title: Genetic and nongenetic covariates of pain severity in patients with adenocarcinoma of the pancreas: assessing the influence of cytokine genes.
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-1beta, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-alpha, 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.
authors.affiliation: Department of Epidemiology, Division of Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA. creyes@mdanderson.org
authors.forename: Cielito C
authors.initials: CC
authors.lastname: Reyes-Gibby
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shete
authors.forename: Sriram
authors.initials: S
authors.lastname: Yennurajalingam
authors.forename: Marsha
authors.initials: M
authors.lastname: Frazier
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bruera
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Crane
authors.forename: James
authors.initials: J
authors.lastname: Abbruzzese
authors.forename: Douglas
authors.initials: D
authors.lastname: Evans
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
mesh_terms: D000230:Adenocarcinoma / Q000150:complications* / Q000235:genetics*; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics*; D004363:Drug Utilization; D005189:False Positive Reactions; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D010147:Pain Measurement; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000700:Analgesics; D016207:Cytokines
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