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Table of Contents
Vol. 29, No. 3, 2011
Issue release date: August 2011
Dig Dis 2011;29:278–283
(DOI:10.1159/000327559)

TGFBR3 Polymorphisms and Its Haplotypes Associated with Chronic Hepatitis B Virus Infection and Age of Hepatocellular Carcinoma Occurrence

Kim J.-H. · Yu S.J. · Park B.-L. · Cheong H.S. · Pasaje C.F.A. · Bae J.S. · Lee H.-S. · Shin H.D. · Kim Y.J.
aDepartment of Life Science, Sogang University, bDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, and cDepartment of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea

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Abstract

Objective: Hepatocellular carcinoma (HCC) is one of the most common cancers and is mainly caused by viral infections including hepatitis B virus (HBV). Recently, the decreased expression level of the transforming growth factor, beta receptor III (TGFBR3) gene, has been implicated in HCC and other human cancers. This study investigated whether TGFBR3 polymorphisms might be associated with HBV clearance and HCC occurrence. Methods: This study identified 27 single nucleotide polymorphisms (SNPs) in the exon, promoter, and exon-intron boundary regions of TGFBR3 by resequencing in 24 individuals. Then, 9 SNPs in the promoter and exons of the gene were genotyped from 1,065 Koreans composed of 637 chronic carriers (CC) and 428 spontaneously recovered (SR) subjects. Results: Two SNPs, rs1805113 (Phe676Phe) in exon 13 and rs1805117 in 3′-UTR (p = 0.009 and p = 0.008, respectively) were significantly associated with HBV clearance. In addition, Cox relative hazards analyses revealed that haplotype BL2_ht2 showed a significant association with the age of HCC occurrence among chronic HBV patients (relative hazard = 1.38; p = 0.007). Conclusion: Our findings suggest that TGFBR3 polymorphisms and its haplotypes might be associated with HBV clearance and age of HCC occurrence.



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References

  1. Nguyen VT, Law MG, Dore GJ: Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat 2009;16:453–463.
  2. Lin TM, Chen CJ, Wu MM, Yang CS, Chen JS, Lin CC, Kwang TY, Hsu ST, Lin SY, Hsu LC: Hepatitis B virus markers in Chinese twins. Anticancer Res 1989;9:737–741.
  3. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10:25–34.
  4. Ghendon Y: Perinatal transmission of hepatitis B virus in high-incidence countries. J Virol Methods 1987;17:69–79.
  5. Thursz M: Genetic susceptibility in chronic viral hepatitis. Antiviral Res 2001;52:113–116.
  6. Copland JA, Luxon BA, Ajani L, Maity T, Campagnaro E, Guo H, LeGrand SN, Tamboli P, Wood CG: Genomic profiling identifies alterations in TGF-β signaling through loss of TGF-β receptor expression in human renal cell carcinogenesis and progression. Oncogene 2003;22:8053–8062.
  7. Dong M, How T, Kirkbride KC, Gordon KJ, Lee JD, Hempel N, Kelly P, Moeller BJ, Marks JR, Blobe GC: The type III TGF-β receptor suppresses breast cancer progression. J Clin Invest 2007;117:206–217.
  8. Turley RS, Finger EC, Hempel N, How T, Fields TA, Blobe GC: The type III transforming growth factor-β receptor as a novel tumor suppressor gene in prostate cancer. Cancer Res 2007;67:1090–1098.
  9. Hersh CP, Hansel NN, Barnes KC, Lomas DA, Pillai SG, Coxson HO, Mathias RA, Rafaels NM, Wise RA, Connett JE, et al: Transforming growth factor-β receptor-3 is associated with pulmonary emphysema. Am J Respir Cell Mol Biol 2009;41:324–331.
  10. Bae HJ, Eun JW, Noh JH, Kim JK, Jung KH, Xie HJ, Park WS, Lee JY, Nam SW: Down-regulation of transforming growth factor-β receptor type III in hepatocellular carcinoma is not directly associated with genetic alterations or loss of heterozygosity. Oncol Rep 2009;22:475–480.
  11. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J: Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona 2000 EASL Conference. European Association for the Study of the Liver, 2001.
  12. Odgerel Z, Nho KB, Moon JY, Kee SH, Park KS, Song KJ, Baek LJ, Yeon JE, Byun KS, Lee CH, et al: Complete genome sequence and phylogenetic analysis of hepatitis B virus (HBV) isolates from patients with chronic HBV infection in Korea. J Med Virol 2003;71:499–503.
  13. Lieberman HM, LaBrecque DR, Kew MC, Hadziyannis SJ, Shafritz DA: Detection of hepatitis B virus DNA directly in human serum by a simplified molecular hybridization test: comparison to HBeAg/anti-HBe status in HBsAg carriers. Hepatology 1983;3:285–291.
  14. Pasche B, Knobloch TJ, Bian Y, Liu J, Phukan S, Rosman D, Kaklamani V, Baddi L, Siddiqui FS, Frankel W, et al: Somatic acquisition and signaling of TGFBR1*6A in cancer. JAMA 2005;294:1634–1646.
  15. Cui W, Fowlis DJ, Bryson S, Duffie E, Ireland H, Balmain A, Akhurst RJ: TGF-β1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 1996;86:531–542.
  16. Wollenberg GK, Semple E, Quinn BA, Hayes MA: Inhibition of proliferation of normal, preneoplastic, and neoplastic rat hepatocytes by transforming growth factor-β. Cancer Res 1987;47:6595–6599.
  17. Oft M, Heider KH, Beug H: TGF-β signaling is necessary for carcinoma cell invasiveness and metastasis. Curr Biol 1998;8:1243–1252.
  18. Park HK, Park HW, Jeon SG, Shin ES, Gho YS, Cho SH, Kim YY, Kim YK: Distinct association of genetic variations of vascular endothelial growth factor, transforming growth factor-β, and fibroblast growth factor receptors with atopy and airway hyperresponsiveness. Allergy 2008;63:447–453.
  19. Cakir M, Akcay S, Karakas T, Gedik Y, Okten A, Orhan F: Prevalence of atopy in children with type 1 diabetes mellitus, hepatitis B virus carriers, and healthy children: role of T-helper 1-type immune response. Allergy Asthma Proc 2008;29:166–170.
  20. Ferrari C, Penna A, Bertoletti A, Valli A, Antoni AD, Giuberti T, Cavalli A, Petit MA, Fiaccadori F: Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. J Immunol 1990;145:3442–3449.
  21. Mosmann TR, Coffman RL: TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145–173.
  22. Comeron JM: Selective and mutational patterns associated with gene expression in humans: influences on synonymous composition and intron presence. Genetics 2004;167:1293–1304.
  23. Plotkin JB, Robins H, Levine AJ: Tissue-specific codon usage and the expression of human genes. Proc Natl Acad Sci USA 2004;101:12588–12591.


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