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Study of p53 codon 72 polymorphism in patients with breast cancer
1Gynecology Department, Federal University of São Paulo, SP, Brazil
*Corresponding Author(s): I.D.C.G. da Silva E-mail: ismael.toco@epm.br
Breast cancer is a common disease in Western societies, with an incidence of 46.3 1/100,000 women/year in Brazil. The tumor suppressor gene TP53 is one of the most studied genes regarding the presence of mutations. Indeed, 50% of all tumors are known to exhibit changes in the TP53 nucleotide sequence due to carcinogenic processes. As to the presence of polymorphism, the TP53 gene is polymorphic at the nucleotide residue 347 (codon 72). In the current study, we examine if this polymorphism is associated with the clinicopathological parameters of breast cancer patients in a Brazilian population. One hundred and thirteen patients with breast cancer were included. The polymorphic region of the TP53 gene was PCR-amplified from genomic DNA obtained from buccal cells. Specific primers for the Pro and Arg allele were used. Correlations of polymorphism with age, staging, nuclear grade, lymph node status, estrogen receptor status and lymphatic and/or blood vessel invasion were evaluated. Statistical analysis was performed using the Fisher's exact test The frequency of p53 Arg/Arg was 57% and of the heterozygous allele Arg/Pro it was 39%. There was no correlation between polymorphism and clinicopathological parameters. According to our results, the TP53 polymorphism, at the 347 residue, is not associated with any clinicopathological findings of patients with breast cancer.
p53 polymorphism; Breast cancer; Prognosis
J.O. Vieira,I.D.C.G. da Silva,P.E.S. Higo,N.C. Nogueira-de-Souza,L.H. Gebrim. Study of p53 codon 72 polymorphism in patients with breast cancer. European Journal of Gynaecological Oncology. 2008. 29(4);364-367.
[1] ABC of breast diseases: “Breast cancer-epidemiology, risk factors and genetics”. In: Harris J.R., Lippman M.E., Morrow M., Osborne C.K. (eds.). Disease of the Breast. Philadelphia: Lippincott Williams & Wilkins, 2000, 237.
[2] Instituto Nacional do Câncer. Available at: http//: www.inca.gov.br,2005.
[3] Soulitzis N., Sourvinos G., Dokianakis D.N., Spandidos D.A.: “p53 codon 72 polymorphism and its association with bladder cancer”. Cancer Lett., 2002, 179, 175.
[4] Burns T.F., El-Deiry W.S.: “The p53 pathway and apoptosis”. J. Cell. Physiol., 1999, 181, 231.
[5] Drummond S.N., Pordeus I.A., Barbosa A.A., Gomez R.S.: “TP53 codon 72 polymorphism in oral squamous cell carcinoma”. Anticancer Res., 2002, 22, 3379.
[6] Lane D.P.: “p53 guardian of the genome”. Nature, 1992, 358, 15.
[7] Langerod A., Bukholm I.R.K., Bregard A., Lønning P.E., Andersen T.I., Rognum T.O. et al.: “The TP53 codon 72 polymorphism may affect the function of TP53 mutations in breast carcinomas but not in colorectal carcinomas”. Cancer Epidemiol., Biomark. Prev., 2002, 11, 1684.
[8] Hainaut P., Hollstein M.: “p53 and human cancer: the first ten thousand mutations”. Adv. Cancer Res., 2000, 77, 81.
[9] Shiao Y., Chen V.W., Scheer W.D., Wu X.C., Correa P.: “Racial disparity in the association of p53 gene alterations with breast cancer survival”. Cancer Res., 1995, 55, 1485.
[10] Noma C., Miyoshi Y., Taguchi T., Tamaki Y., Noguchi S.: “Association of p53 genetic polymorphism (Arg72Pro) with estrogen receptor positive breast cancer risk in Japanese women”. Cancer Lett., 2004, 210, 197.
[11] Papadakis E.N., Dokianakis D.N., Spandidos D.: “p53 codon 72 polymorphism as a risk factor in the development of breast cancer”. Mol. Cell. Biol. Res. Commun., 2000, 3, 389.
[12] Powel B.L., Staveren I.L., Roosken P., Grieu F., Berns E.M., Iacopetta B.: “Association between common polymorphisms in TP53 and p21WAF1/Cip1 and phenotypic features of breast cancer”. Carcinogenesis, 2002, 23, 311.
[13] Matlashewski G.J., Tuck S., Pim D., Lamb P., Scheider J., Crawford L.V.: “Primary structure polymorphism at amino acid residue 72 of human p53”. Mol. Cell. Biol., 1987, 7, 961.
[14] Thomas M., Kalita A., Labrecque S., Pim D., Banks L., Matlashewski G.: “Two polymorphic variants of wild-type p53 differ biochemically and biologically”. Mol. Cell. Biol., 1999, 1092.
[15] Dokianakis D.N., Spandidos D.A.: “p53 codon 72 polymorphism as a risk factor in the development of HPV-associated cervical cancer”. Mol. Cell. Biol. Res. Commun., 2000, 3, 111.
[16] Beckman G., Birgander R., Sja˘lander A., Saha N., Holmberg P.A., Kivela˘ A. et al.: “Is p53 polymorphism maintained by natural selection?”. Hum. Hered., 1994, 474, 266.
[17] Brenna S.M., Silva I.D., Zeferino L.C., Pereira J.S., Martinez E.Z., Syrja˘nen K.J.: “Prognostic value P53 codon 72 polymorphism in invasive cervical cancer in Brazil”. Gynecol. Oncol., 2004, 93, 374.
[18] Dumont P., Leu J.I., Della Pietra A.C. 3rd, George D.L., Murphy M.: “The codon 72 polymorphic variants of p53 have markedly different apoptotic potential”. Nat. Genet., 2003, 33, 357.
[19] Hildesheim A., Schiffman M., Brinton L.A., Fraumeni J.F. Jr., Herrero R., Bratti M.C. et al.: “p53 polymorphism and risk of cervical cancer”. Nature, 1998, 396, 532.
[20] Bonafé M., Ceccarelli C., Farabegoli F., Santini D., Taffurelli M., Barbi C. et al.: “Retention of the p53 codon 72 arginine allele is associated with a reduction of disease-free and overall survival in arginine/proline heterozygous breast cancer patients”. Clin. Cancer Res., 2003, 9, 4860.
[21] Furihata M., Takeuchi T., Matsumoto M., Kurabayashi A., Ohtuski Y., Terao N. et al.: “p52 mutation arising in arg72 allele in the tumorigenesis and development of carcinoma of the urinary tract”. Clin. Cancer Res., 2002, 8, 1192.
[22] Yamamoto T., Oda K., Kubota K., Miyazaki K., Takenouti Y., Nimura Y. et al.: “Expression of p73 gene, cell proliferation and apoptosis in breast cancer: immunohistochemical and clinicopathological study”. Oncol. Reports, 2002, 9, 729.
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