title: Cytokine genetic variations and fatigue among patients with breast cancer.
abstract: OBJECTIVE
  Fatigue is a common adverse effect of cancer treatment and may persist for years after treatment completion. However, risk factors for post-treatment fatigue have not been determined. On the basis of studies suggesting an inflammatory basis for fatigue, this study tested the hypothesis that expression-regulating polymorphisms in proinflammatory cytokine genes would predict post-treatment fatigue in breast cancer survivors.
  
  
  METHODS
  Women diagnosed with early-stage breast cancer (n = 171) completed questionnaires to assess fatigue and other behavioral symptoms (ie, depressive symptoms, memory complaints, sleep disturbance) and provided blood for genotyping within 3 months after primary treatment. Genomic DNA was extracted from peripheral-blood leukocytes and assayed for single nucleotide polymorphisms (SNPs) in the promoter regions of three cytokine genes: ILB -511 C>T (rs16944), IL6 -174 G>C (rs1800795), and TNF -308 G>A (rs1800629). An additive genetic risk score was computed by summing the number of high-expression alleles (zero, one, or two) across all three polymorphisms.
  
  
  RESULTS
  The genetic risk index was significantly associated with fatigue; as the number of high-expression alleles increased, so did self-reported fatigue severity (P = .002). Analyses of individual SNPs showed that TNF -308 and IL6 -174 were independently associated with fatigue (P = .032). The genetic risk index was also associated with depressive symptoms (P = .007) and memory complaints (P = .016).
  
  
  CONCLUSIONS
  These findings further implicate inflammatory processes as contributors to cancer-related fatigue and suggest a new strategy for identifying and treating patients at risk for this symptom based on genetic variants in proinflammatory cytokine genes.
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095-1563, USA. jbower@ucla.edu
authors.forename: Julienne E
authors.initials: JE
authors.lastname: Bower
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.forename: Michael R
authors.initials: MR
authors.lastname: Irwin
authors.forename: Steven
authors.initials: S
authors.lastname: Castellon
authors.forename: Jesusa
authors.initials: J
authors.lastname: Arevalo
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016207:Cytokines / Q000235:genetics*; D005221:Fatigue / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide
chemical_list: D016207:Cytokines