ATM, BCL2, and TGFβ Gene Polymorphisms as Radiotherapy Outcome Biomarkers in Head and Neck Squamous Cell Carcinoma Patients.

Autor:	Agostini LP; 1 Department of Cell Biology, Universidade Federal do Espírito Santo , Vitória, Brazil., Stur E; 1 Department of Cell Biology, Universidade Federal do Espírito Santo , Vitória, Brazil., Garcia FM; 1 Department of Cell Biology, Universidade Federal do Espírito Santo , Vitória, Brazil., Ventorim DP; 1 Department of Cell Biology, Universidade Federal do Espírito Santo , Vitória, Brazil., Dos Reis RS; 1 Department of Cell Biology, Universidade Federal do Espírito Santo , Vitória, Brazil., Dettogni RS; 1 Department of Cell Biology, Universidade Federal do Espírito Santo , Vitória, Brazil., Dos Santos EVW; 1 Department of Cell Biology, Universidade Federal do Espírito Santo , Vitória, Brazil., Peterle GT; 2 Department of Cell Biology, Universidade Federal do Espírito Santo , Alegre, Brazil., Maia LL; 2 Department of Cell Biology, Universidade Federal do Espírito Santo , Alegre, Brazil., Mendes SO; 2 Department of Cell Biology, Universidade Federal do Espírito Santo , Alegre, Brazil., de Carvalho MB; 3 Hospital Heliópolis , Nova Heliópolis, Brazil., Tajara EH; 4 Faculdade de Medicina de São José do Rio Preto , São José do Rio Preto, Brazil., de Paula F; 1 Department of Cell Biology, Universidade Federal do Espírito Santo , Vitória, Brazil., Dos Santos M; 5 Department of Cell Biology, Universidade Federal do Rio Grande do Norte , Caicó, Brazil., da Silva AMA; 2 Department of Cell Biology, Universidade Federal do Espírito Santo , Alegre, Brazil., Louro ID; 1 Department of Cell Biology, Universidade Federal do Espírito Santo , Vitória, Brazil.
Jazyk:	angličtina
Zdroj:	Genetic testing and molecular biomarkers [Genet Test Mol Biomarkers] 2017 Dec; Vol. 21 (12), pp. 727-735. Date of Electronic Publication: 2017 Nov 14.
DOI:	10.1089/gtmb.2017.0180
Abstrakt:	Aims: Polymorphisms in cell cycle genes are considered prognostic as radiosensitivity markers in patients with head and neck squamous cell carcinoma. Therefore, we aimed to investigate the relationship of ATM 5557G>A, ATM IVS62 + 60G>A, TP53 215G>C, BCL2-938C>A, TGFβ-509C>T, and TGFβ 29C>T with radiotherapy response. Materials and Methods: Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism in 210 patients with oral cavity/oropharyngeal carcinoma and 101 patients with laryngeal tumors. Results: In irradiated oral cavity/oropharyngeal tumors, the ATM IVS62 + 60G>A AA genotype significantly increased local recurrence risk (odds ratio [OR] = 4.43; confidence interval [CI] = 1.22-16.13) and the BCL2-938C>A C allele and the TGFβ-509C>T T allele were associated with worse disease-specific survival (hazard ratio [HR] = 0.46; CI = 0.24-0.90 and HR = 2.20; CI = 1.12-4.29, respectively). In irradiated laryngeal carcinoma, the TGFβ 29C>T C allele was associated with increased local recurrence risk (OR = 0.09; CI = 0.02-0.53), death rate (OR = 0.18; CI = 0.04-0.86), and worse local disease-free and disease-specific survival rates (HR = 0.13; CI = 0.03-0.59 and HR = 0.21; CI = 0.07-0.60, respectively), while the BCL2-938C>A C allele was related to a worse disease-specific survival (HR = 0.32; CI = 0.12-0.83). Discussion: These results can help individualize treatment according to a patient's genetic markers. We demonstrated that ATM IVS62 + 60G>A, TGFβ 29C>T, TGFβ-509C>T, and BCL2-938C>A can function as biomarkers of tumor radiosensitivity, being candidates for a predictive genetic profile of radiotherapy response.
Databáze:	MEDLINE
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