title: Molecular characterization of TP53 gene 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. The TP53 gene 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 the TP53 gene 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, TP53 gene may be an important biomarker for carcinogenesis susceptibility in human populations exposed to ionizing radiation.
authors.affiliation: Laboratory of Human and Medical Genetics, Biological Sciences Institute, Federal University of Pará (UFPA), Augusto Correa Street, Number 01, CEP 66075-110 Belém, PA, Brazil.
authors.forename: Igor
authors.initials: I
authors.lastname: Brasil-Costa
authors.forename: Dayse O
authors.initials: DO
authors.lastname: Alencar
authors.forename: Milene
authors.initials: M
authors.lastname: Raiol-Moraes
authors.forename: Igor A
authors.initials: IA
authors.lastname: Pessoa
authors.forename: Alexandre W M
authors.initials: AW
authors.lastname: Brito
authors.forename: Schneyder R
authors.initials: SR
authors.lastname: Jati
authors.forename: Sidney E B
authors.initials: SE
authors.lastname: Santos
authors.forename: Rommel M R
authors.initials: RM
authors.lastname: Burbano
authors.forename: Andrea K C
authors.initials: AK
authors.lastname: Ribeiro-dos-Santos
mesh_terms: D000328:Adult; D000483:Alleles; D002471:Cell Transformation, Neoplastic; D004781:Environmental Exposure; D005091:Exons / Q000528:radiation effects*; D042822:Genomic Instability / Q000528:radiation effects*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D014501:Uranium / Q000633:toxicity
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014501:Uranium