Genetic variants and cognitive functions in patients with brain tumors

Author:

Correa Denise D12,Satagopan Jaya3,Martin Axel3,Braun Erica1,Kryza-Lacombe Maria4,Cheung Kenneth3,Sharma Ajay3,Dimitriadoy Sofia3,O’Connell Kelli3,Leong Siok3,Karimi Sasan1,Lyo John1,DeAngelis Lisa M12,Orlow Irene3

Affiliation:

1. Department of Neurology and Radiology, Memorial Sloan Kettering Cancer Center, New York, New York

2. Department of Neurology, Weill Cornell Medical College, New York, New York

3. Department of Epidemiology and Biostatistics and Radiology, Memorial Sloan Kettering Cancer Center, New York, New York

4. San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, California

Abstract

AbstractBackgroundPatients 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.MethodsOne 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: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable 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 (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis 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.

Funder

Society of MSK

National Cancer Institute

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Clinical Neurology,Oncology

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