The impact of APOE and smoking history on cognitive function in older, long-term breast cancer survivors Journal Article


Authors: Ahles, T. A.; Orlow, I.; Schofield, E.; Li, Y.; Ryan, E.; Root, J. C.; Patel, S. K.; McNeal, K.; Gaynor, A.; Tan, H.; Katheria, V.; Vazquez, J.; Corrales–Guerrero, S.; Sadeghi, K.; Traina, T.; Hurria, A.
Article Title: The impact of APOE and smoking history on cognitive function in older, long-term breast cancer survivors
Abstract: Purpose: This study aims to determine whether older breast cancer survivors score lower on neuropsychological tests compared to matched non-cancer controls and to test the hypotheses that survivors who were APOE ε4 carriers would have the lowest cognitive performance but that smoking history would decrease the negative effect of ε4 on cognition. Methods: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5–15-year survivors (N = 328) and age and education matched non-cancer controls (N = 162) were assessed at enrollment and at 8-, 16-, and 24-month follow-ups with standard neuropsychological and psychological assessments. Blood for APOE genotyping was collected, and smoking history was assessed at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or no chemotherapy and approximately 50% had a smoking history. Results: After adjusting for age, cognitive reserve, depression, and fatigue, breast cancer survivors scored significantly lower on all domains of cognitive function. A significant two-way interaction demonstrated that the negative effect of ε4 on cognitive performance was stronger among survivors. A significant three-way interaction supported the hypothesis that smoking history had a protective effect on cognitive function in ε4 carriers that was more pronounced in the controls than the survivors. Conclusions: The results support the long-term cognitive impact of breast cancer diagnosis and treatments on older, disease-free survivors, particularly for ε4 carriers. The results also emphasize the importance of assessing smoking history when examining APOE and cognition and are an example of the complex interactions of age, genetics, health behaviors, and disease history in determining cognitive function. Implications for Cancer Survivors: These results help explain why only a subset of breast cancer survivors appear to be vulnerable to cognitive problems. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.
Keywords: smoking; cognition; apoe; older breast cancer survivor
Journal Title: Journal of Cancer Survivorship
Volume: 18
Issue: 2
ISSN: 1932-2259
Publisher: Springer  
Date Published: 2024-04-01
Start Page: 575
End Page: 585
Language: English
DOI: 10.1007/s11764-022-01267-z
PUBMED: 36279076
PROVIDER: scopus
PMCID: PMC10123173
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Tim A. Ahles -- Source: Scopus
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MSK Authors
  1. Yuelin Li
    219 Li
  2. Tim A Ahles
    182 Ahles
  3. Elizabeth Ryan
    20 Ryan
  4. James Charles Root
    113 Root
  5. Irene Orlow
    247 Orlow
  6. Tiffany A Traina
    250 Traina
  7. Elizabeth A Schofield
    158 Schofield
  8. Alexandra Gaynor
    9 Gaynor
  9. Katrazyna J Mcneal
    4 Mcneal