P53 codon 72 polymorphism association with head and neck squamous cell carcinoma

Zahra Mojtahedi,Seyed Basir Hashemi,Bijan Khademi,Morteza Karimi,Mohammad Reza Haghshenas,Mohammad Javad Fattahi,Abbas Ghaderi

doi:10.1590/s1808-86942010000300008

Abstract

p53 tumoral suppressor gene harbors a functional polymorphism which codes either arginine (Arg) or proline (Pro) in the protein p53 of codon 72. Such polymorphism has been associated with the development or prognosis of head and neck squamous cell carcinoma (HNSCC).Aim: we assessed codon 72 p53 allelic frequencies and genotypes in HNSCC Iranian patients.Study design: Case Study.Materials and Methods: a total of 132 HNSCC patients and 123 healthy controls were genotyped. DNA source was from mononuclear cells of the peripheral blood. DNA amplification was done by means of the allele-specific polymerase chain reaction.Results: genotypes and allele distribution were not significantly different between patients and controls. Moreover, no statistically significant association was found between the 72 and p53 codon tumor location, gender or age at the time of diagnosis. However, the Pro/Pro genotype was significantly increase in stage IV patients (30.8%) when compared to stages I-III of the disease (11.1%) (p=0.03), and a significantly higher percentage of patients with the Pro allele had and a risk increase in stage IV disease (OR=2.2, 95% CI=1.2-4.2, p=0.01).Conclusion: data revealed that the p53 polymorphism do not impact the risk of HNSCC in Iranians, nonetheless, it can affect tumor progression to a higher tumor stage.

Highlights

Head and neck carcinomas are a group of malignant tumors originating form the upper aerodigestive tract including the oral cavity, pharynx, and larynx
Attempts to define the associations of p53 codon 72 polymorphism with cancer susceptibility or progression have yielded inconsistent results in different ethnic backgrounds and different types of cancer, including head and neck squamous cell carcinoma (HNSCC) . 6-11 Because there are no existing data for Iranian patients with HNSCC, we investigated the association between HNSCC susceptibility and p53 codon 72 polymorphism in a case-control study
Genotype frequencies did not differ significantly from those expected according to the Hardy-Weinberg equilibrium in patients or control participants

Summary

Introduction

Head and neck carcinomas are a group of malignant tumors originating form the upper aerodigestive tract including the oral cavity, pharynx, and larynx. More than 90% of head and neck carcinomas are squamous cell carcinoma, and arise from the epithelial tissues of these regions[1]. The incidence of head and neck squamous cell carcinoma (HNSCC) shows a wide range of geographical variation, with 500 000 new cases worldwide, and is more frequent in developing countries. The tumor suppressor p53 is a sequence-specific DNA-binding transcription factor that acts as the major cellular gatekeeper for growth and division. Normal cells express a low concentration of this nuclear protein in an inactive form, but in response to a wide variety of cellular stresses such as DNA damage, hypoxia, or the depletion of ribonucleoside triphosphate pools, p53 is activated and overexpressed. P53 mediates either 1) cell cycle arrest to allow DNA repair, or 2) apoptosis to remove the irreparably damaged cells[3]

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