ATM, BCL2, and TGFb gene polymorphisms as radiotherapy outcome biomarkers in head and neck squamous cell carcinoma patients

• Main Author: Agostini, Lidiane Pignaton
• Publication Date: 2017
• Other Authors: Stur, Elaine, Garcia, Fernanda M., Ventorim, Diego P., Reis, Raquel S. dos, Dettogni, Raquel S., Santos, Eldamária V. W. dos, Peterle, Gabriela T., Maia, Lucas L., Mendes, Suzanny O., Carvalho, Marcos B. de, Tajara, Eloiza H., Paula, Flavia de, Santos, Marcelo dos, Silva, Adriana M. A. da, Louro, Iúri Drumond
• Format: Article
• Language: eng
• Source: Repositório Institucional da UFRN
• Download full: https://repositorio.ufrn.br/handle/123456789/31363
• topic: Head and neck squamous cell carcinoma; Oral cavity/oropharynx; Larynx; Radiosensitivity; Polymorphisms

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, TGFb-509C>T, and TGFb 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 TGFb-509C>T T allele were associated with worse disease-specific survival (hazar dratio [HR] = 0.46; CI = 0.24–0.90 and HR = 2.20; CI = 1.12–4.29, respectively). In irradiated laryngeal carcinoma, the TGFb 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, TGFb 29C>T, TGFb-509C>T, and BCL2-938C>A can function as biomarkers of tumor radiosensitivity, being candidates for a predictive genetic profile of radiotherapy response