Avaliação de polimorfismos dos genes ATM, TP53, BCL2 e TGFb relacionados com o prognóstico de pacientes com carcinoma epidermóide de cabeça e pescoço : relação com radiossensibilidade tumoral
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Data
2014-02-26
Autores
Agostini, Lidiane Pignaton
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Universidade Federal do Espírito Santo
Resumo
Polymorphisms in genes that control DNA repair, cell cycle, apoptosis and cytokine transcription, are pointed as putative prognosis and radiosensibility markers in Head and Neck Squamous Cell Carcinoma (HNSCC) patients. We have typed polymorphisms ATM IVS62+60G>A, ATM Asp1853Asn, TP53 Arg72Pro, BCL2 - 938C>A, TGFβ Pro10Leu and TGFβ -509C>T in order to establish correlations with prognosis and treatment response in HNSCC patients, using the PCR-RFLP technique. Genotyping was performed using peripheral blood DNA from 210 patients with oral and oropharyngeal tumors and 101 patients with larynx tumors. In patients with oral and oropharyngeal tumors submitted to radiotherapy tretament, genotype ATM IVS62+60AA increases local relapse risk (OR=4.43; CI=1.22-16.13) and alleles BCL2 -938C and TGFβ -509T are related with worse disease-specific survival (HR=0.46; CI=0.24-0.90 e HR=2.20; CI=1.12-4.29, respectively). In contrast, patients not submitted to radioation therapy, homozygous TP53 Pro72 increases risk of death (OR=2.65; CI=1.05-6.65). In irradiated larynx tumor patients, allele TGFβ Pro10 was associated with local relapse risk (OR=0.09; CI=0.02-0.53) and death (OR=0.18; CI=0.04-0.86), as well as with worse local disease-free survival and disease-specific survival (HR=0.13; CI=0.03-0.59 and HR=0.21; CI=0.07-0.60, respectively). Allele BCL2 -938C was associated with worse disease specific survival (HR=0.32; CI=0.12- 0.83). TGFβ -509T was associated with higher risk of death in non-irradiated larynx patients (OR=9.11; CI=1.51-27.91). Therefore, we suggest these polymorphisms as markers of prognosis and radiosensibility in these tumors.
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Head and neck squamous cell carcinoma , Radiosensitivity , Prognosis , Polymorphisms , Carcinoma epidermóide de cabeça e pescoço , Radiossensibilidade , Polimorfismos