Apolipoprotein ε4-allele as predictor of outcome in radiotherapy-treated childhood brain tumor survivors

Abstract Background Apolipoprotein E (APOE) is a polymorphic gene with three main alleles; the ε4-allele is a risk factor for distinct diseases, particularly for Alzheimer’s disease. Radiotherapy-treated childhood brain tumor (BT) survivors face an increased risk of developing late-effects, especially cognitive impairment. Despite the similar treatment modality, the outcome varies considerably. Thus, we investigated the influence of ε4-allele on outcome in these survivors. Methods A Finnish national cohort of radiotherapy-treated childhood BT survivors was investigated in a cross-sectional setting (median follow-up of 20 years). Survivors participated in the follow-up visit including neuropsychological and physical examinations, brain magnetic resonance imaging, and laboratory tests. BT and treatment-related information were collected from the patient files. APOE polymorphism was examined, and the results were compared to a previous study on the Finnish population. We also compared the late-effects between ε4-carriers and non-carriers. Results Among 58 survivors [median age of 27 (range, 16-43) years], the observed frequencies of APOE genotypes were 78% (N = 45) for ε3ε3, 14% (N = 8) for ε3ε4, 7% (N = 4) for ε2ε3, and 2% (N = 1) for ε2ε4. The presence of ε4-allele was associated with poorer semantic, immediate, and delayed auditory memory. Since all ε4-carriers had ventriculoperitoneal shunt, we compared their results to those of non-carriers with ventriculoperitoneal shunt, which revealed that ε4-carriers had worse immediate and delayed auditory memory. E4-carriers exhibit higher total cholesterol and triglyceride levels than non-carriers. Conclusions APOE ε4-allele may impact the cognitive outcome and cholesterol levels in the radiotherapy-treated childhood BT survivors. E4-carrier survivors may especially benefit from healthy life-style interventions.