Currently submitted to: JMIR Research Protocols
Date Submitted: Sep 5, 2026
Open Peer Review Period: Sep 8, 2026 - Nov 3, 2026
(currently open for review)
Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Influence of Dietary Adversity on Fatigue, the Mammalian Target of Rapamycin (mTOR) Pathway and the Epigenome: Protocol for a Longitudinal Observational Cohort Study
ABSTRACT
Background:
Exposure to both radiation therapy to treat prostate cancer and dietary adversity (i.e., food insecurity and poor diet quality), which has increased owing to current financial instability, can each drive epigenetic reprogramming resulting in the dysregulation of biological pathways implicated in cancer-related fatigue. Yet, the extent to which dietary adversity, and other social determinants of health alter the epigenetic regulation of genes involved in the mammalian target of rapamycin (mTOR) pathway involved in autophagy to regulate cell growth and in energy homeostasis is unknown, as is their impact on post-treatment cancer-related fatigue. The team is conducting a study to address this knowledge gap.
Objective:
To describe an ongoing study protocol designed to determine the impact of social determinants of health and epigenetic dysregulation of mTOR-related host genes on post-treatment cancer-related fatigue
Methods:
This protocol utilizes a prospective longitudinal study design. Newly diagnosed men with prostate cancer scheduled to receive stereotactic body radiotherapy (SBRT) provide self-reported surveys on fatigue, food security, diet intake and other social determinants of health, and blood samples to evaluate DNA methylation of mTOR-related genes. Phenotypic data are collected at three time points (before SBRT and at 1 and 6 months after SBRT), while biospecimens are collected before treatment, with optional collections at 1 and 6 months after SBRT. DNA extraction followed by measurement of DNA methylation using capture sequencing will be conducted to investigate the epigenetic regulation of mTOR pathway genes.
Results:
As of August 31, 2026, we have enrolled 36 participants and recruitment is ongoing. We expect to complete data collection and data analysis and start disseminating findings in 2030.
Conclusions:
The study will contribute to exploring the influence of social determinants of health and mTOR pathway gene regulation on post-treatment cancer-related fatigue. The results could pave the way for identification and prioritization of modifiable social determinants of health including dietary exposures, as well as DNA methylation biological markers that enhance understanding of fatigue biology.
Citation
Request queued. Please wait while the file is being generated. It may take some time.
Copyright
© The authors. All rights reserved. This is a privileged document currently under peer-review/community review (or an accepted/rejected manuscript). Authors have provided JMIR Publications with an exclusive license to publish this preprint on it's website for review and ahead-of-print citation purposes only. While the final peer-reviewed paper may be licensed under a cc-by license on publication, at this stage authors and publisher expressively prohibit redistribution of this draft paper other than for review purposes.