Symptom clusters of pain, depressed mood, and fatigue in lung cancer: Assessing the role of cytokine genes

Purpose: Symptom clusters, the multiple, co-occurring symptoms experienced by cancer patients, are debilitating and affects quality of life. We assessed if a panel of immune-response genes may underlie the co-occurrence of severe pain, depressed mood, and fatigue and help identify patients with severe versus non-severe symptom clusters. Methods: Symptoms were assessed at presentation, prior to cancer treatment in 599 newly diagnosed lung cancer patients. We applied cluster analyses to determine the patients with severe versus non-severe symptom clusters of pain, depressed mood, and fatigue. Results: Two homogenous clusters were identified. One hundred sixteen patients (19 %) comprised the severe symptom cluster, reporting high intensity of pain, depressed mood, and fatigue and 183 (30 %) patients reported low intensity of these symptoms. Using Bayesian model averaging methodology, we found that of the 55 single nucleotide polymorphisms assessed, an additive effect of mutant alleles in endothelial nitric oxide synthase (-1474 T/A) (posterior probability of inclusion (PPI) = 0.78, odds ratio (OR) = 0.54, 95 % credible interval (CI) = (0.31, 0.93)); IL1B T-31C (PPI = 0.72, OR = 0.55, 95 % CI = (0.31, 0.97)); TNFR2 Met ¹⁹⁶Arg (PPI = 0.70, OR = 1.85, 95 % CI = (1.03, 3.36)); PTGS2 exon 10+837T > C (PPI = 0.69, OR = 0.54, 95 % CI = (0.28, 0.99)); and IL10RB Lys⁴⁷Glu (PPI = 0.68; OR = 1.74; 95 % CI = (1.04, 2.92)) were predictive for symptom clusters. Conclusions: Genetic polymorphisms may facilitate identification of high-risk patients and development of individualized symptom therapies.