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. 2019 Oct 9;21(10):1297-1309.
doi: 10.1093/neuonc/noz094.

Genetic variants and cognitive functions in patients with brain tumors

Denise D Correa  1   2 , Jaya Satagopan  3 , Axel Martin  3 , Erica Braun  1 , Maria Kryza-Lacombe  4 , Kenneth Cheung  3 , Ajay Sharma  3 , Sofia Dimitriadoy  3 , Kelli O'Connell  3 , Siok Leong  3 , Sasan Karimi  1 , John Lyo  1 , Lisa M DeAngelis  1   2 , Irene Orlow  3
Affiliations

Genetic variants and cognitive functions in patients with brain tumors

Denise D Correa et al. Neuro Oncol. .

Abstract

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: (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.

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 (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.

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.

Keywords: SNP; brain tumors; cognitive; genes; polymorphisms.

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References

    1. Meyers CA, Brown PD. Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors. J Clin Oncol. 2006;24(8):1305–1309. - PubMed
    1. Orr N, Chanock S. Common genetic variation and human disease. Adv Genet. 2008;62:1–32. - PubMed
    1. Wefel JS, Noll KR, Scheurer ME. Neurocognitive functioning and genetic variation in patients with primary brain tumours. Lancet Oncol. 2016;17(3):e97–e108. - PMC - PubMed
    1. Correa DD, Satagopan J, Baser RE, et al. . APOE polymorphisms and cognitive functions in patients with brain tumors. Neurology. 2014;83(4):320–327. - PMC - PubMed
    1. Correa DD, Satagopan J, Cheung K, et al. . COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors. Neuro Oncol. 2016;18(10):1425–1433. - PMC - PubMed

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