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

Abstract 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 ε4 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 standardized 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 ε4 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 ε4 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 ε4 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 ε4 allele of APOE may be a potential genetic marker for increased vulnerability to chemotherapy‐induced cognitive decline. Copyright © 2003 John Wiley & Sons, Ltd.