title: Disturbed sleep in pediatric patients with leukemia: the potential role of interleukin-6 (-174GC) and tumor necrosis factor (-308GA) polymorphism.
abstract: OBJECTIVE
  To explore an association between sleep quality in children and adolescents undergoing therapy for acute lymphoblastic leukemia (ALL) and polymorphisms in two proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor (TNF).
  
  
  METHODS
  Retrospective exploratory analysis using data from a multi-institutional prospective study comparing objective sleep measures by actigraphy over 10 days with retrospective genotyping of IL-6 (-174GC) and TNF (-308GA).
  
  
  METHODS
  Pediatric oncology centers in the southeastern and southwestern United States and in Canada.
  
  
  METHODS
  88 children or adolescents with ALL.
  
  
  METHODS
  Secondary analysis of 88 patients (ages 5-18) with sleep quality measured by actigraphy over 10 days in their home environment and retrospective DNA genotyping.
  
  
  METHODS
  Sleep variables and genotype.
  
  
  RESULTS
  IL-6 promoter (-174G>C) C allele was associated with fewer total daily sleep minutes (p = 0.028) and fewer daily nap minutes (p < 0.01). Patients with the TNF genotype AA had 28.2 more minutes of wake after sleep onset (p = 0.015), 3.4 more nocturnal wake episodes (p = 0.026), and a 5% lower sleep efficiency rate (p = 0.03) than their GA genotype counterparts.
  
  
  CONCLUSIONS
  Patients with the TNF (-308G>A) or IL-6 (-174G>C) polymorphisms demonstrated disturbed sleep. This study is the first to find a relationship between these two cytokines and disturbed sleep in children and adolescents with cancer.
  
  
  CONCLUSIONS
  Disturbed sleep among pediatric patients with cancer is multifactoral and includes interactions among environment, medications, and genotype. Additional research should explore serum proinflammatory cytokine levels and the influence of mood and worry on sleep.
authors.affiliation: Department of Hematology/Oncology, Cook Children's Medical Center, Fort Worth, TX, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Vallance
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Valerie McLaughlin
authors.initials: VM
authors.lastname: Crabtree
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Hinds
authors.forename: Belinda N
authors.initials: BN
authors.lastname: Mandrell
mesh_terms: D056044:Actigraphy; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000628:therapy; D012189:Retrospective Studies; D012893:Sleep Wake Disorders / Q000150:complications / Q000235:genetics*; D048069:Tumor Necrosis Factors / Q000235:genetics*
chemical_list: D015850:Interleukin-6; D048069:Tumor Necrosis Factors