ABSTRACT: Abstract BACKGROUND Cognitive dysfunction is common in patients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT). We reported previously that single nucleotide polymorphisms (SNPs) in the APOE, COMT and BDNF genes may influence cognitive outcome in this clinical population. In this study, we assessed whether additional genes with known associations with aging, Alzheimer’s disease and inflammation may contribute to cognitive dysfunction in brain tumor survivors. METHODS One hundred and fifty patients with brain tumors participated in the study: ninety had been treated with RT ± CT, fifty-seven had CT alone, and three had no therapy. All patients completed neuropsychological tests of attention, executive functions and memory, and provided a blood sample for genotyping. We used a Bayesian penalized multivariate regression approach to estimate the associations between the SNPs and cognitive outcome, adjusting for age, education, tumor location, treatment with RT ± CT, time since treatment completion, and APOE epsilon ?-4 allele. We quantified the strength of association between a SNP and a cognitive test score using a novel measure referred to as the posterior association summary (PAS) that takes value between 0 (= no association) and 1 (= very strong association). RESULTS Several SNPs previously reported in association with age-related cognitive decline and Alzheimer’s disease (PDE7A rs10808746, CD2AP rs9349407, ABCC1 rs8187858, APOE rs405697) and inflammation (IL-1A rs1800587, IL-1 rs1143634, IL-6 rs1474348) were strongly associated with tests of attention, executive functions and memory (PAS ? 0.95). Several additional SNPs that mapped to the ABCA7, CD33, COMT, IL-6, MS4A4E, PDE7A, PICALM, SERPINA3 and SORC1 genes were also associated with tests of attention and executive functions with PAS ? 0.90. CONCLUSION The findings provide new evidence that polymorphisms in genes associated with aging, Alzheimer’s disease and inflammation may be functionally relevant and influence cognitive outcome in patients with brain tumors.
