1887

Abstract

Polymorphic variability in the tumour-suppressor protein p53 at codon 72 has a considerable impact on cervical cancer development. The present study clarified the association between p53 codon 72 genotypes and the risk of cervical disease in Greek patients. We also examined whether the presence of specific p53 genotypes in combination with HPV16 variants or E6 T350G sequence variation can modify an individual's susceptibility to cervical disease.

The analysis of p53 genotypes was performed through PCR-RFLP. Sequence and phylogenetic tree analyses of the HPV16 E6 gene were also performed in order to identify HPV16 variants and T350G sequence variation.

The outcomes of the present analysis revealed that women who are homozygous for the arg genotype are at a 4.17-fold higher risk of developing HPV16-associated HSIL+ (OR=4.17, 95 % CI:1.48–4.9, =0.0049). Moreover, p53 arg/arg patients infected by an HPV16 prototype strain were associated with an increased risk of more severe lesions, while a significant relationship between the p53 arg/arg genotype in patients with T350G sequence variation and the risk of high-grade squamous intraepithelial lesions (HSILs) was revealed.

The oncogenic potential of the virus is increased by the presence of the p53 arg/arg genotype in the Greek population in such a way that the specific protein interaction E6 (L83V)–p53 (Arg-72) can modify an individual's susceptibility to cervical disease.

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2017-09-01
2024-03-28
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References

