Genetic variations in interleukin-8 and interleukin-10 are associated with pain, depressed mood, and fatigue in lung cancer patients

Context: A report by the National Cancer Institute identified that an important gap in symptom research is the investigation of multiple symptoms of cancer that might identify common biological mechanisms among cancer-related symptoms. Objectives: We applied novel statistical methods to assess whether variants of 37 inflammation genes may serve as biologic markers of risk for severe pain, depressed mood, and fatigue in non-Hispanic white patients with non-small cell lung cancer. Methods: Pain, fatigue, and depressed mood were assessed before cancer treatment. We used a generalized, multivariate, classification tree approach to explore the influence of single-nucleotide polymorphisms in the inflammation genes in pain, depressed mood, and fatigue in lung cancer patients. Results: Among patients with advanced-stage disease, interleukin (IL)-8-T251A was the most relevant genetic factor for pain (odds ratio [OR] = 2.18, 95% CI = 1.34-3.55, P = 0.001), depressed mood (OR = 0.37, 95% CI = 0.14-1.0), and fatigue (OR = 2.07, 95% CI = 1.16-3.70). Among those with early-stage non-small cell lung cancer, variants in the IL-10 receptor were relevant for fatigue among women. Specifically, women with Lys-Glu or Glu-Glu genotype in the IL-10 gene had a 0.49 times lower risk of severe fatigue compared with those with Lys-Lys genotype (OR = 0.49, 95% CI = 0.25-0.92, P = 0.027). Among men with early-stage lung cancer, a marginal significance was observed for IL-1A C-889T, C/T, or T/T genotypes. These men had a lower risk of severe fatigue compared with those with C/C genotype (OR = 0.38, 95% CI = 0.13-1.06). Conclusion: The interaction of multiple inflammation genes, along with nongenetic factors, underlies the occurrence of symptoms. IL-8 and IL-10 may serve as potential targets for treating multiple symptoms of cancer.