Molecular Characterization ofTP53Gene in Human Populations Exposed to Low-Dose Ionizing Radiation

Abstract

Ionizing radiation, such as that emitted by uranium, may cause mutations and consequently lead to neoplasia in human cells. TheTP53gene acts to maintain genomic integrity and constitutes an important biomarker of susceptibility. The present study investigated the main alterations observed in exons 4, 5, 6, 7, and 8 of theTP53gene and adjacent introns in Amazonian populations exposed to radioactivity. Samples were collected from 163 individuals. Occurrence of the following alterations was observed: (i) a missense exchange in exon 4 (Arg72Pro); (ii) 2 synonymous exchanges, 1 in exon 5 (His179His), and another in exon 6 (Arg213Arg); (iii) 4 intronic exchanges, 3 in intron 7 (C → T at position 13.436; C → T at position 13.491; T → G at position 13.511) and 1 in intron 8 (T → G at position 13.958). Alteration of codon 72 was found to be an important risk factor for cancer development (P=0.024;OR=6.48; CI: 1.29–32.64) when adjusted for age and smoking. Thus,TP53gene may be an important biomarker for carcinogenesis susceptibility in human populations exposed to ionizing radiation.