Genetic and Nongenetic Covariates of Pain Severity in Patients with Adenocarcinoma of the Pancreas: Assessing the Influence of Cytokine Genes

We previously demonstrated that select cytokine gene polymorphisms in interleukin (IL)-8 are a significant predictor of pain and analgesia in patients with lung cancer. This study explores the role of 13 potentially functional polymorphisms in cytokine genes, including IL-1β, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α, and nuclear factor kappa-B subunit 1, in pain severity in patients with pancreatic cancer. We evaluated a series of patients with histologically confirmed adenocarcinoma of the pancreas (n = 484), who had completed a self-administered survey of pain before initiating any cancer treatment. DNA (n = 156) available for a subset of white patients was assayed and assessed for association with pain severity. Results showed that 26% (128 of 484) reported experiencing severe pain (score of >7 on a 0-10 scale). Severe pain varied by the stage of disease (odds ratio [OR] Stage II = 4.02, 95% confidence interval (CI) = 1.07, 15.07; Stage III = 5.02, 95% CI = 1.28, 19.61; Stage IV = 6.90, 95% CI = 1.96, 24.29), ethnicity (OR non-Hispanic blacks = 3.67; 95% CI = 1.44, 9.38), reports of depressed mood (OR = 1.94; 95% CI = 1.09, 3.43), and female sex (OR = 1.78; 95% CI = 1.04, 3.05). Controlling for these covariates, IL8-251T/A (OR = 2.43, 95% CI = 1.3, 4.7, P < 0.009) significantly predicted severe pain in a subset of white patients. When we adjusted for reported analgesic use, we found that IL8-251T/A persisted as a predictor for severe pain, with carriers of TT and AT genotypes having more than a threefold risk (OR = 3.23, 95% CI = 1.4, 4.7) for severe pain relative to the AA genotypes. We provide preliminary evidence of the role of IL-8 in the severity of pain in pancreatic cancer patients. Additional studies are needed in larger cohorts of patients.