  1. Zur Hausen H. Papillomavirus infections — a major cause of human cancers. Biochimica Et Biophysica Acta 1996; 1288:F55–F78 [View Article]
    [Google Scholar]
  2. Chiantore MV, Vannucchi S, Accardi R, Tommasino M, Percario ZA et al. Interferon-β induces cellular senescence in cutaneous human papilloma virus-transformed human keratinocytes by affecting p53 transactivating activity. PLoS One 2012; 7:e36909 [View Article]
    [Google Scholar]
  3. Doorbar J, Quint W, Banks L, Bravo IG, Stoler M et al. The biology and life-cycle of human papillomaviruses. Vaccine 2012; 30:F55–F70 [View Article]
    [Google Scholar]
  4. Jemal A, Bray F, Center MM, Ferlay J, Ward E et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69–90 [View Article]
    [Google Scholar]
  5. Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J et al. Global burden of human papillomavirus and related diseases. Vaccine 2012; 30:F12–F23 [View Article]
    [Google Scholar]
  6. Chen Z, Terai M, Fu L, Herrero R, Desalle R et al. Diversifying selection in human papillomavirus type 16 lineages based on complete genome analyses. J Virol 2005; 79:7014–7023 [View Article]
    [Google Scholar]
  7. Chen Z, Desalle R, Schiffman M, Herrero R, Burk RD. Evolutionary dynamics of variant genomes of human papillomavirus types 18, 45, and 97. J Virol 2009; 83:1443–1455 [View Article]
    [Google Scholar]
  8. Tornesello ML, Losito S, Benincasa G, Fulciniti F, Botti G et al. Human papillomavirus (HPV) genotypes and HPV16 variants and risk of adenocarcinoma and squamous cell carcinoma of the cervix. Gynecol Oncol 2011; 121:32–42 [View Article]
    [Google Scholar]
  9. Tsakogiannis D, Papadopoulou A, Kontostathi G, Ruether IGA, Kyriakopoulou Z et al. Molecular and evolutionary analysis of HPV16 E6 and E7 genes in greek women. J Med Microbiol 2013; 62:1688–1696 [View Article]
    [Google Scholar]
  10. Cornet I, Gheit T, Iannacone MR, Vignat J, Sylla BS et al. HPV16 genetic variation and the development of cervical Cancer worldwide. Br J Cancer 2013; 108:240–244 [View Article]
    [Google Scholar]
  11. Cornet I, Gheit T, Franceschi S, Vignat J, Burk RD et al. Human papillomavirus type 16 genetic variants: phylogeny and classification based on E6 and LCR. J Virol 2012; 86:6855–6861 [View Article]
    [Google Scholar]
  12. Togtema M, Jackson R, Richard C, Niccoli S, Zehbe I. The human papillomavirus 16 European-T350G E6 variant can immortalize but not transform keratinocytes in the absence of E7. Virology 2015; 485:274–282 [View Article]
    [Google Scholar]
  13. Zhang L, Yang B, Zhang A, Zhou A, Yuan J et al. Association between human papillomavirus type 16 E6 and E7 variants with subsequent persistent infection and recurrence of cervical high-grade squamous intraepithelial lesion after conization. J Med Virol 2016; 88:1982–1988 [View Article]
    [Google Scholar]
  14. Zhang L, Liao H, Yang B, Geffre CP, Zhang A et al. Variants of human papillomavirus type 16 predispose toward persistent infection. Int J Clin Exp Pathol 2015; 8:8453–8459
    [Google Scholar]
  15. Gheit T, Cornet I, Clifford GM, Iftner T, Munk C et al. Risks for persistence and progression by human papillomavirus type 16 variant lineages among a population-based sample of Danish women. Cancer Epidemiology Biomarkers & Prevention 2011; 20:1315–1321 [View Article]
    [Google Scholar]
  16. Zehbe I, Tachezy R, Mytilineos J, Voglino G, Mikyskova I et al. Human papillomavirus 16 E6 polymorphisms in cervical lesions from different European populations polymorphisms in cervical lesions from different European populations and their correlation with human leukocyte antigen class ii haplotypes. Int J Cancer 2001; 94:711–716 [CrossRef]
    [Google Scholar]
  17. Grodzki M, Besson G, Clavel C, Arslan A, Franceschi S et al. Increased risk for cervical disease progression of French women infected with the human papillomavirus type 16 E6-350G variant. Cancer Epidemiol Biomarkers Prev 2006; 15:820–822 [View Article][PubMed]
    [Google Scholar]
  18. Martinez-Zapien D, Ruiz FX, Poirson J, Mitschler A, Ramirez J et al. Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53. Nature 2016; 529:541–545 [View Article]
    [Google Scholar]
  19. Wise-Draper TM, Wells SI. Papillomavirus E6 and E7 proteins and their cellular targets. Front Biosci 2008; 13:1003–1017 [View Article][PubMed]
    [Google Scholar]
  20. Moody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 2010; 10:550–560 [View Article]
    [Google Scholar]
  21. Burroni E, Bisanzi S, Sani C, Puliti D, Carozzi F. Codon 72 polymorphism of p53 and HPV type 16 E6 variants as risk factors for patients with squamous epithelial lesion of the uterine cervix. J Med Virol 2013; 85:83–90 [View Article]
    [Google Scholar]
  22. Li B, Wang X, Chen H, Shang LX, Wu N. TP53 codon 72 polymorphism and susceptibility to cervical cancer in the Chinese population: an update meta-analysis. Int J Clin Exp Med 2015; 8:9055–9062[PubMed]
    [Google Scholar]
  23. El Khair MM, Ennaji MM, El Kebbaj R, Mhand RA, Attaleb M et al. p53 Codon 72 polymorphism and risk of cervical carcinoma in moroccan women. Med Oncol 2010; 27:861–866 [View Article]
    [Google Scholar]
  24. Assoumou SZ, Boumba ALM, Ndjoyi-Mbiguino A, Khattabi A, Ennaji MM. The preliminary study of p53 codon 72 polymorphism and risk of cervical carcinoma in gabonese women. Med Oncol 2015; 32:281 [View Article]
    [Google Scholar]
  25. Koushik A, Platt RW, Franco EL. p53 codon 72 polymorphism and cervical neoplasia: a meta-analysis review. Cancer Epidemiol Biomarkers Prev 2004; 13:11–22 [View Article][PubMed]
