Reduced Expression of Atm Gene in Head and Neck Cancer

Abstract

ABSTRACT Aim: Lower ATM (ataxia telangiectasia mutated) gene expression is hypothesized to be a risk factor in head and neck cancer. The aim of the study was to determine the ATM gene expression in relation to clinical and histological parameters of the patients. Methods: Study group comprised of 63 patients with head and neck cancer, histologically diagnosed as squamous cell carcinoma. Mean age of patients was 63 (range 41-83), sex: 58 men and 4 women, with time of diagnosis from March 2012 to March 2014. Tumor location was: 76% larynx, 35% pharynx, 17,5% tongue, 19% metastases in cervical lymph nodes. Patients were characterized according to: histological grading, presence of metastases, method of treatment, smoking, alcohol drinking. Median of follow-up of patients was 12 months (range 1-25 months). Fresh tumor tissue and adjacent normal samples were used for extraction of RNA. The analysis based on RT-qPCR was performed on 7900HT Fast Real-Time PCR System (Applied Biosystems), using TaqMan assays. Expression level of ATM mRNA was calculated by 2-ΔΔCT method, in relation to GAPDH gene expression as internal control. Statistical analyses were performed using STATISTICA10 program (Statsoft Inc.), relationships were examined by chi2 square or Fisher exact test. Survival analyses were determined using Kaplan-Meier method and long-rank test. Results: Lower ATM gene expression was identified in 31,7% (20/63) of studied patients. Tumor location of the patients with lower ATM gene expression included: 60% laryngeal site (12 patients), 25% pharyngeal site (5 patients), 25% (5 patients) metastasis to cervical lymph nodes. Decreased ATM mRNA level was statistically correlated with shorter overall survival (p = 0.002). Smoking was more pronounced in the lower ATM expression group, but did not reach statistical significance (p= 0.079). As for other clinical and histological parameters, no statistically significant associations were shown. Conclusions: Our data suggest that ATM mRNA expression is a prognostic factor in head and neck cancer and is associated with worse outcome. Additionally, it seems probable that smoking can increase the risk of head and neck cancer by lowering the ATM gene expression, but the data should be confirmed. Disclosure: All authors have declared no conflicts of interest.