Abstract 1558: TP53 codon 72 polymorphism association with prognosis in Puerto Rican head and neck squamous cell carcinoma patients

Abstract

Abstract Objective: The p53 gene has many polymorphic sites that result in an altered activity of the protein, which may be associated to cancer risk. The polymorphic site of p53 at exon 4 codon 72 is a base substitution that produces an Arginine or a Proline (Arg72Pro). Each amino acid gives a specific function to p53, which may be associated to cancer susceptibility. This polymorphism is differentially dispersed among different ethnic populations. It has been widely studied in cancer, but still, epidemiologic findings relating p53 polymorphism and cancer risk have been inconsistent. The objective of this study was to evaluate the effect(s) of p53 polymorphism at exon 4 codon 72 on the prognosis of head and neck squamous cell carcinoma (HNSCC) in the Puerto Rican population. Methods: p53 polymorphism Arg72Pro, (rs1042522), was determined in a cohort of 131 HNSCC patients and 45 healthy controls. Genotyping of p53 polymorphism was accomplished using PCR-based restriction fragment polymorphism (PCR-RFLP). Associations between clinicopathological parameters and p53 polymorphism were analyzed by Fisher's exact test and chi-square when suitable. Survival analysis of HNSCC patients, with each type of p53 genotype, was performed using Kaplan-Meier test. Results: The frequencies for homozygote Arg allele were 38.1% in HNSCC cases and 31.1% in healthy controls. The Pro allele carriers (Arg/Pro plus Pro/Pro) had a frequency of 61.9% in HNSCC cases and 68.9% in healthy controls. The OR of HNSCC cancer-associated with the Arg/Arg genotypes of codon 72 was 1.37 [95% CI: 0.63-2.82]. Kaplan-Meier survival analysis showed that HNSCC patients with the Arg/Arg allele had a poorer survival rate compared to patients with the Pro allele (Hazard Ratio = 1.33, 95% CI: 0.87-2.03, P=0.041). Additionally, p53 genotype and survival of HNSCC patients, classified by tumor site, was evaluated, and showed that Arg/Arg allele had a poorer survival rate, specifically for the larynx site (Hazard Ratio = 1.88, 95% CI: 0.98-3.60, P=0.035). In contrast, no statistically significant association was found between p53 polymorphic variants and gender, age, risk factors and staging. Conclusion: Our results suggest that homozygosity for Arg of p53 Arg72Pro may have a role in the progression of HNSCC in the Puerto Rican population. Detection of the p53 polymorphic variants may be used as an indicator of prognosis in HNSCC patients. Accurate prognosis in HNSCC will help clinicians to establish proper treatment and increase the survival of HNSCC patients. Citation Format: Bianca L. Rivera, Ricardo López, Roger Vázquez, Yarilis Castro, Adriana Báez. TP53 codon 72 polymorphism association with prognosis in Puerto Rican head and neck squamous cell carcinoma patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1558. doi:10.1158/1538-7445.AM2014-1558