Genetic Variants and Cognitive Functions in Patients with Brain Tumors.

BACKGROUND Patients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer's disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population. METHODS One hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: 1) LOAD risk/inflammation/cholesterol transport; (2) dopamine-regulation; (3) myelin-regulation; (4) DNA-repair; (5) blood-brain-barrier- disruption, (6) cell- cycle-regulation, and (7) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs. RESULTS Multivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease and treatment variables, indicated strong associations (Posterior Association Summary, PAS ≥ 0.95) among tests of attention, executive functions and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (e.g., PDE7A, IL-6), dopamine-regulation (e.g., DRD1, COMT), myelin-repair (e.g., TCF4), DNA-repair (e.g., RAD51), cell-cycle-regulation (e.g., SESN1), and response to oxidative stress (e.g., GSTP1). The SNPs were not significantly associated with WM abnormalities. CONCLUSION This novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress, may be associated with cognitive outcome in patients with brain tumors.