title: The influence of tumor necrosis factor-alpha -308 G/A and IL-6 -174 G/C on pain and analgesia response in lung cancer patients receiving supportive care.
abstract: BACKGROUND
  We previously showed that select cytokine gene polymorphisms are a significant predictor for pain reported at initial presentation in 446 white patients newly diagnosed with non-small cell lung cancer. This follow-up study explores the extent to which polymorphisms in tumor necrosis factor-alpha (TNF- alpha-308 G/A), interleukin (IL)-6 -174G/C, and IL-8 -251T/A could explain variability in pain and analgesic response among those patients (n = 140) subsequently referred for pain treatment.
  
  
  METHODS
  Pain severity (0, no pain; 10, worst pain) was assessed at initial consultation and at follow-up visit. The total dose of opioids at the time of first-follow up visit (30 days postconsult) was converted to an equivalent dose of parenteral morphine.
  
  
  RESULTS
  Forty-one percent (57 of 140) of the patients reported severe pain (score > 7/10) at initial consultation (mean, 5.5), which significantly decreased to 25% (mean, 4) at first follow-up visit (McNemar = P < 0.001). Polymorphisms in TNF and IL-6 were significantly associated with pain severity (for TNF GG, 4.12; GA, 5.38; AA, 5.50; P = 0.04) and with morphine equivalent daily dose (IL-6 GG, 69.61; GC, 73.17; CC, 181.67; P = 0.004), respectively. Adjusting for demographic and clinical variables, variant alleles in TNFalpha -308 G/A remained significantly associated with pain severity (b = 0.226; P = 0.036) and carriers of the IL-6 -174C/C genotypes required 4.7 times higher dose of opioids for pain relief (odds ratio, 4.7; 95% confidence interval, 1.2;15.0) relative to GG and GC genotypes.
  
  
  CONCLUSIONS
  We provide preliminary evidence of the influence of cytokine genes on pain and response to analgesia in lung cancer patients. Additional studies are needed to validate our findings. The long-term application is to tailored pain therapies.
authors.affiliation: Department of Epidemiology, Division of Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, 1155 Pressler Street-Unit 1340, Houston, TX 77030-4009, USA. creyes@mdanderson.org
authors.forename: Cielito C
authors.initials: CC
authors.lastname: Reyes-Gibby
authors.forename: Badi
authors.initials: B
authors.lastname: El Osta
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Henrique
authors.initials: H
authors.lastname: Parsons
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shete
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bruera
mesh_terms: D000700:Analgesics / Q000627:therapeutic use; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000628:therapy*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000235:genetics*; D010147:Pain Measurement; D010166:Palliative Care; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000700:Analgesics; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha