The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy

Purpose: The primary purpose of this study was to compare the neuropsychological performance of long-term survivors of breast cancer and lymphoma treated with standard dose chemotherapy who carried the epsilon4 allele of the Apolipoprotein E (APOE) gene to those who carry other APOE alleles. Patients and methods: Long-term survivors (mean = 8.8 +/- 4.3 years post-treatment) of breast cancer (N = 51, age = 55.9 +/- 8.8) or lymphoma (N = 29, age = 55.8 +/- 11.6) who had been treated with standard-dose chemotherapy completed a standaraized battery of neuropsychological and psychological tests. Survivors were also classified into two groups based on the presence (N = 17) or absence (N = 63) of at least one epsilon4 allele of APOE. Results: Analysis of covariance, controlling for age, gender, education, diagnosis, and WRAT-3 reading subtest (a proxy measure of baseline IQ). indicated that survivors with at least one epsilon4 allele scored significantly lower in the visual memory (p<0.03) and the spatial ability (p<0.05) domains and tended to score lower in the psychomotor functioning (p<0.08) domain as compared to survivors who did not carry an epsilon4 allele. No group differences were found on depression, anxiety, or fatigue. Conclusions: The results of this study provide preliminary support for the hypothesis that the epsilon4 allele of APOE may be a potential genetic marker for increased vulnerability to chemotherapy-induced cognitive decline. Copyright (C) 2003 John Wiley Sons, Ltd.