Prospective analyses of cytokine mediation of sleep and survival in the context of advanced cancer

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.