COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors.
Cognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in the catechol-O-methyl transferase (COMT), brain-derived neurotrophic factor (BDNF), and dystrobrevin-binding protein 1 (DTNBP1) genes with cognitive functions and neuroimaging outcomes in patients with brain tumors.



One hundred and fifty patients with brain tumors completed neuropsychological tests of attention, executive functions, and memory and were genotyped for polymorphisms in the COMT, BDNF, and DTNBP1 genes. Ratings of white matter (WM) abnormalities on magnetic resonance imaging scans were performed.



Multivariate regression shrinkage analyses, adjusted for age, education, treatment type, time since treatment completion, and tumor location, indicated a significant association between the COMT SNP rs4680 (Val158Met) and memory with lower scores in delayed recall (P < .01) among homozygotes (valine/valine). Additional COMT, BDNF and DTNBP1 SNPs were significantly associated with attention, executive functions, and memory scores.



This is the first study to suggest that known and newly described polymorphisms in genes associated with executive and memory functions in healthy individuals and other clinical populations may modulate cognitive outcome in patients with brain tumors.
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.) corread@mskcc.org.
Denise D
DD
Correa
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.).
Jaya
J
Satagopan
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.).
Kenneth
K
Cheung
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.).
Arshi K
AK
Arora
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.).
Maria
M
Kryza-Lacombe
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.).
Youming
Y
Xu
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.).
Sasan
S
Karimi
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.).
John
J
Lyo
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.).
Lisa M
LM
DeAngelis
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (D.D.C., M.K.-L., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (J.S., K.C., A.K.A., Y.X., I.O.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (S.K., J.L.); Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York (D.D.C., L.M.D.).
Irene
I
Orlow
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; C579455:BDNF protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
BDNF; COMT; DTNBP1; brain tumors, cognitive