Downregulation of ATM and BRCA1 Predicts Poor Outcome in Head and Neck Cancer: Implications for ATM-Targeted Therapy.

and are DNA repair genes that play a central role in homologous recombination repair. Alterations of and gene expression are found in cancers, some of which are correlated with treatment response and patient outcome. However, the role of and gene expression in head and neck cancer (HNC) is not well characterized. Here, we examined the prognostic role of and expression in two HNC cohorts with and without betel quid (BQ) exposure. The results showed that the expression of and was downregulated in BQ-associated HNC, as the BQ ingredient arecoline could suppress the expression of both genes. Low expression of either or was correlated with poor overall survival (OS) and was an independent prognostic factor in multivariate analysis ( HR: 1.895, = 0.041; HR: 2.163, = 0.040). The combination of and expression states further improved on the prediction of OS (HR: 4.195, = 0.001, both low vs. both high expression). Transcriptomic analysis showed that inhibition of ATM kinase by KU55933 induced apoptosis signaling and potentiated cisplatin-induced cytotoxicity. These data unveil poor prognosis in the HNC patient subgroup with low expression of and and support the notion of -targeted therapy.