Prevalence of codon 72 P53 polymorphism in Brazilian women with cervix cancer

Abstract

The p53 codon 72 polymorphism seems to be associated with HPV-carcinogenesis, although controversial data have been reported. A series of Brazilian women with cervix carcinomas were analyzed. Ninety-nine (67%) of 148 women were found to be homozygous (arg/arg) for the arginine polymorphism, and 49 (33%) were heterozygous (arg/pro). This polymorphism may be an important determinant of the risk for cervix cancer, but does not seem to be sufficient for carcinogenesis. Key words: p53 polymorphism, codon 72, genetic polymorphism, cervix cancer, human papillomavirus. Cancer of the uterine cervix is the second most frequent malignancy in women in developing countries, and responsible for substantial morbidity and mortality worldwide. Almost all cervical carcinomas harbor HPV-DNA sequences, and generally the viral E6 and E7 oncoproteins are expressed in these carcinomas (Walboomers et al., 1999). The E6 and E7 of the oncogenic HPV types bind to p53 and pRb proteins, respectively. The fact that the E6 protein from the high-risk HPV can induce degradation of p53 has led to the proposal that this p53 inactivation pathway could play a key role in cervical carcinogenesis (Syrjänen and Syrjänen, 1999;Brenna and Syrjänen, 2003).Since its detection in 1987, several studies have linked genetic polymorphism of the p53 codon 72 to carcinogenesis and progression of cervical cancer. A person can carry one of two variations of the p53 gene in codon 72: either p53 arg or p53 pro. It was suggested that oncoprotein E6 inactivates p53arg(72) more easily than pro(72), bearing some association with the outcome of HPV infections. Indeed, it has been proposed that women who are homozygous for p53arg might have a higher susceptibility to the effects of oncogenic HPV types (Storey et al., 1998;Maciag and Villa, 1999, Makni et al., 2000).The material of the present study consists of 148 Brazilian women diagnosed and treated for HPV-positive invasive cervix cancer (clinical stages I-III) in two clinics: a) Maternity Hospital Leonor Mendes de Barros of the São Paulo State Health Secretariat; and b) Women's Health Care Center of the State University of Campinas. The Ethics Committees of both hospitals approved the research plan, and written informed consent was obtained from all patients. Diagnostic biopsies from all women were available for the study. The samples were fixed in formalin, embedded in paraffin, and processed for 4-µm-thick HEstained sections. The histological diagnosis of carcinoma was confirmed according to routine procedures.The demonstration of a codon 72 p53 genetic polymorphism was performed in DNA extracted from paraffin-embedded sections, using the Polymerase Chain Reaction (PCR) technique. In brief, 4-µm sections of the tumor were treated with xylene, ethanol, proteinase K, phenol and chloroform. Pellets were resuspended in milliQ water and stored at -20°C. Then, 5 µL aliquots of DNA were sub-

TP53 codon 72 polymorphism in adult soft tissue sarcomas

“…Although, no significant difference was demonstrated for the genetic and genotypic frequencies in the two groups, a higher frequency was observed for the p53Arg allele in both groups. Similar frequency patterns have been observed for different tumors (Bonafé et al, 2003;Brenna et al, 2004;Cortezzi et al, 2004;Lima et al, 2006). Our study supports the evidence that p53Arg is the most common allele in Latin American populations (Gallo et al, 2005).…”

“…Our study supports the evidence that p53Arg is the most common allele in Latin American populations (Gallo et al, 2005). However, worldwide literature data on genetic and genotypic frequencies are conflicting, due to ethnic differences among the populations studied (Brenna et al, 2004;Siddique et al, 2005). Different confounding factors should be considered as well, including sample size, the source of DNA, the detection methods, and the inter-laboratory variations in the protocols affecting the ability to detect TP53 polymorphisms (Brenna et al, 2004).…”

Evaluation of p53, p16INK4a and E-Cadherin Status as Biomarkers for Cervical Cancer Diagnosis

“…However reported data on the prevalence of p53 polymorphism in cervical cancer patients are controversial and the ethnic group characteristics seem to be an important reason for discrepancies in the frequency of this polymorphism (Brenna, 2004;Wang, 1999;Wu, 2004;Pegoraro, 2002;Klug, 2001;Szarka, 2000;Agorastos, 2000;Hildesheim, 1998;Bhattacharya, 2002). Moreover, other potential confounding factors should be also considered including the sample size, the source of DNA and the detection techniques used.…”

“…Moreover, other potential confounding factors should be also considered including the sample size, the source of DNA and the detection techniques used. Another important reason for these discrepant results could be misclassification of the p53 polymorphism, due to inter-laboratory variations in protocols, affecting the ability to detect p53 polymorphisms (Brenna, 2004;Govan, 2007;Sousa, 2007).…”

p53 codon 72 polymorphisms and random amplified polymorphic DNA analysis of non-melanoma skin cancer through archival formalin-fixed paraffin-embedded tissue

“…These findings are statistically significant suggesting that type of NMSC determine where the malignant lesion will develop; either in directly sun-exposed area or the opposite. Moreover, Brenna et al concluded that the controversial data found by the different studies have been attributed to ethnic differences, but other potential confounding factors should be considered, including the sample size, the source of DNA, and the detection techniques use (52).…”