    [Google Scholar]
  26. Whibley C, Pharoah PDP, Hollstein M. p53 polymorphisms: cancer implications. Nat Rev Cancer 2009; 9:95–107 [View Article]
    [Google Scholar]
  27. Storey A, Thomas M, Kalita A, Harwood C, Gardiol D et al. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 1998; 393:229–234 [CrossRef]
    [Google Scholar]
  28. Casas I, Powell L, Klapper PE, Cleator GM. New method for the extraction of viral RNA and DNA from cerebrospinal fluid for use in the polymerase chain reaction assay. J Virol Methods 1995; 53:25–36 [View Article]
    [Google Scholar]
  29. Tsakogiannis D, Ruether I, Kyriakopoulou Z, Pliaka V, Theoharopoulou A et al. Sequence variation analysis of the E2 gene of human papilloma virus type 16 in cervical lesions from women in Greece. Arch Virol 2012; 157:825–832 [View Article][PubMed]
    [Google Scholar]
  30. Tsakogiannis D, Diamantidou V, Toska E, Kyriakopoulou Z, Dimitriou TG et al. Multiplex PCR assay for the rapid identification of human papillomavirus genotypes 16, 18, 45, 35, 66, 33, 51, 58, and 31 in clinical samples. Arch Virol 2015; 160:207–214 [View Article]
    [Google Scholar]
  31. Tamura K, Dudley J, Nei M, Kumar S. MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 2007; 24:1596–1599 [View Article]
    [Google Scholar]
  32. Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 2004; 32:1792–1797 [View Article]
    [Google Scholar]
  33. Bieging KT, Mello SS, Attardi LD. Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer 2014; 14:359–370 [View Article]
    [Google Scholar]
  34. Inserra P, Abrahamsen M, Papenfuss M, Giuliano AR. Ethnic variation of the P53 codon 72 polymorphism, HPV persistence, and cervical cancer risk. Int J STD AIDS 2003; 14:800–804 [View Article]
    [Google Scholar]
  35. Malisic E, Jankovic R, Brotto K, Radulovic S. TP53 Codon 72 polymorphism and risk of cervical carcinoma in serbian women. Arch Gynecol Obstet 2013; 288:621–625 [View Article]
    [Google Scholar]
  36. Sousa H, Santos AM, Pinto D, Medeiros R. Is the p53 codon 72 polymorphism a key biomarker for cervical cancer development? A meta-analysis review within European populations. Int J Mol Med 2007; 20:731–741
    [Google Scholar]
  37. Brady CS, Varley JM, Stern PL, Duggan-Keen MF, Davidson JA. Human papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters. J Gen Virol 1999; 80:3233–3240 [View Article]
    [Google Scholar]
  38. van Duin M, Meijer CJLM, Walboomers JMM, Verheijen RHM, Helmerhorst TJ et al. Analysis of human papillomavirus type 16 E6 variants in relation to p53 Codon 72 polymorphism genotypes in cervical carcinogenesis. J Gen Virol 2000; 81:317–325 [View Article]
    [Google Scholar]
  39. Singhal P, Hussain S, Thakur N, Batra S, Salhan S et al. Association of MDM2 and p53 polymorphisms with the advancement of cervical carcinoma. DNA Cell Biol 2013; 32:19–27 [View Article]
    [Google Scholar]
  40. Eltahir HA, Elhassan AM, Ibrahim ME. Contribution of retinoblastoma LOH and the p53 Arg/Pro polymorphism to cervical cancer. Mol Med Rep 2012; 6:473–476
    [Google Scholar]
  41. Yang S-D, Cai Y-L, Jiang P, Li W, Tang J-X. Association of a miR-502-binding site single nucleotide polymorphism in the 3′-untranslated region of SET8 and the TP53 codon 72 polymorphism with cervical cancer in the Chinese population. Asian Pac J Cancer Prev 2014; 15:6505–6510 [View Article][PubMed]
    [Google Scholar]
  42. Bhattacharya P, Sengupta S. Lack of evidence that proline homozygosity at codon 72 of p53 and rare arginine allele at codon 31 of p21, jointly mediate cervical cancer susceptibility among indian women. Gynecol Oncol 2005; 99:176–182 [View Article]
    [Google Scholar]
  43. Roh JW, Kim BK, Lee CH, Kim J, Chung HH et al. P53 codon 72 and p21 codon 31 polymorphisms and susceptibility to cervical adenocarcinoma in Korean women. Oncol Res 2010; 18:453–459[PubMed] [CrossRef]
    [Google Scholar]
  44. Settheetham-Ishida W, Singto Y, Yuenyao P, Tassaneeyakul W, Kanjanavirojkul N et al. Contribution of epigenetic risk factors but not p53 Codon 72 polymorphism to the development of cervical Cancer in Northeastern Thailand. Cancer Lett 2004; 210:205–211 [View Article]
    [Google Scholar]
  45. Govan VA, Loubser S, Saleh D, Hoffman M, Williamson A-L. No relationship observed between human p53 codon-72 genotype and HPV-associated cervical cancer in a population group with a low arginine-72 allele frequency. Int J Immunogenet 2007; 34:213–217 [View Article]
    [Google Scholar]
  46. Habbous S, Pang V, Eng L, Xu W, Kurtz G et al. p53 Arg72Pro polymorphism, HPV status and initiation, progression, and development of cervical cancer: a systematic review and meta-analysis. Clin Cancer Res 2012; 18:6407–6415 [View Article][PubMed]
    [Google Scholar]
  47. Zhou X, Gu Y, Zhang SL. Association between p53 codon 72 polymorphism and cervical cancer risk among Asians: a huge review and meta-analysis. Asian Pac J Cancer Prev 2012; 13:4909–4914 [View Article][PubMed]
    [Google Scholar]
  48. Tsakogiannis D, Gartzonika C, Levidiotou-Stefanou S, Markoulatos P. Molecular approaches for HPV genotyping and HPV-DNA physical status. Expert Rev Mol Med 2017; 19:e1 [View Article][PubMed]
    [Google Scholar]
  49. Szarka K, Veress G, Juhász A, Kónya J, Sápy T et al. Integration status of virus DNA and p53 codon 72 polymorphism in human papillomavirus type 16 positive cervical cancers. Anticancer Res 2000; 20:2161–2167
    [Google Scholar]
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