Protective Effects of APOE epsilon2 Genotype on Cognition in Older Breast Cancer Survivors: The Thinking and Living with Cancer Study
Menée à partir de données portant sur 407 témoins et 427 patientes ayant survécu à un cancer du sein non métastatique et âgées de 60 à 98 ans, cette étude analyse les effets du polymorphisme epsilon
Background : Cancer-related cognitive decline (CRCD) has been linked to apolipoprotein E (APOE) gene
ε4 polymorphisms. APOE ε4 polymorphisms are also the strongest genetic risk for late-onset Alzheimer’s disease (AD), while ε2 polymorphisms protect against AD. However, the effects of ε2 polymorphisms on CRCD have not been evaluated. Methods
:
We evaluated non-metastatic breast cancer survivors (n
= 427) and matched non-cancer controls (n = 407) ages 60–98 assessed pre-systemic therapy/enrollment from August 2010-December 2017 with annual follow-up to 24 months. Neuropsychological assessment measured attention, processing speed, and executive function, and learning and memory. Linear mixed-effects models tested the effects of having an
ε2 allele (vs. none) on longitudinal cognitive domain z-scores by treatment group (chemotherapy +/- hormonal therapy, hormonal therapy, and control) controlling for covariates; participants with ε2/ε4 genotype were excluded. Sensitivity analyses examined effects of other covariates and any ε4 positivity. Results
:
There was an interaction with genotype for attention, processing speed, and executive functioning domain scores (Beta
= 0.32 (95% CI : 0.00, 0.65)): the chemotherapy group with an
ε2 allele had higher scores at baseline and maintained higher scores over time compared to those without an ε2 allele, and this protective effect was not seen for other groups. There was no effect of ε2 on learning and memory domain scores. Conclusions
:
APOE ε2 polymorphisms may protect against CRCD in older breast cancer survivors receiving chemotherapy. With replication, this information could be useful for survivorship care and informing future studies of possible links to AD and defining mechanisms of protection.
JNCI Cancer Spectrum 2021