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.