title: Investigation of genetic polymorphisms related to the outcome of radiotherapy for prostate cancer patients.
abstract: The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002-0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006-0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy.
authors: Programa de Mestrado em Genética, Pontifícia Universidade Católica de Goiás, Avenida Universitária 1440 Setor Universitário, 74605-010 Goiânia, GO, Brazil ; Laboratório de Oncogenética e Radiobiologia, Associação de Combate ao Câncer em Goiás, Rua 239 N.52 Lt.29, Setor Universitário, 74605-070 Goiânia, GO, Brazil.
authors: Hellen Silva
authors: HS
authors: Cintra
authors: Juliana Castro Dourado
authors: JC
authors: Pinezi
authors: Graziella Dias Pinheiro
authors: GD
authors: Machado
authors: Gustavo Moura
authors: GM
authors: de Carvalho
authors: Ana Terra Silva
authors: AT
authors: Carvalho
authors: Thalles Eduardo Dias
authors: TE
authors: dos Santos
authors: Ricardo Duarte
authors: RD
authors: Marciano
authors: Renata de Bastos Ascenço
authors: Rde B
authors: Soares
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D059248:Chemoradiotherapy; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D011832:Radiation Injuries / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D017422:Sequence Analysis, DNA; D012871:Skin Diseases / Q000235:genetics; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins