Fatigue is one of the most common and severe symptoms reported in oncology patients, particularly in women with breast cancer. Fatigue not only occurs in oncology patients undergoing active treatment, but persists into survivorship. Fatigue is associated with decrements in quality of life (QOL) and results in significant decrements in function and lost productivity. Fatigue increases with age and is more pronounced in women. Specifically related to this R21 application, age is one of the most common risk factors associated with morning and evening fatigue in women with breast cancer. Recent evidence suggests that DNA methylation is a novel and accurate biomarker of aging. Building on our recently collected in-depth phenotypic (i.e., morning fatigue, evening fatigue, clinical, treatment, demographic) and molecular (i.e., DNA methylation) data, the aims proposed in this R21 application provide a unique opportunity to identify novel associations among DNA methylation profiles for aging and morning fatigue and evening fatigue in women with breast cancer. Thus, the specific aims of this study, in a sample of women with breast cancer (n=251) with self-report measures of morning fatigue, evening fatigue as well as genome-wide DNA methylome data available for analysis, are to: determine the number of latent classes using growth mixture modeling for morning fatigue and for evening fatigue; and to estimate the association between a DNA methylation profile of aging and morning fatigue group membership and evening fatigue group membership. This pilot study, which capitalizes on our experience with the novel phenotypic and molecular studies of morning fatigue and of evening fatigue in patients with cancer, will be the first to evaluate an epigenetic profile for biological aging. The proposed project will provide the necessary preliminary data to perform a larger study to validate (i.e., in an additional 1104 breast cancer patients) and extend (i.e., examine the impact of treatment characteristics, compare active treatment versus survivorship in the 1104 breast cancer patients) these findings. This subsequent large scale study will provide critical information that will be used to identify patients at highest risk for this debilitating symptom. Most importantly, this line of inquiry will address important gaps in our understanding of the biological mechanisms that underlie the inter-relationships among aging and morning fatigue and evening fatigue.
Fatigue is one of the most common and severe symptoms reported in oncology patients, particularly in women with breast cancer. Fatigued cancer survivors display physiological functioning similar to individuals two- decades older. Recent evidence suggests that DNA methylation, an epigenetic marker that captures aggregate responses to genetic and environmental exposures, is a novel and accurate biomarker that can be used to examine the biological adaptations to aging. Building on our recently collected in-depth phenotypic (i.e., morning fatigue, evening fatigue, clinical, treatment, demographic) and molecular (i.e., DNA methylation) data, the aims proposed in this R21 application provide a unique opportunity to identify novel associations among DNA methylation profiles for aging and diurnal variations (i.e., morning and evening) fatigue in women with breast cancer. This line of inquiry will address important gaps in our understanding of the biological mechanisms that underlie the inter-relationships among morning and evening fatigue and aging.
