocellular carcinoma in Thai patients. Asian Pac J Cancer Prev, 14, 2865-9.   DOI
26 Subramaniam A, Shanmugam MK, Perumal E, et al (2013). Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim Biophys Acta, 1835, 46-60.
27 Takeda K, Akira S (2000). STAT family of transcription factors in cytokine-mediated biological responses. Cytokine Growth Factor Rev, 11, 199-207.   DOI
28 Wang SH, Yeh SH, Lin WH, et al (2009). Identification of androgen response elements in the enhancer I of hepatitis B virus: a mechanism for sex disparity in chronic hepatitis B. Hepatology, 50, 1392-402.   DOI
29 Thierfelder WE, van Deursen JM, Yamamoto K, et al (1996). Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature, 382, 171-4.   DOI
30 Wang C, Yang W, Yan HX, et al (2012). Hepatitis B virus X (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated HBx transgenic mice. Hepatology, 55, 108-20.   DOI
31 Waris G, Siddiqui A (2002). Interaction between STAT-3 and HNF-3 leads to the activation of liver-specific hepatitis B virus enhancer 1 function. J Virol, 76, 2721-9.   DOI
32 Xie J, Zhang Y, Zhang Q, et al (2013). Interaction of signal transducer and activator of transcription 3 polymorphisms with hepatitis B virus mutations in hepatocellular carcinoma. Hepatology, 57, 2369-77.   DOI
33 Yang JD, Roberts LR (2010). Hepatocellular carcinoma: A global view. Nat Rev Gastroenterol Hepatol, 7, 448-58.   DOI
34 Yu H, Pardoll D, Jove R (2009). STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer, 9, 798-809.   DOI