Genetic Variations in XRCC4 (rs1805377) and ATF6 (rs2070150) are not Associated with Hepatocellular Carcinoma in Thai Patients with Hepatitis B Virus Infection

  • Makkoch, Jarika (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) ;
  • Praianantathavorn, Kesmanee (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) ;
  • Sopipong, Watanyoo (Center of Excellent in Clinical Virology, Faculty of Medicine, Chulalongkorn University) ;
  • Chuaypen, Natthaya (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) ;
  • Tangkijvanich, Pisit (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) ;
  • Payungporn, Sunchai (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University)
  • Published : 2016.03.07


The liver is one of the most common sites of cancer in the world, hepatocellular carcinoma (HCC) predominating. Chronic hepatitis B virus infection (CHB) is considered as an important potential risk factors for HCC. Different people have diverse responses to HBV infection regarding the likelihood of HCC development, and host factors such as single nucleotide polymorphisms (SNPs) might account for this. The present study was conducted to evaluate any association between SNP frequencies in two genes, XRCC4 (rs1805377) and ATF6 (rs2070150), and the risk of CHB and HCC development in Thai patients. The study covered 369 subjects including 121 HCC patients, 141 with chronic hepatitis B virus infection (CHB) and 107 healthy controls. With TaqMan real-time PCR, the results showed that no significant association between XRCC4 (rs1805377) and ATF6 (rs2070150) and risk of HCC in the Thai population. From this first study of the 2 polymorphisms and HCC in Thailand it can concluded that rs1805377 and rs2070150 polymorphisms may not be applicable as genetic markers in the Thai population for HCC assessment.


XRCC4;rs1805377;ATF6;rs2070150;hepatocellular carcinoma;SNPs;Thailand


Supported by : Chulalongkorn University


  1. Arzumanyan A, Reis HM, Feitelson MA (2013). Pathogenic mechanisms in HBV- and HCV associated hepatocellular carcinoma. Nat Rev Cancer, 13, 123-35.
  2. Blum HE (2005). Hepatocellular carcinoma: therapy and prevention. World J Gastroenterol, 11, 7391-400.
  3. Chemin I, Zoulim F (2009). Hepatitis B virus induced hepatocellular carcinoma. Cancer Lett, 286, 52-9.
  4. Chen CJ, Chen DS (2012). Interaction of hepatitis B virus, chemical carcinogen, and genetic susceptibility: multistage hepatocarcinogenesis with multifactorial etiology. Hepatology, 36, 1046-9.
  5. Chiu CF, Tsai MH, Tseng HC, et al (2008). A novel single nucleotide polymorphism in XRCC4 gene is associated with oral cancer susceptibility in Taiwanese patients. Oral Oncol, 44, 898-902.
  6. Fels DR, Koumenis C (2006). The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth. Cancer Biol Ther, 5, 723-8.
  7. Ferlay J, Soerjomataram I, Ervik M, et al (2014). Cancer Incidence and Mortality Worldwide. In 'Globocan': International Agency for Research on Cancer, Lyon, France 2012 v1.1.
  8. Figueroa JD, Malats N, Rothman N, et al (2007). Evaluation of genetic variation in the double-strand break repair pathway and bladder cancer risk. Carcinogenesis, 28, 1788-93.
  9. Fu YP, Yu JC, Cheng TC, et al (2003). Breast cancer risk associated with genotypic polymorphism of the nonhomologous end-joining genes: a multigenic study on cancer susceptibility. Cancer Res, 63, 2440-6.
  10. Ganem D, Prince AM (2004). Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med, 350, 1118-29.
  11. Guo H, Bassig BA, Lan Q, et al (2014). Polymorphisms in DNA repair genes, hair dye use, and the risk of non-Hodgkin lymphoma. Cancer Causes Control, 25, 1261-70.
  12. Guo X, Li D, Chen Y, et al (2015). SNP rs2057482 in HIF1A gene predicts clinical outcome of aggressive hepatocellular carcinoma patients after surgery. Sci Rep, 5, 11846.
  13. Herzer K, Sprinzl MF, Galle PR (2007). Hepatitis viruses: live and let die. Liver Int, 27, 293-301.
  14. 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.
  15. Jung SW, Park NH, Shin JW, et al (2012). Polymorphisms of DNA repair genes in Korean hepatocellular carcinoma patients with chronic hepatitis B: possible implications on survival. J Hepatol, 57, 621-7.
  16. Liang TJ (2009). Hepatitis B: the virus and disease. Hepatology, 49, 13-21.
  17. Mandal RK, Singh V, Kapoor R, et al (2011). Do polymorphisms in XRCC4 influence prostate cancer susceptibility in North Indian population? Biomarkers, 16, 236-42.
  18. Margulis V, Lin J, Yang H, et al (2008). Genetic susceptibility to renal cell carcinoma: the role of DNA double-strand break repair pathway. Cancer Epidemiol Biomarkers Prev, 17, 2366-73.
  19. Nakamoto Y, Kaneko S (2003). Mechanisms of viral hepatitis induced liver injury. Curr Mol Med, 3, 537-44.
  20. Shuda M, Kondoh N, Imazeki N, et al (2003). Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis. J Hepatol, 38, 605-14.
  21. So AY, de la Fuente E, Walter P, et al (2009). The unfolded protein response during prostate cancer development. Cancer Metastasis Rev, 28, 219-23.
  22. 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 Pacific J Cancer Prev, 14, 2865-9.
  23. 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.
  24. Suh DH, Kim MK, Kim HS, et al (2012). Unfolded protein response to autophagy as a promising druggable target for anticancer therapy. Ann N Y Acad Sci, 1271, 20-32.
  25. Thomas LF, Saetrom P (2012). Single nucleotide polymorphisms can create alternative polyadenylation signals and affect gene expression through loss of MicroRNA-Regulation. PLoS Comput Biol, 8, 1002621.
  26. Tseng HC, Tsai MH, Chiu CF, et al (2008). Association of XRCC4 codon 247 polymorphism with oral cancer susceptibility in Taiwan. Anticancer Res, 28, 1687-91.
  27. Tseng RC, Hsieh FJ, Shih CM, et al (2009). Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes: a multiple genotype-phenotype study. Cancer, 115, 2939-48.
  28. Wu X, Xin Z, Zhang W, et al (2014). A missense polymorphism in ATF6 gene is associated with susceptibility to hepatocellular carcinoma probably by altering ATF6 level. Int J Cancer, 135, 61-8.
  29. Xie CR, Sun HG, Sun Y, et al (2015). Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma. Mol Med Rep, 12, 4203-9.
  30. 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.
  31. Yang HL, Qiao DD, Li K, et al (2015). Association of genetic polymorphisms in PRKDC and XRCC4 with risk of ESCC in a high-incidence region of North China. Tumori. (Epub ahead of print)
  32. Youle Su, Songtao Qi, Changwu Dou, et al (2015). Association of LIG4 and XRCC4 gene polymorphisms with the risk of human glioma in a Chinese population. Int J Clin Exp Pathol, 8, 2057-62.
  33. Yuen MF, Hou JL, Chutaputti A (2009). Hepatocellular carcinoma in the Asia pacific region. J Gastroenterol Hepatol, 24, 346-53.
  34. Zhao P, Zou P, Zhao L, et al (2013). Genetic polymorphisms of DNA double-strand break repair pathway genes and glioma susceptibility. BMC Cancer, 13, 234.