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Evidence of an Association Between Pro- and Anti-Inflammatory Cytokine Genes and a Symptom Cluster of Pain, Fatigue, Sleep Disturbance, and Depression

Abstract

The experience of multiple symptoms related to `sickness behavior' (e.g., pain, fatigue, sleep disturbance, and depression) can have a negative impact on an individual's functional status and quality of life (QOL). A greater understanding of the mechanisms that underlie inter-individual variability in this symptom experience is needed. The purposes of this study were to determine if distinct classes of individuals could be identified based on their experience with the symptom cluster of pain, fatigue, sleep disturbance and depression; to determine if these classes differed on demographic and clinical characteristics; and to determine if variations in a number of pro- and anti- inflammatory cytokine genes were associated with latent class membership.

This descriptive, correlational study used self report measures of pain, fatigue, sleep disturbance, and depression to evaluate symptoms in 168 outpatients with breast, prostate, lung, or brain cancer and 85 family caregivers (FCs). Three relatively distinct classes were identified using latent class profile analysis (LCPA): those who reported low depression and low pain (83.0%), those who reported high depression and low pain (4.7%), and those who reported high levels of all four symptoms (12.3%). The minor allele of IL4 rs2243248 was associated with membership in the "All high" class along with lower Karnofsky Performance Status (KPS) score, higher number of comorbid conditions, being a patient (versus a FC), and being female. The minor allele of IL8 rs2227306 was associated with membership in the "High depression and low pain" class.

Findings suggest that LCPA can be used to differentiate distinct phenotypes based on a symptom cluster associated with sickness behavior. Identification of this distinct phenotype reveals new evidence for the role of IL4 and IL8 in the modulation of a sickness behavior symptom cluster in oncology patients and their FCs.

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