Hepatology International

, Volume 5, Issue 3, pp 814–821 | Cite as

Serum p53 gene polymorphisms and severity of hepatitis B or C-related chronic liver diseases in Taiwan

  • Yone-Han Mah
  • Ching-Sheng Hsu
  • Chen-Hua Liu
  • Chun-Jen Liu
  • Ming-Yang Lai
  • Pei-Jer Chen
  • Ding-Shinn Chen
  • Jia-Horng Kao
Original Article


Background and aims

Polymorphisms of p53 gene are known to play an important role in hepatocarcinogenesis. We aimed to investigate the impact of p53 polymorphisms on disease progression by evaluating their prevalence among chronic hepatitis B (CHB) or hepatitis C (CHC) patients with different stages of liver disease.


A total of 215 CHB, 108 CHC patients with different stages of liver disease and 49 healthy controls were consecutively enrolled. The codon 249 p53 mutations as well as codon 72 polymorphisms were assayed by molecular methods, and their prevalence among the enrolled subjects was evaluated.


All patients and controls had codon 249 wild-type sequences. Among codon 72 sequences, Pro/Pro allele frequency of Hepatitis B-related HCC (31.4%), cirrhosis (26.9%), HBV carriers (26.3%), hepatitis C-related cirrhosis (39.1%), and CHC patients (24%) were higher than that of healthy controls (18.4%). After adjustment for sex and age, codon 72 mutant and mixed type were associated with a higher likelihood of asymptomatic carrier state than those with wild type in CHB patients [odd ratio (OR): 2.53, 95% confidence interval (CI) 1.06–6.03, P = 0.037]. However, the prevalence of codon 72 mutant and mixed type were comparable with wild type among CHC patients with HCC (OR 0.70, 95% CI 0.28–1.72, P = 0.433).


Although serum 249serine p53 mutation is rarely found in Taiwanese patients, HBV carriers have a higher prevalence of codon 72 mutants than patients with much severe liver diseases or HCV infection, which implies that codon 72 mutants may affect at an earlier stage of HBV infection. Further studies are necessary to delineate the interactions of p53 mutations with HBV infection.


