Cytokine genes and pain severity in lung cancer: Exploring the influence of TNF-α-308 G/A IL6-174G/C and IL8-251T/A

Introduction: Cytokines, aberrantly produced by cancer cells, have recently been implicated in the severity of cancer-related pain. We explored if polymorphisms in candidate cytokine genes could explain variability in self-reported pain in lung cancer patients of all stages. Methods: Pain, clinical, and demographic variables were assessed at presentation and before any cancer treatment in 446 Whites, 125 African-Americans, and 35 Hispanics with newly diagnosed non- small cell lung cancer. We genotyped functional single nucleotide polymorphisms in tumor necrosis factor-α (TNF-α -308 G/A), interleukin-6 (IL-6) -174G/C, and IL-8 -251T/A and determined their associations with pain severity. Results: More African-Americans (35.5%) reported severe pain (score ≥7 on a 0-10 scale) relative to Hispanics (20%) and Whites (17%; P < 0.001). We did not observe any significant association between genotypes in TNF-α, IL-6, and IL-8 and severe pain for either African-Americans or Hispanics, possibly due to small sample sizes. However, we observed that IL-8 (TT, 13%; TA + AA, 87%; P = 0.04) was significantly associated with severe pain among White patients. Logistic regression analyses showed that after controlling for epidemiologic (age and sex), clinical (stage of disease, comorbidities), and symptom (depressed mood and fatigue) variables known to influence pain severity, variant alleles in IL-8 -251T/A [odds ratio (OR), 2.35; 95% confidence interval (95% CI), 1.10-5.03; P = 0.03] persisted as a significant factor for severe pain for White patients. Conclusions: In this preliminary analysis, we found evidence of the influence of cytokine genes on pain in White patients with lung cancer. Additional larger studies are needed to validate our findings. The longterm application is to tailored pain therapies.