The Influence of Tumor Necrosis Factor-α-308 G/A and IL-6-174 G/C on Pain and Analgesia Response in Lung Cancer Patients Receiving Supportive Care

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