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Ann Thorac Surg 2005;79:1704-1710
© 2005 The Society of Thoracic Surgeons

Original articles: General thoracic

Inflammatory Gene Polymorphisms Influence Risk of Postoperative Morbidity After Lung Resection

Andrew D. Shaw, MBa,*, Ara A. Vaporciyan, MDb, Xifeng Wu, MDc, Terri M. King, PhDe, Margaret R. Spitz, MDc, Joe B. Putnam, MDf, Burton F. Dickey, MDd

a Division of Anesthesiology and Critical Care Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
b Department of Thoracic Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
c Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
d Department of Pulmonary Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
e Department of Internal Medicine, University of Texas-Houston Medical School, Houston, Texas
f Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee

Accepted for publication October 12, 2004.

* Address reprint requests to Dr Shaw, Dept of Critical Care Medicine, Unit 112, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (E-mail: ashaw{at}mdanderson.org).

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.




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