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

• Published in: Journal of pain and symptom management 2009-12, Vol.38 (6), p.894-902
• Main Authors: Reyes-Gibby, Cielito C., DrPH, Shete, Sanjay, PhD, Yennurajalingam, Sriram, MD, Frazier, Marsha, PhD, Bruera, Eduardo, MD, Kurzrock, Razelle, MD, Crane, Christopher H., MD, Abbruzzese, James, MD, Evans, Douglas, MD, Spitz, Margaret R., MD
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - complications; Adenocarcinoma - genetics; Aged; analgesia; Analgesics - therapeutic use; Anesthesia & Perioperative Care; Biological and medical sciences; cancer; cytokines; Cytokines - genetics; Drug Utilization; epidemiology; False Positive Reactions; Female; Genes; Genetic Variation; Humans; Male; Medical sciences; Middle Aged; molecular epidemiology; Pain; Pain - epidemiology; Pain - etiology; Pain - genetics; Pain Measurement; Pain Medicine; Pancreatic cancer; Pancreatic Neoplasms - complications; Pancreatic Neoplasms - genetics; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide; Severity
• ISSN: 0885-3924; 1873-6513
• DOI: 10.1016/j.jpainsymman.2009.04.019

Abstract 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.