Protective Effects of
| Autor: | Brenna C. McDonald, James C. Root, Jeanne S. Mandelblatt, Brent J. Small, Judith E. Carroll, Xingtao Zhou, Jaeil Ahn, Kathleen Van Dyk, Sunita K. Patel, Andrew J. Saykin, Harvey J. Cohen, G. William Rebeck, Deena Graham, Tim A. Ahles, Kelly N. Holohan, Wanting Zhai, Heather S.L. Jim, Paul B. Jacobsen |
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| Rok vydání: | 2020 |
| Předmět: |
Apolipoprotein E
Oncology Cancer Research medicine.medical_specialty Genotype Apolipoprotein E2 Apolipoprotein E4 Breast Neoplasms Neuropsychological Tests Article 03 medical and health sciences Executive Function 0302 clinical medicine Breast cancer Cognition Cancer Survivors Alzheimer Disease Memory Internal medicine medicine Humans Learning Attention Cognitive Dysfunction Neuropsychological assessment Cognitive decline Aged Aged 80 and over Polymorphism Genetic medicine.diagnostic_test business.industry Cancer Middle Aged medicine.disease Chemotherapy regimen 030220 oncology & carcinogenesis Case-Control Studies Hormonal therapy Female Alzheimer's disease AcademicSubjects/MED00010 business 030217 neurology & neurosurgery |
| Zdroj: | JNCI Cancer Spectrum |
| ISSN: | 2515-5091 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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