Fatigue is the most common post-treatment problem among cancer survivors, affecting a third or more of long-term survivors. Persistent fatigue in survivors may be related in part to overactivation of the inflammatory network;the immune activation that is secondary to the tissue destruction and associated inflammation from many cancer therapies may leave patients vulnerable to the behavioral consequences of proinflammatory cytokines, including fatigue. What is more, a cancer diagnosis and cancer treatments can be quite stressful, and stress and depression can directly enhance the production of proinflammatory cytokines. Fatigue has been well-studied in breast cancer survivors, but far less is known about fatigue in other cancer survivor populations. Furthermore, although several lines of evidence suggest that inflammation plays a significant role in cancer-related fatigue, the data are limited, and longitudinal data in survivors are almost nonexistent. Moreover, the extent to which the incidence and prevalence of fatigue among cancer survivors differs from comparable adults without a cancer history remains an important question;similarly, whether there are differences in inflammation between cancer survivors and adults without a cancer history is unknown. This project provides the opportunity to examine mechanistic connections among fatigue, depression, NF-B activation, health behaviors, and proinflammatory cytokines both cross-sectionally and longitudinally, with initial data on each of these key dimensions collected before cancer treatment, as well as 6 months, 18 months, and 30 months after completion of primary treatment. Subjects will be stage I-IIIA breast cancer survivors, stage I- IIIC colon cancer survivors, and men and women who had a benign diagnosis following an initial abnormal test for breast or colon cancer. The proposed project would provide the first prospective study of inflammation, depression, and fatigue from pretreatment through survivorship in two groups of cancer survivors, as well as a noncancer comparison group.
Specific Aims : (1) To assess the association between inflammation and fatigue cross-sectionally at each of the time points, as well as the extent to which higher levels of inflammatory markers at baseline predict subsequent fatigue;to evaluate these relationships in breast and colon cancer patients, as well as noncancer controls, and to compare the magnitude of both cross-sectional and longitudinal associations across the three groups. (2) To evaluate relationships between past or current syndromal depression and/or depressive symptoms with inflammatory markers, NF-B activation, and fatigue, as well as their association with subsequent inflammation and fatigue. (3) To appraise the relative impact of health-related behaviors (sleep, pain, physical activity, n-6:n-3 dietary fatty acids, central adiposity, and chronic health conditions) as correlates and predictors of syndromal depression and depressive symptoms, inflammatory markers, and fatigue. Fatigue is the most common post-treatment problem among cancer survivors, affecting a third or more of long- term survivors. Several lines of evidence suggest that immune system activation plays a significant role in cancer-related fatigue;however, the data are limited and longitudinal data as well as data comparing survivors to noncancer controls are almost nonexistent. The proposed project would provide the first prospective study of inflammation, depression, fatigue, and health-related behaviors from pretreatment through survivorship in two groups of cancer survivors, as well as a noncancer comparison group.
Specific Aims : (1) To assess the association between inflammation and fatigue cross-sectionally at each of the time points, as well as the extent to which higher levels of inflammatory markers at baseline predict subsequent fatigue;to evaluate these relationships in breast and colon cancer patients, as well as noncancer controls, and to compare the magnitude of both cross-sectional and longitudinal associations across the three groups. (2) To evaluate relationships between past or current syndromal depression and/or depressive symptoms with inflammatory markers, NF-κB activation, and fatigue, as well as their association with subsequent inflammation and fatigue. (3) To appraise the relative impact of health related behaviors (sleep, pain, physical activity, n-6:n-3 dietary fatty acids, central adiposity, and chronic health conditions) as correlates and predictors of syndromal depression and depressive symptoms, inflammatory markers, and fatigue.

Public Health Relevance

Fatigue is the most common post-treatment problem among cancer survivors, affecting a third or more of longterm survivors. Several lines of evidence suggest that immune system activation plays a significant role in cancer-related fatigue;however, the data are limited and longitudinal data as well as data comparing survivors to noncancer controls are almost nonexistent. The proposed project would provide the first prospective study of inflammation, depression, fatigue, and health-related behaviors from pretreatment through survivorship in two groups of cancer survivors, as well as a noncancer comparison group.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA131029-06S1
Application #
8625003
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Mc Donald, Paige A
Project Start
2008-05-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
6
Fiscal Year
2013
Total Cost
$50,036
Indirect Cost
$17,439
Name
Ohio State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Kiecolt-Glaser, Janice K; Bennett, Jeanette M; Andridge, Rebecca et al. (2014) Yoga's impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. J Clin Oncol 32:1040-9
Fagundes, Christopher P; Jaremka, Lisa M; Glaser, Ronald et al. (2014) Attachment anxiety is related to Epstein-Barr virus latency. Brain Behav Immun 41:232-8
Jaremka, Lisa M; Andridge, Rebecca R; Fagundes, Christopher P et al. (2014) Pain, depression, and fatigue: loneliness as a longitudinal risk factor. Health Psychol 33:948-57
Jaremka, Lisa M; Peng, Juan; Bornstein, Robert et al. (2014) Cognitive problems among breast cancer survivors: loneliness enhances risk. Psychooncology 23:1356-64
Hughes, Spenser; Jaremka, Lisa M; Alfano, Catherine M et al. (2014) Social support predicts inflammation, pain, and depressive symptoms: longitudinal relationships among breast cancer survivors. Psychoneuroendocrinology 42:38-44
Kiecolt-Glaser, Janice K; Glaser, Ronald; Christian, Lisa M (2014) Omega-3 fatty acids and stress-induced immune dysregulation: implications for wound healing. Mil Med 179:129-33
Fagundes, Christopher P; Jaremka, Lisa M; Malarkey, William B et al. (2014) Attachment style and respiratory sinus arrhythmia predict post-treatment quality of life in breast cancer survivors. Psychooncology 23:820-6
Fagundes, Christopher P; Glaser, Ronald; Kiecolt-Glaser, Janice K (2013) Stressful early life experiences and immune dysregulation across the lifespan. Brain Behav Immun 27:8-12
Fagundes, Christopher P; Glaser, Ronald; Malarkey, William B et al. (2013) Childhood adversity and herpesvirus latency in breast cancer survivors. Health Psychol 32:337-44
Jaremka, Lisa M; Lindgren, Monica E; Kiecolt-Glaser, Janice K (2013) Synergistic relationships among stress, depression, and troubled relationships: insights from psychoneuroimmunology. Depress Anxiety 30:288-96

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