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.
