Faculty Collaboration Database

Genetic and nongenetic covariates of pain severity in patients with adenocarcinoma of the pancreas: assessing the influence of cytokine genes. J Pain Symptom Manage 2009 Dec;38(6):894-902

Date

08/21/2009

Pubmed ID

19692203

Pubmed Central ID

PMC2795073

DOI

10.1016/j.jpainsymman.2009.04.019

Scopus ID

2-s2.0-71249086891 (requires institutional sign-in at Scopus site)   38 Citations

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.

Author List

Reyes-Gibby CC, Shete S, Yennurajalingam S, Frazier M, Bruera E, Kurzrock R, Crane CH, Abbruzzese J, Evans D, Spitz MR

Authors

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Aged
Analgesics
Cytokines
Drug Utilization
False Positive Reactions
Female
Genetic Variation
Humans
Male
Middle Aged
Pain
Pain Measurement
Pancreatic Neoplasms
Polymorphism, Single Nucleotide