Faculty Collaboration Database

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. Cancer Epidemiol Biomarkers Prev 2008 Nov;17(11):3262-7

Date

11/08/2008

Pubmed ID

18990769

Pubmed Central ID

PMC3398799

DOI

10.1158/1055-9965.EPI-08-0125

Scopus ID

2-s2.0-55849095849 (requires institutional sign-in at Scopus site)   53 Citations

Abstract

INTRODUCTION: 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.

Author List

Reyes-Gibby CC, El Osta B, Spitz MR, Parsons H, Kurzrock R, Wu X, Shete S, Bruera E

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Analgesics
Analysis of Variance
Carcinoma, Non-Small-Cell Lung
Case-Control Studies
Chi-Square Distribution
Female
Genetic Variation
Genotype
Humans
Interleukin-6
Interleukin-8
Lung Neoplasms
Male
Pain
Pain Measurement
Palliative Care
Polymorphism, Genetic
Tumor Necrosis Factor-alpha