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Protective Effects of APOE ε2 Genotype on Cognition in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study.

Publication ,  Journal Article
Van Dyk, K; Zhou, X; Small, BJ; Ahn, J; Zhai, W; Ahles, T; Graham, D; Jacobsen, PB; Jim, H; McDonald, BC; Nudelman Holohan, K; Patel, SK ...
Published in: JNCI Cancer Spectr
April 2021

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 disease (AD), whereas ε2 polymorphisms protect against AD. However, the effects of ε2 polymorphisms on CRCD have not been evaluated. METHODS: We evaluated nonmetastatic breast cancer survivors (n = 427) and matched noncancer controls (n = 407) ages 60-98 years assessed presystemic therapy from August 2010 to December 2017 with annual follow-up to 24 months. Neuropsychological assessment measured attention, processing speed, 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 with or without 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% confidence interval = 0.00 to 0.65); the chemotherapy group with an ε2 allele had higher scores at baseline and maintained higher scores over time compared with 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.

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Published In

JNCI Cancer Spectr

DOI

EISSN

2515-5091

Publication Date

April 2021

Volume

5

Issue

2

Location

England

Related Subject Headings

  • Polymorphism, Genetic
  • Neuropsychological Tests
  • Middle Aged
  • Memory
  • Learning
  • Humans
  • Genotype
  • Female
  • Executive Function
  • Cognitive Dysfunction
 

Citation

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Van Dyk, K., Zhou, X., Small, B. J., Ahn, J., Zhai, W., Ahles, T., … Carroll, J. E. (2021). Protective Effects of APOE ε2 Genotype on Cognition in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study. JNCI Cancer Spectr, 5(2). https://doi.org/10.1093/jncics/pkab013
Van Dyk, Kathleen, Xingtao Zhou, Brent J. Small, Jaeil Ahn, Wanting Zhai, Tim Ahles, Deena Graham, et al. “Protective Effects of APOE ε2 Genotype on Cognition in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study.JNCI Cancer Spectr 5, no. 2 (April 2021). https://doi.org/10.1093/jncics/pkab013.
Van Dyk K, Zhou X, Small BJ, Ahn J, Zhai W, Ahles T, et al. Protective Effects of APOE ε2 Genotype on Cognition in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study. JNCI Cancer Spectr. 2021 Apr;5(2).
Van Dyk, Kathleen, et al. “Protective Effects of APOE ε2 Genotype on Cognition in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study.JNCI Cancer Spectr, vol. 5, no. 2, Apr. 2021. Pubmed, doi:10.1093/jncics/pkab013.
Van Dyk K, Zhou X, Small BJ, Ahn J, Zhai W, Ahles T, Graham D, Jacobsen PB, Jim H, McDonald BC, Nudelman Holohan K, Patel SK, Rebeck GW, Root JC, Saykin AJ, Cohen HJ, Mandelblatt JS, Carroll JE. Protective Effects of APOE ε2 Genotype on Cognition in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study. JNCI Cancer Spectr. 2021 Apr;5(2).

Published In

JNCI Cancer Spectr

DOI

EISSN

2515-5091

Publication Date

April 2021

Volume

5

Issue

2

Location

England

Related Subject Headings

  • Polymorphism, Genetic
  • Neuropsychological Tests
  • Middle Aged
  • Memory
  • Learning
  • Humans
  • Genotype
  • Female
  • Executive Function
  • Cognitive Dysfunction