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Tumor Biology

, Volume 34, Issue 3, pp 1451–1459 | Cite as

Association between the p53 codon 72 Arg/Pro polymorphism and hepatocellular carcinoma risk

Research Article

Abstract

Previous studies regarding the association of p53 codon 72 Arg/Pro polymorphism with hepatocellular carcinoma (HCC) risk have provided conflicting and inconclusive findings. Thus, a meta-analysis of all currently available publications was performed to address this issue. Eleven individual case–control studies involving a total of 2,718 cases and 3,752 controls were identified after a systematic search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association of p53 codon 72 Arg/Pro polymorphism with HCC risk was estimated by the pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI). Subgroup analyses stratified by ethnicity, source of controls, gender, hepatitis virus infection status, and family history of HCC were also conducted to assess the association. Overall, significantly increased risk of HCC was identified among carriers of the homozygous genotype ProPro (ORProPro vs. ArgArg = 1.38 (95 % CI, 1.03–1.85), P OR = 0.033; ORProPro vs. ArgArg + ArgPro = 1.28 (95 % CI, 1.03–1.59), P OR = 0.026). In subgroup analysis by ethnicity, the pooled results suggested that the p53 codon 72 Arg/Pro polymorphism was associated with an increased risk of HCC in Asians and Caucasians (for Asians, ORProPro vs. ArgArg + ArgPro = 1.17 (95 % CI, 1.02–1.34), P OR = 0.025; for Caucasians, ORProPro vs. ArgArg = 1.65 (95 % CI, 1.07–2.56), P OR = 0.025; ORProPro vs. ArgArg + ArgPro = 1.74 (95 % CI, 1.14–2.66), P OR = 0.010). Subgroup analyses by source of controls and hepatitis virus infection status further demonstrated the significant association, whereas stratification factors involving gender and family history of HCC did not modify the association between p53 codon 72 Arg/Pro polymorphism and HCC risk. This meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism may play a critical role in the development of HCC, and gender and family history of HCC may not modulate the effect of p53 codon 72 Arg/Pro in HCC risk.

