Oncotarget

Research Papers:

Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention

Gwendolyn J. McGinnis, Sarah Holden, Betty Yu, Charlton Ransom, Carolyn Guidarelli, Brian De, Kevin Diao, David Boyce, Charles R. Thomas Jr., Kerri Winters-Stone and Jacob Raber _

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Oncotarget. 2022; 13:1259-1270. https://doi.org/10.18632/oncotarget.28310

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Abstract

Gwendolyn J. McGinnis1, Sarah Holden2, Betty Yu2, Charlton Ransom2, Carolyn Guidarelli3, Brian De1, Kevin Diao1, David Boyce1, Charles R. Thomas Jr.4,5, Kerri Winters-Stone3,6,* and Jacob Raber2,4,7,*

1 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

2 Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA

3 School of Nursing, Oregon Health and Science University, Portland, OR 97239, USA

4 Department of Radiation Medicine, Oregon Health and Science University, Portland, OR 97239, USA

5 Department of Radiation Oncology, Dartmouth-Hitchcock’s Dartmouth Cancer Center, Lebanon, NH 03756, USA

6 Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA

7 Department of Neurology and Division of Neuroscience, ONPRC, Oregon Health and Science University, Portland, OR 97239, USA

* Joint last authors

Correspondence to:

Jacob Raber, email: [email protected]

Keywords: apoE; breast cancer; exercise intervention; fall rate; functional status

Received: October 07, 2022     Accepted: October 31, 2022     Published: November 17, 2022

Copyright: © 2022 McGinnis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Purpose/Objectives: Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer. We tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention.

Materials and Methods: Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50–75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments.

Results: Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not.

Conclusions: APOE genotype may modulate cancer treatment related side effects and symptoms and response to exercise intervention.


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