P53 Codon 72 Gene Polymorphism and Risk of Oral Squamous Cell Carcinoma in South Indian Population: A Case-Control Study

Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms worldwide. Oral cancer forms a large part of the cancer load in the part of India [1]. Smoking, alcohol, drinking, viral infection and genetic factors are the major risk factors involved in the etiology of oral squamous cell carcinoma. Some molecular studies have provided some clues to the molecular mechanisms underlying such genetic susceptibility, and it is likely that they are genetically determined. DNA repair capacity may contribute to interindividual variation in susceptibility to head and neck carcinogenesis. The tumour suppressor gene p53 is crucial for host defence against genomic mutations which might cause many types of tumours. The p53 protein has pleiotropic functions in the modulation of genomic stability of cells. Disruption of p53 activity is commonly found in human cancers. The production of p53 is increased in response to cellular insults or DNA damage, and p53 then induces cell cycle arrest at the G1/S junction. If the damage is irreparable, p53 can initiate cell death by apoptosis [2]. Mutant proteins are defective in DNA binding in a sequence-specific manner, and thus in the upregulation of downstream genes [3]. So far 13 polymorphisms have been described in this gene [4]. The most commonly studied one is a single nucleotide polymorphism (SNP) at codon 72 in exon four of the p53 gene, which results in the substitution of arginine (Arg) by proline (Pro) in the transactivating domain. These two polymorphic variants (Pro72 and Arg72) alter the structure and function of the p53 protein [5]. The potential consequence of this amino acid exchange is differences in the susceptibility to malignant transformation, induction of apoptosis, and transcriptional activity [6]. The arginine (Arg72) allele increases the ability of p53 to locate to mitochondria and induce cellular death, whereas proline allele (Pro72) exhibits a lower apoptotic potential and an increased cellular arrest in G1 of the cell cycle [7]. Several epidemiological surveys reported association and non association of this codon 72 (Arg/Pro) polymorphism with different types of cancers [8], it suggests that Pro72 Pro genotype may be the potential risk factor favoring the development of lung carcinoma in Kerala population and Arg72Pro genotype is independently associated with a poorer prognosis of lung cancer. De Chaudhuri, et al. [9], in a study reported that individuals carrying the arginine homozygous genotype at codon 72 and no duplication homozygous genotype at intron three are at risk for the development of arsenic induced keratosis. Rajkumar et al. [10], study reported that SNP’s can help predict breast cancer risk in south Indian women. Sailaja et al. [11], suggests that proline genotype might confer increased risk to develop CML in Hyderabad population and is also associated with poor cytogenetic response. In Mumbai population equidistribution of the genotypes were detected in both normal controls and oral cancer patients. Thus Tandle et al. [12], in a study reported that Association of p53 genotypes with oral cancer was not detected. In contrast, to above investigations investigators in some studies demonstrated the non association between the different p53 polymorphisms and individual cancer development, other studies revealed the higher risks in the individuals with p53*Pro72 homozygote. The aim of the present study is to identify whether TP53 codon 72 polymorphism can be considered