Keywords

P53 codon 72 Hepatocellular carcinoma Polymorphisms Meta-analysis 

Notes

Conflict of interests

None

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Shiratori Y, Yoshida H, Omata M. Management of hepatocellular carcinoma: advances in diagnosis, treatment and prevention. Expert Rev Anticancer Ther. 2001;1:277–90.PubMedCrossRefGoogle Scholar
  3. 3.
    Allen J, Venook A. Hepatocellular carcinoma: epidemic and treatment. Curr Oncol Rep. 2004;6:177–83.PubMedCrossRefGoogle Scholar
  4. 4.
    Naugler WE, Schwartz JM. Hepatocellular carcinoma. Dis Mon. 2008;54:432–44.PubMedCrossRefGoogle Scholar
  5. 5.
    Pogribny IP, Rusyn I. Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma. Cancer Lett. 2012. doi: 10.1016/j.canlet.2012.01.038.
  6. 6.
    Wong CM, Ng IO. Molecular pathogenesis of hepatocellular carcinoma. Liver Int. 2008;28:160–74.PubMedCrossRefGoogle Scholar
  7. 7.
    Yam JW, Wong CM, Ng IO. Molecular and functional genetics of hepatocellular carcinoma. Front Biosci (Schol Ed). 2010;2:117–34.CrossRefGoogle Scholar
  8. 8.
    Harris CC. p53: at the crossroads of molecular carcinogenesis and risk assessment. Science. 1993;262:1980–1.PubMedCrossRefGoogle Scholar
  9. 9.
    Dokianakis DN, Koumantaki E, Billiri K, Spandidos DA. P53 codon 72 polymorphism as a risk factor in the development of HPV-associated non-melanoma skin cancers in immunocompetent hosts. Int J Mol Med. 2000;5:405–9.PubMedGoogle Scholar
  10. 10.
    Yamashita T, Yaginuma Y, Saitoh Y, Kawai K, Kurakane T, Hayashi H, et al. Codon 72 polymorphism of p53 as a risk factor for patients with human papillomavirus-associated squamous intraepithelial lesions and invasive cancer of the uterine cervix. Carcinogenesis. 1999;20:1733–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Pandith AA, Khan NP, Rashid N, Azad N, Zaroo I, Hafiz A, et al. Impact of codon 72 Arg > Pro single nucleotide polymorphism in TP53 gene in the risk of kangri cancer: a case control study in Kashmir. Tumour Biol. 2012;33:927–33.PubMedCrossRefGoogle Scholar
  12. 12.
    Chen X, Sturgis EM, El-Naggar AK, Wei Q, Li G. Combined effects of the p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms on the risk of HPV16-associated oral cancer in never-smokers. Carcinogenesis. 2008;29:2120–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Al-Qasem A, Toulimat M, Tulbah A, Elkum N, Al-Tweigeri T, Aboussekhra A. The p53 codon 72 polymorphism is associated with risk and early onset of breast cancer among Saudi women. Oncol Lett. 2012;3:875–8.PubMedGoogle Scholar
  14. 14.
    Zhou Y, Li N, Zhuang W, Liu GJ, Wu TX, Yao X, et al. P53 codon 72 polymorphism and gastric cancer: a meta-analysis of the literature. Int J Cancer. 2007;121:1481–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Cochran WG. The comparison of percentages in matched samples. Biometrika. 1950;37:256–66.PubMedGoogle Scholar
  16. 16.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCrossRefGoogle Scholar
  17. 17.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMedGoogle Scholar
  18. 18.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.PubMedCrossRefGoogle Scholar
  19. 19.
    Stuck AE, Rubenstein LZ, Wieland D. Bias in meta-analysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity. BMJ. 1998;316:469. author reply 70–1.PubMedCrossRefGoogle Scholar
  20. 20.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.PubMedCrossRefGoogle Scholar
  21. 21.
    Sumbul AT, Akkiz H, Bayram S, Bekar A, Akgollu E, Sandikci M. p53 codon 72 polymorphism is associated with susceptibility to hepatocellular carcinoma in the Turkish population: a case–control study. Mol Biol Rep. 2012;39:1639–47.PubMedCrossRefGoogle Scholar
  22. 22.
    Di Vuolo V, Buonaguro L, Izzo F, Losito S, Botti G, Buonaguro FM, et al. TP53 and MDM2 gene polymorphisms and risk of hepatocellular carcinoma among Italian patients. Infect Agent Cancer. 2011;6:13.PubMedCrossRefGoogle Scholar
  23. 23.
    Yoon YJ, Chang HY, Ahn SH, Kim JK, Park YK, Kang DR, et al. MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Carcinogenesis. 2008;29:1192–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Ezzikouri S, El Feydi AE, Chafik A, Benazzouz M, El Kihal L, Afifi R, et al. The Pro variant of the p53 codon 72 polymorphism is associated with hepatocellular carcinoma in Moroccan population. Hepatol Res. 2007;37:748–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhu ZZ, Cong WM, Liu SF, Xian ZH, Wu WQ, Wu MC, 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;229:77–83.PubMedCrossRefGoogle Scholar
  26. 26.
    Leveri M, Gritti C, Rossi L, Zavaglia C, Civardi E, Mondelli MU, et al. Codon 72 polymorphism of P53 gene does not affect the risk of cirrhosis and hepatocarcinoma in HCV-infected patients. Cancer Lett. 2004;208:75–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Anzola M, Cuevas N, Lopez-Martinez M, Saiz A, Burgos JJ, de Pancorbo MM. Frequent loss of p53 codon 72 Pro variant in hepatitis C virus-positive carriers with hepatocellular carcinoma. Cancer Lett. 2003;193:199–205.PubMedCrossRefGoogle Scholar
  28. 28.
    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;29:697–702.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang YY, Yu HP, Fan XJ. Association of p53 codon72 polymorphism and risk of hepatocellular carcinoma. J Chin Oncol. 2012;18:189–93 [Article in Chinese].Google Scholar
  30. 30.
    Zhu ZZ, Cong WM, Zhu GS, Liu SF, Xian ZH, Wu WQ. Association of p53 codon 72 polymorphism with genetic susceptibility to hepatocellular carcinoma in Chinese population. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005;22:632–5 [Article in Chinese].PubMedGoogle Scholar
  31. 31.
    Peng T, Yan LN, Liu ZM, Shen HM, Ong CN, Peng MH, et al. Significant association of p53 codon 72 single neucletide polymorphism with hepatocellular carcinoma in Guangxi population. Chin J Surg. 2004;42:313–4 [Article in Chinese].Google Scholar
  32. 32.
    Hainaut P, Wiman KG. 30 years and a long way into p53 research. Lancet Oncol. 2009;10:913–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Francisco G, Menezes PR, Eluf-Neto J, Chammas R. Arg72Pro TP53 polymorphism and cancer susceptibility: a comprehensive meta-analysis of 302 case–control studies. Int J Cancer. 2011;129:920–30.PubMedCrossRefGoogle Scholar
  34. 34.
    Dahabreh IJ, Linardou H, Bouzika P, Varvarigou V, Murray S. TP53 Arg72Pro polymorphism and colorectal cancer risk: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010;19:1840–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 2006;6:674–87.PubMedCrossRefGoogle Scholar
  36. 36.
    Mahmood S, Niiyama G, Kamei A, Izumi A, Nakata K, Ikeda H, et al. Influence of viral load and genotype in the progression of hepatitis B-associated liver cirrhosis to hepatocellular carcinoma. Liver Int. 2005;25:220–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Chan HL, Sung JJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis. 2006;26:153–61.PubMedCrossRefGoogle Scholar
  38. 38.
    Chemin I, Zoulim F. Hepatitis B virus induced hepatocellular carcinoma. Cancer Lett. 2009;286:52–9.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Liver Transplantation CenterThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of Internal MedicinePeople’s Hospital of GaochunGaochunChina
  3. 3.Department of General SurgeryPeople’s Hospital of GaochunGaochunChina

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