Inflammatory gene polymorphisms influence risk of postoperative morbidity after lung resection.
BACKGROUND
Polymorphisms in genes encoding proteins involved in the inflammatory response may lead to a differential response to a noxious stimulus. We hypothesized that proinflammatory alleles at candidate loci would predispose patients undergoing lung resection to cardiopulmonary complications with a presumed inflammatory cause.


METHODS
We determined the genotypes at six candidate loci in 155 patients who underwent 160 lung resection operations at our center. We correlated these results with data from our clinical database, constructed a model predicting the risk of postoperative complications, and assessed its adequacy using receiver operating characteristic curve methodology.


RESULTS
Preexisting cardiovascular disease (p < 0.001), primary lung cancer (p = 0.009), extent of lung resection (p = 0.042), interleukin 6 genotype (p = 0.017), and tumor necrosis factor genotype (p = 0.005) were significantly associated with complications. The odds ratio for complications for rare allele homozygosity was 3.9 (95% confidence interval, 1.4 to 10.4) for interleukin 6 and 15.3 (95% confidence interval, 1.7 to 131.4) for tumor necrosis factor. In multivariate analysis we found that cardiovascular disease (p < 0.001; odds ratio, 4.0 [95% confidence interval, 1.9 to 8.6]), interleukin 6 genotype (p = 0.027; odds ratio, 1.8 [95% confidence interval, 1.1 to 3.1]), and tumor necrosis factor genotype (p = 0.011; odds ratio, 2.5 [95% confidence interval, 1.2 to 5.1]) were independently predictive of complications, with an area under the receiver operating characteristic curve for the entire model of 0.765.


CONCLUSIONS
Carriage of specific alleles, and homozygosity in particular, at loci within the interleukin 6 and tumor necrosis factor genes appears to contribute to the risk of experiencing an adverse event after lung resection.
Shaw
Andrew D
AD
Division of Anesthesiology and Critical Care Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ashaw@mdanderson.org
Vaporciyan
Ara A
AA
Wu
Xifeng
X
King
Terri M
TM
Spitz
Margaret R
MR
Putnam
Joe B
JB
Dickey
Burton F
BF
D000368:Aged; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008175:Lung Neoplasms / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000453:epidemiology*; D015183:Restriction Mapping; D012189:Retrospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D052250:Nitric Oxide Synthase Type III