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Abstract
BACKGROUND: Cognitive dysfunction is prevalen among brain tumor patients treated with radiotherapy (RT) and chemotherapy (CT). However, little is known about genetic risk factors that may moderate their vulnerability for developing cognitive impairment. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in three genes, Catechol-O-Methyl-Transferase (COMT), Brain-Derived-Neurotrophic-Factor (BDNF), and dystrobrevin binding protein 1 (DTNBP1), and cognitive functions in brain tumor survivors. METHODS: One hundred and fifty brain tumor patients participated in the study: ninety had been treated with RT ± CT, fifty-seven had CT alone, and three had no therapy. All Patients completed a battery of neuropsychological tests of attention, executive functions and memory, and provided a blood sample. Genotyping of SNPs in the BDNF (n = 9), COMT (n = 17) and DTNBP1 (n = 7) genes was performed. RESULTS: Linear regressions with stepwise backward elimination of SNPs based on change in AIC criterion, adjusting for age, education, and treatment type indicated a significant (p< 0.05) association between the COMT SNP rs4680 (Val158Met) and cognitive function, with lower working memory scores in homozygotes (G/G) and higher executive function and delayed recall scores in heterozygotes (A/G). Five additional SNPs in the COMT gene were significantly associated with lower scores in attention and executive functions. There were significant associations among five SNPs in the BDNF gene and lower performance in executive function, learning and delayed recall. Four SNPs in the DTNBP1 gene were associated with attention and memory scores. CONCLUSION: The findings suggest that in brain tumor patients, cognitive outcome may be differentially affected by polymorphisms in genes previously associated with executive and memory functions in healthy individuals and other clinical populations. Further work is underway to quantify the variation in cognitive outcomes explained by these polymorphisms.
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