Role of inflammation gene polymorphisms on pain severity in lung cancer patients.
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 > or = 7). Advanced stage of disease [odds ratio (OR), 2.34; 95% confidence interval (95% CI), 1.50-3.65; P = 0.001], age < or = 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 TNFalpha -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.
Department of Epidemiology, Division of Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Unit 1340, 1155 Pressler Street, Houston, TX 77030-4009, USA. creyes@mdanderson.org
Cielito C
CC
Reyes-Gibby
Margaret R
MR
Spitz
Sriram
S
Yennurajalingam
Michael
M
Swartz
Jian
J
Gu
Xifeng
X
Wu
Eduardo
E
Bruera
Sanjay
S
Shete
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000235:genetics*; D010147:Pain Measurement; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide