Skip to main content

Advertisement

SpringerLink
Log in

Polymorphism in exon 4 of TP53 gene associated to HPV 16 and 18 in Mexican women with cervical cancer

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Cervical cancer (CC) is the second most common cancer in Mexican women. Human papillomavirus (HPV) infection is necessary but not sufficient for CC development. Furthermore, genetic factors as polymorphisms could be important susceptibility factors. Controversial results regarding TP53 polymorphisms specifically in codon 72 of CC have been reported. In the present work, the exon 4 sequence of TP53 gene in CC and healthy Mexican-mestizo women were analyzed. A group of 111 women with CC and 126 healthy women (control) were included. Peripheral blood cells for polymorphism analysis and cervical scrape for HPV detection were used. PCR of exon 4 of TP53 were subjected to denaturing high-performance liquid chromatography (DHPLC) analysis and sequencing. HPV detection was subjected to PCR and sequencing. The statistical analysis was carried out using the Arlequin software. Codon 72 Arg/Arg was the most common SNP detected, and Hardy–Weinberg analysis showed equilibrium in control and CC samples (P > 0.05). Wild type sequence of TP53 exon 4 was detected in 66 and 57% in control and CC samples, respectively. For codon 72 Arg/Arg, differences between control and CC women were found (P = 0.043). An association between HPV 16/18 infection and 72 Arg/Arg in woman with CC was found (P = 0.026). Haplotype GC (codon 36 and 72) was statistically significantly associated with CC (P = 0.011). HPV 16 was the most common viral type. Codon 72 Arg/Arg is the most common polymorphism in the Mexican population and could be associated to HPV 16 and/or HPV 18 infection in CC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. http://www.inegi.org.mx/inegi/contenidos/espanol/prensa/Contenidos/estadisticas/2007/cancer07.pdf.

  2. Walboomers JM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–9.

    Article  PubMed  CAS  Google Scholar 

  3. Castellsague X, Bosch FX, Muñoz N. Environmental co-factors in HPV carcinogenesis. Virus Res. 2002;89:191.

    Article  PubMed  CAS  Google Scholar 

  4. Kirk B, Feinsod M, Favis R, Kliman RM, Barany F. Single nucleotide polymorphism seeking long term association with complex disease. Nucleic Acids Res. 2002;30:3295–311.

    Article  PubMed  CAS  Google Scholar 

  5. Storey A, et al. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature. 1998;393:229–34.

    Article  PubMed  CAS  Google Scholar 

  6. Thomas M, et al. Two Polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cel Biol. 1999;19:1092–100.

    CAS  Google Scholar 

  7. Jee SH, et al. Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis. Int J Gynaecol Obstet. 2004;85:301–8.

    Article  PubMed  CAS  Google Scholar 

  8. Makni H, et al. P53 polymorphism in codon 72 and risk of human papillomavirus-induced cervical cancer: effect of inter-laboratory variation. Int J Cancer. 2000;87:528–33.

    Article  PubMed  CAS  Google Scholar 

  9. Cohen V, et al. Evaluation of denaturing high-performance liquid chromatography as a rapid detection method for identification of epidermal growth factor receptor mutations in nonsmall-cell lung cancer. Cancer. 2006;107:2858–65.

    Article  PubMed  CAS  Google Scholar 

  10. Gross E, Kiechle M, Arnold N. Mutation analysis of p53 in ovarian tumors by DHPLC. J Biochem Biophys Methods. 2001;47:73–81.

    Article  PubMed  CAS  Google Scholar 

  11. Terris MK, Peehl DM. Human papillomavirus detection by polymerase chain reaction in benign and malignant prostate tissue is dependent on the primer set utilized. Urology. 1997;50:150–6.

    Article  PubMed  CAS  Google Scholar 

  12. Manos M. Use of polymerase chain reaction amplification for the detection of genital human papillomaviruses. In: Forth M, Greaves M, et al., editors. Cancer Cell 7º molecular diagnostics of human cancer. New York: Cold Spring Harbor Laboratory; 1988. p. 209–14.

    Google Scholar 

  13. 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;20:731–41.

    PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. Klug SJ, et al. TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol. 2009;10:772–84.

    Article  PubMed  CAS  Google Scholar 

  16. Zheng XZ, et al. Ethnicity determines association of p53Arg72Pro alleles with cervical cancer in China. Eur J Cancer Prev. 2008;17:460–6.

    Article  PubMed  CAS  Google Scholar 

  17. Suarez-Rincon AE, Moran-Moguel MC, Montoya-Fuentes H, Gallegos MP, Sánchez-Corona JL. Polymorphism in codon 72 of the p53 gene and cervico-uterine cancer risk in Mexico. Ginecol Obstet Mex. 2002;70:344–8.

    PubMed  Google Scholar 

  18. Min-Min H, Ming-Rong X, Ze-yi C, Kai-xuan Y, Zhi-lin S. Analysis of p53 codon 72 polymorphism and its association with human papillomavirus 16 and 18 E6 in Chinese cervical lesions. Int J Gynecol Cancer. 2006;16:2004–8.

    Article  PubMed  CAS  Google Scholar 

  19. Saranath D, et al. HPV16/18 prevalence in cervical lesions/cancers and p53 genotypes in cervical cancer patients from India. Gynecol Oncol. 2002;86:157–62.

    Article  PubMed  CAS  Google Scholar 

  20. Brenna SM, et al. Prognostic value of P53 codon 72 polymorphism in invasive cervical cancer in Brazil. Gynecol Oncol. 2004;93(2):374–8.

    Article  PubMed  CAS  Google Scholar 

  21. Schwartz SM, et al. Human papillomavirus and prognosis of invasive cervical cancer: a population-based study. J Clin Oncol. 2001;19:1906–15.

