TY - JOUR
T1 - Prospective analyses of cytokine mediation of sleep and survival in the context of advanced cancer
AU - Steel, Jennifer L.
AU - Terhorst, Lauren
AU - Collins, Kevin P.
AU - Geller, David A.
AU - Vodovotz, Yoram
AU - Kim, Juliana
AU - Krane, Andrew
AU - Antoni, Michael
AU - Marsh, James W.
AU - Burke, Lora E.
AU - Butterfield, Lisa H.
AU - Penedo, Frank J.
AU - Buysse, Daniel J.
AU - Tsung, Allan
N1 - Publisher Copyright:
© Lippincott Williams & Wilkins.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Objective The aims of this study were to examine the potential association between sleep problems, symptom burden, and survival in patients with advanced cancer. Methods A prospective study of 294 patients with gastrointestinal cancer administered questionnaires assessing sleep, depression, anxiety, stress, pain, fatigue, and health-related quality of life. Serum levels of cytokines including interleukin (IL)-1α, IL-1β, tumor necrosis factor α, IL-10, IL-2, and interferon-γ were measured to assess biological mediation between sleep and survival. Survival was measured as time from diagnosis to death. Results Fifty-nine percent of patients reported poor sleep quality, 53% reported poor sleep efficiency, 39% reported sleep latency greater than 30 minutes, and 45% reported sleeping less than 6 hours or greater than 10 hours. We found a significant association between sleep duration and symptom burden. Shorter sleep duration was significantly associated with higher levels of fatigue (r = -0.169, p =.01), pain (r = -0.302, p =.01), anxiety (r = -0.182, p =.01), depression (r = -0.172, p =.003), and lower levels of quality of life (r = 0.240, p =.01). After adjustment for demographic, psychological, and disease-specific factors, short sleep duration was associated with reduced survival (hazard ratio [HR] linear = 0.485, 95% confidence interval = 0.275-0.857) and there was also evidence for a quadratic pattern (HR quadrati = 1.064, 95% confidence interval = 1.015-1.115) suggesting a curvilinear relationship between sleep duration and survival. Interleukin 2 was the only cytokine significantly related to survival (HR = 1.01, p =.003) and sleep duration (β = -30.11, p =.027). When of IL-2 was added to the multivariable model, short and long sleep (β = -0.557, p =.097; β = 0.046, p =.114) were no longer significantly related to survival, suggesting mediation by IL-2. Conclusion Sleep duration was associated with symptom burden and poorer survival and IL-2 was found to mediate the association between sleep and survival. Screening and treatment of sleep problems in patients diagnosed with cancer are warranted.
AB - Objective The aims of this study were to examine the potential association between sleep problems, symptom burden, and survival in patients with advanced cancer. Methods A prospective study of 294 patients with gastrointestinal cancer administered questionnaires assessing sleep, depression, anxiety, stress, pain, fatigue, and health-related quality of life. Serum levels of cytokines including interleukin (IL)-1α, IL-1β, tumor necrosis factor α, IL-10, IL-2, and interferon-γ were measured to assess biological mediation between sleep and survival. Survival was measured as time from diagnosis to death. Results Fifty-nine percent of patients reported poor sleep quality, 53% reported poor sleep efficiency, 39% reported sleep latency greater than 30 minutes, and 45% reported sleeping less than 6 hours or greater than 10 hours. We found a significant association between sleep duration and symptom burden. Shorter sleep duration was significantly associated with higher levels of fatigue (r = -0.169, p =.01), pain (r = -0.302, p =.01), anxiety (r = -0.182, p =.01), depression (r = -0.172, p =.003), and lower levels of quality of life (r = 0.240, p =.01). After adjustment for demographic, psychological, and disease-specific factors, short sleep duration was associated with reduced survival (hazard ratio [HR] linear = 0.485, 95% confidence interval = 0.275-0.857) and there was also evidence for a quadratic pattern (HR quadrati = 1.064, 95% confidence interval = 1.015-1.115) suggesting a curvilinear relationship between sleep duration and survival. Interleukin 2 was the only cytokine significantly related to survival (HR = 1.01, p =.003) and sleep duration (β = -30.11, p =.027). When of IL-2 was added to the multivariable model, short and long sleep (β = -0.557, p =.097; β = 0.046, p =.114) were no longer significantly related to survival, suggesting mediation by IL-2. Conclusion Sleep duration was associated with symptom burden and poorer survival and IL-2 was found to mediate the association between sleep and survival. Screening and treatment of sleep problems in patients diagnosed with cancer are warranted.
KW - BMI = body mass index
KW - CRP = C-reactive protein
KW - Cancer
KW - Cytokines
KW - FACT-Hep = Functional Assessment of Cancer Therapy-Hepatobiliary
KW - IL = interleukin
KW - MinDC = minimum detectable concentration
KW - Mortality
KW - Sleep duration
KW - Sleep problems
KW - Sleep regulation
UR - http://www.scopus.com/inward/record.url?scp=85048711033&partnerID=8YFLogxK
U2 - 10.1097/PSY.0000000000000579
DO - 10.1097/PSY.0000000000000579
M3 - Article
C2 - 29621045
AN - SCOPUS:85048711033
SN - 0033-3174
VL - 80
SP - 483
EP - 491
JO - Psychosomatic Medicine
JF - Psychosomatic Medicine
IS - 5
ER -