Role of Inflammation Gene Polymorphisms on Pain Severity in Lung Cancer Patients
- 1 October 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Epidemiology, Biomarkers & Prevention
- Vol. 18 (10), 2636-2642
- https://doi.org/10.1158/1055-9965.epi-09-0426
Abstract
Many of the same inflammatory factors that promote tumor growth are also hypothesized to function as pain modulators. There is substantial interindividual variation in pain severity in cancer patients. Therefore, we evaluated 59 single nucleotide polymorphisms in 37 inflammation genes in newly diagnosed non-Hispanic Caucasian lung cancer patients (n = 667) and assessed their association with pain severity. Patients rated their pain “during the past week” on an 11-point numeric scale (0 = “no pain” and 10 = “pain as bad as you can imagine”) at presentation before initiating cancer therapy. Reported analgesic use was abstracted from charts and converted to morphine equivalent daily dose. Results showed that 16% of the patients reported severe pain (score ≥7). Advanced stage of disease [odds ratio (OR), 2.34; 95% confidence interval (95% CI), 1.50-3.65; P = 0.001], age ≤50 years (OR, 2.10; 95% CI, 1.32-3.30; P = 0.002), reports of depressed mood (OR, 3.68; 95% CI, 1.96-6.93; P = 0.001), fatigue (OR, 3.72; 95% CI, 2.36-5.87; P = 0.001), and morphine equivalent daily dose (OR, 1.02; 95% CI, 1.01-1.03) were significantly correlated with severe pain. Controlling for these nongenetic covariates, we found that patients with CC genotypes for PTGS2 exon10+837T>C (rs5275) were at lower risk for severe pain (OR, 0.33; 95% CI, 0.11-0.97) and an additive model for TNFα −308GA (rs1800629; OR, 1.67; 95% CI, 1.08-2.58) and NFKBIA Ex6+50C>T (rs8904) was predictive of severe pain (OR, 0.64; 95% CI, 0.43-0.93). In a multigene analysis, we found a gene-dose effect, with each protective genotype reducing the risk for severe pain by as much as 38%. This study suggests the importance of inflammation gene polymorphisms in modulating pain severity. Additional studies are needed to validate our findings. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2636–42)Keywords
This publication has 50 references indexed in Scilit:
- The Influence of Tumor Necrosis Factor-α −308 G/A and IL-6 −174 G/C on Pain and Analgesia Response in Lung Cancer Patients Receiving Supportive CareCancer Epidemiology, Biomarkers & Prevention, 2008
- Molecular epidemiology, cancer-related symptoms, and cytokines pathwayThe Lancet Oncology, 2008
- Cytokine Genes and Pain Severity in Lung Cancer: Exploring the Influence of TNF-α-308 G/A IL6-174G/C and IL8-251T/ACancer Epidemiology, Biomarkers & Prevention, 2007
- Pain, Depression, and Fatigue in Community-Dwelling Adults With and Without a History of CancerJournal of Pain and Symptom Management, 2006
- Reduced levels of antiinflammatory cytokines in patients with chronic widespread painArthritis & Rheumatism, 2006
- Increased production of nitric oxide stimulated by interferon-γ from peripheral blood monocytes in patients with complex regional pain syndromeNeuroscience Letters, 2002
- Pain Measurement Tools and Methods in Clinical Research in Palliative CareJournal of Pain and Symptom Management, 2002
- Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciaticaEuropean Spine Journal, 2001
- Temporal Presentation of Chronic Cancer Pain: Transitory Pains on Admission to a Multidisciplinary Pain ClinicJournal of Pain and Symptom Management, 1999
- Cytokine-to-brain communication: A review & analysis of alternative mechanismsLife Sciences, 1995