    PubMed  CAS  Google Scholar 

  22. Huang LW, Chao SL, Hwang JL. Human papillomavirus-31-related types predict better survival in cervical carcinoma. Cancer. 2004;100:327–34.

    Article  PubMed  Google Scholar 

  23. Shah W, et al. The prevalence of human papillomavirus type 58 in Chinese patients with cervical carcinoma and its influence on survival. Clin Oncol (R Coll Radiol). 2009;21:768–74.

    Article  Google Scholar 

  24. Hiller T, Poppelreuther S, Stubenrauch F, Iftner T. Comparative analysis of 19 genital human papillomavirus types with regard to p53 degradation, immortalization, phylogeny, and epidemiologic risk classification. Cancer Epidemiol Biomarkers Prev. 2006;15:1262–7.

    Article  PubMed  CAS  Google Scholar 

  25. van Duin M, 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;81:317–25.

    PubMed  Google Scholar 

  26. Bergamaschi D, et al. p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. Cancer Cell. 2003;3:387–402.

    Article  PubMed  CAS  Google Scholar 

  27. Bojesen SE, Nordestgaard BG. The common germline Arg72Pro polymorphism of p53 and increased longevity in humans. Cell Cycle. 2008;7:158–63.

    Article  PubMed  CAS  Google Scholar 

  28. Koivusalo R, Hietanen S. The cytotoxicity of chemotherapy drugs varies in cervical cancer cells depending on the p53 status. Cancer Biol Ther. 2004;3:1177–83.

    Article  PubMed  CAS  Google Scholar 

  29. Varley JM, et al. Characterization of germline TP53 splicing mutations and their genetic and functional analysis. Oncogene. 2001;20:2647–54.

    Article  PubMed  CAS  Google Scholar 

  30. Tenti P, et al. p53 codon 72 polymorphism does not affect the risk of cervical cancer in patients from northern Italy. Cancer Epidemiol Biomarkers Prev. 2000;9:435–8.

    PubMed  CAS  Google Scholar 

  31. Rosenthal AN, et al. p53 codon 72 polymorphism and risk of cervical cancer in UK. Lancet. 1998;352:871–2.

    Article  PubMed  CAS  Google Scholar 

  32. Tong D, et al. Detection of p53 polymorphism at codon 72 by PCR and allele-specific oligonucleotide hybridization on microtiter plates. Clin Chem. 2000;46:124–6.

    PubMed  CAS  Google Scholar 

  33. Klug SJ, et al. TP53 Polymorphism, HPV Infection, and Risk of Cervical Cancer. Cancer Epidemiol Biomarkers Prev. 2001;10:1009–12.

    PubMed  CAS  Google Scholar 

  34. Fernandes TA, Lima GL, De Souza FC, Fernandez JV, Meissner RV. Evaluation of the polymorphisms in the exons 2 to 4 of the TP53 in cervical carcinoma patients from a Brazilian population. Mol Biol 2008; 54 Suppl: OL1025–31.

    Google Scholar 

Download references

Acknowledgments

This work was supported by grants from CONACyT 7114, and partially by SALUD-2006-COI-44633. During this work, P. Piña-Sáncez was recipient of fellowship from CONACyT and DGEP (Dirección General de Estudios de Posgrado, UNAM). This work was submitted in partial fulfillment of the requirements for the DSc degree in for P. Piña-Sánchez at Doctorado En Ciencias Biomédicas, Universidad Nacional Autonoma De Mexico. We are grateful to Psicofarma S.A. de C.V. for DHPLC equipment facilities.

Author information

Authors and Affiliations

  1. Oncology Genomic Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center SXXI-IMSS, Av. Cuauhtemoc 330, Col. Doctores, 06720, Delegación Cuauhtemoc, DF, Mexico

    Patricia Piña-Sánchez, Ana Lilia González-Herrera, Teresa Apresa-García, Guelaguetza Vázquez-Ortíz, Patricia Mendoza-Lorenzo & Mauricio Salcedo

  2. Epidemiology Division, Oncology Hospital National Medical Center 21th Century, IMSS, 06720, Delegación Cuauhtemoc, DF, Mexico

    Dulce María Hernández-Hernández

  3. Radiotherapy Service, Oncology Hospital National Medical Center 21th Century, IMSS, 06720, Delegación Cuauhtemoc, DF, Mexico

    Carlos Rodea-Avila

  4. Division of Research, National Cancer Institute, 14080, Tlalpan, DF, Mexico

    Lucia Taja-Chayeb

  5. Department of Genomic Medicine and Environmental Toxicology, Biomedical Research Institute, UNAM, Mexico, DF, Mexico

    Patricia Ostrosky-Wegman & Alfonso Dueñas-González

  6. Faculty of Nursing and Center of Research and Development of Health Sciences, UANL, 64720, Monterrey, Mexico

    Ricardo M. Cerda-Flores

Authors
  1. Patricia Piña-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dulce María Hernández-Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucia Taja-Chayeb
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ricardo M. Cerda-Flores
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana Lilia González-Herrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carlos Rodea-Avila
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Teresa Apresa-García
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Patricia Ostrosky-Wegman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Guelaguetza Vázquez-Ortíz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Patricia Mendoza-Lorenzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alfonso Dueñas-González
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mauricio Salcedo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mauricio Salcedo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Piña-Sánchez, P., Hernández-Hernández, D.M., Taja-Chayeb, L. et al. Polymorphism in exon 4 of TP53 gene associated to HPV 16 and 18 in Mexican women with cervical cancer. Med Oncol 28, 1507–1513 (2011). https://doi.org/10.1007/s12032-010-9599-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9599-8

Keywords

Search

Navigation