p53 mutation Chronic hepatitis B or C Hepatocellular carcinoma 



Hepatitis B virus


Hepatitis C virus


Liver cirrhosis


Asymptomatic HBV carriers


Chronic persistent hepatitis


Chronic active hepatitis


Hepatocellular carcinoma


  1. 1.
    Kao JH, Chen DS. Changing disease burden of hepatocellular carcinoma in the Far East and Southeast Asia. Liver Int 2005;25:696–703PubMedCrossRefGoogle Scholar
  2. 2.
    Kao JH. Hepatitis B virus genotypes and hepatocellular carcinoma in Taiwan. Intervirology 2003;46:400–407PubMedCrossRefGoogle Scholar
  3. 3.
    Poeta ML, Manola J, Goldwasser MA, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med 2007;357:2552–2561PubMedCrossRefGoogle Scholar
  4. 4.
    Kimbi GC, Kew MC, Yu MC, Arakawa K, Hodkinson J. 249ser p53 mutation in the serum of black southern African patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2005;20:1185–1190PubMedCrossRefGoogle Scholar
  5. 5.
    Challen C, Lunec J, Warren W, Collier J, Bassendine MF. Analysis of the p53 tumor-suppressor gene in hepatocellular carcinomas from Britain. Hepatology 1992;16:1362–1366PubMedCrossRefGoogle Scholar
  6. 6.
    Coursaget P, Depril N, Chabaud M, et al. High prevalence of mutations at codon 249 of the p53 gene in hepatocellular carcinomas from Senegal. Br J Cancer 1993;67:1395–1397PubMedCrossRefGoogle Scholar
  7. 7.
    Zhu ZZ, Cong WM, Liu SF, et al. A p53 polymorphism modifies the risk of hepatocellular carcinoma among non-carriers but not carriers of chronic hepatitis B virus infection. Cancer Lett 2005;229:77–83PubMedCrossRefGoogle Scholar
  8. 8.
    Yu MW, Yang SY, Chiu YH, Chiang YC, Liaw YF, Chen CJ. A p53 genetic polymorphism as a modulator of hepatocellular carcinoma risk in relation to chronic liver disease, familial tendency, and cigarette smoking in hepatitis B carriers. Hepatology 1999;29:697–702PubMedCrossRefGoogle Scholar
  9. 9.
    Yu MW, Chen CJ. Hepatitis B and C viruses in the development of hepatocellular carcinoma. Crit Rev Oncol Hematol 1994;17:71–91PubMedCrossRefGoogle Scholar
  10. 10.
    Foulkes WD. p53—master and commander. N Engl J Med 2007;357:2539–541PubMedCrossRefGoogle Scholar
  11. 11.
    Van Dyke T. p53 and tumor suppression. N Engl J Med 2007;356:79–81PubMedCrossRefGoogle Scholar
  12. 12.
    Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature 2000;408:307–310PubMedCrossRefGoogle Scholar
  13. 13.
    Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol 2007;8:275–283PubMedCrossRefGoogle Scholar
  14. 14.
    Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994;54:4855–4878PubMedGoogle Scholar
  15. 15.
    Montesano R, Hainaut P, Wild CP. Hepatocellular carcinoma: from gene to public health. J Natl Cancer Inst 1997;89:1844–1851PubMedCrossRefGoogle Scholar
  16. 16.
    Kirk GD, Camus-Randon AM, Mendy M, et al. Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia. J Natl Cancer Inst 2000;92:148–153PubMedCrossRefGoogle Scholar
  17. 17.
    Ozturk M. p53 mutation in hepatocellular carcinoma after aflatoxin exposure. Lancet 1991;338:1356–59PubMedCrossRefGoogle Scholar
  18. 18.
    Aguilar F, Harris CC, Sun T, Hollstein M, Cerutti P. Geographic variation of p53 mutational profile in nonmalignant human liver. Science 1994;264:1317–1319PubMedCrossRefGoogle Scholar
  19. 19.
    Ming L, Thorgeirsson SS, Gail MH, et al. Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China. Hepatology 2002;36:1214–1220PubMedCrossRefGoogle Scholar
  20. 20.
    Dumont P, Leu JI, Della Pietra AC III, George DL, Murphy M. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 2003;33:357–365PubMedCrossRefGoogle Scholar
  21. 21.
    Nawroz H, Koch W, Anker P, Stroun M, Sidransky D. Microsatellite alterations in serum DNA of head and neck cancer patients. Nat Med 1996;2:1035–1037PubMedCrossRefGoogle Scholar
  22. 22.
    Aguilar F, Hussain SP, Cerutti P. Aflatoxin B1 induces the transversion of G–>T in codon 249 of the p53 tumor suppressor gene in human hepatocytes. Proc Natl Acad Sci USA 1993;90:8586–8590PubMedCrossRefGoogle Scholar
  23. 23.
    Chen XQ, Stroun M, Magnenat JL, et al. Microsatellite alterations in plasma DNA of small cell lung cancer patients. Nat Med 1996;2:1033–1035PubMedCrossRefGoogle Scholar
  24. 24.
    Wong IH, Lo YM, Zhang J, et al. Detection of aberrant p16 methylation in the plasma and serum of liver cancer patients. Cancer Res 1999;59:71–73PubMedGoogle Scholar
  25. 25.
    Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis 2002;2:395–403PubMedCrossRefGoogle Scholar
  26. 26.
    Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2001;34:1225–241PubMedCrossRefGoogle Scholar
  27. 27.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42:1208–1236PubMedCrossRefGoogle Scholar
  28. 28.
    Kao JH, Tsai SL, Chen PJ, et al. A clinicopathologic study of chronic non-A, non-B (type C) hepatitis in Taiwan: comparison between posttransfusion and sporadic patients. J Hepatol 1994;21:244–249PubMedCrossRefGoogle Scholar
  29. 29.
    Kawajiri K, Nakachi K, Imai K, Watanabe J, Hayashi SI. Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer. Carcinogenesis 1993;4:1085–1089CrossRefGoogle Scholar
  30. 30.
    Harris CC, Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 1993;329:1318–1327PubMedCrossRefGoogle Scholar
  31. 31.
    Sheen IS, Jeng KS, Wu JY. Is p53 gene mutation an indicator of the biological behaviors of recurrence of hepatocellular carcinoma? World J Gastroenterol 2003;9:1202–1207PubMedGoogle Scholar
  32. 32.
    Ding X, Park YN, Taltavull TC, et al. Geographic characterization of hepatitis virus infections, genotyping of hepatitis B virus, and p53 mutation in hepatocellular carcinoma analyzed by in situ detection of viral genomes from carcinoma tissues: comparison among six different countries. Jpn J Infect Dis 2003;56:12–18PubMedGoogle Scholar
  33. 33.
    Weston A, Pan CF, Ksieski HB, et al. p53 haplotype determination in breast cancer. Cancer Epidemiol Biomarkers Prev 1997;6:105–112PubMedGoogle Scholar
  34. 34.
    Ross RK, Yuan JM, Yu MC, et al. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 1992;339:943–946PubMedCrossRefGoogle Scholar
  35. 35.
    Wu-Williams AH, Zeise L, Thomas D. Risk assessment for aflatoxin B1: a modeling approach. Risk Anal 1992;12:559–567PubMedCrossRefGoogle Scholar
  36. 36.
    Yoon YJ, Chang HY, Han KH, et al. MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Carcinogenesis 2008;29:1192–1196PubMedCrossRefGoogle Scholar
  37. 37.
    Wang SH, Yeh SH, Lin WH, Wang HY, Chen DS, Chen PJ. Identification of androgen response elements in the enhancer I of hepatitis B virus: A mechanism for sex disparity in chronic hepatitis B. Hepatology 2009;50:1392–1402Google Scholar
  38. 38.
    Bond GL, et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 2004;119:591–602PubMedCrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2011

Authors and Affiliations

  • Yone-Han Mah
    • 1
    • 2
  • Ching-Sheng Hsu
    • 3
    • 4
    • 5
  • Chen-Hua Liu
    • 1
    • 5
  • Chun-Jen Liu
    • 1
    • 5
  • Ming-Yang Lai
    • 1
    • 5
  • Pei-Jer Chen
    • 1
    • 5
  • Ding-Shinn Chen
    • 1
    • 5
    • 6
  • Jia-Horng Kao
    • 1
    • 5
    • 6
  1. 1.Division of Gastroenterology, Department of Internal MedicineNational Taiwan University Hospital and National Taiwan University College of MedicineTaipeiTaiwan
  2. 2.Lotung St Mary’s HospitalI-LanTaiwan
  3. 3.Division of Gastroenterology, Department of Internal MedicineBuddhist Tzu Chi General HospitalTaipeiTaiwan
  4. 4.School of MedicineTzu Chi UniversityHualienTaiwan
  5. 5.Graduate Institute of Clinical MedicineNational Taiwan University College of Medicine and National Taiwan University HospitalTaipeiTaiwan
  6. 6.Hepatitis Research CenterNational Taiwan University College of Medicine and National Taiwan University HospitalTaipeiTaiwan

Personalised recommendations