TP53 p.R72P genotype is a marker of poor prognosis in lung cancer.

Abstract

Lung cancer is a leading cause of death worldwide, with poor survival rates despite diagnostic and therapeutic advances. Markers are needed in order to improve clinical patient management and survival. TP53 is frequently involved in lung cancer development with polymorphic sites potentially having a role in it. This study aims to determine the value of codon 72 missense polymorphic variant genotyping, TP53 R72P, as a prognostic factor in NSCLC patients. One hundred and fifteen NSCLC samples from patients exposed to tobacco smoke and silica dust from Asturias (Northern Spain) were genotyped by direct sequencing. Seventy-five percent tumour samples alleles coded for Arg. The R72P genotype was an independent predictor of lymph node status (HR = 3.6). The heterozygous genotype was associated to a reduced 5-year survival rate (28% vs 51% for homozygotes). Importantly, this result was specifically observed in these subsets of patients: those over 67 years, patients with silicosis, current smokers, patients with squamous cell carcinomas and, notably, with tumour free lymph nodes. Our results indicate a remarkable application of R72P genotyping in the clinical setting: refine patient subclassification to identify those with an adverse clinical course despite tumour free lymph node status.