α1-antitrypsin and neutrophil elastase imbalance and lung cancer risk

Ping Yang, William R. Bamlet, Zhifu Sun, Jon O. Ebbert, Marie Christine Aubry, William R. Taylor, Randolph S. Marks, Claude Deschamps, Stephen J. Swensen, Eric D. Wieben, Julie M. Cunningham, Lee Joseph Melton, Mariza De Andrade

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Objective: Imbalance between α1-antitrypsin and neutrophil elastase is an underlying cause of lung tissue damage that may create a favorable host environment for carcinogenesis. We conducted a case-control study to investigate whether genetic variations indicative of α1- antitrypsin deficiency (A1ATD) or an excess of neutrophil elastase modify lung cancer risk Design: The case patients were 305 consecutively identified primary lung cancer patients, and the control subjects were 338 community residents. Protease inhibitor-1 (PI1), encoding α1-antitrypsin, was typed by an isoelectric focusing assay. Neutrophil elastase-2 (ELA2), encoding neutrophil elastase, was typed by two single-nucleotide polymorphism sites. Multivariable logistic regression models tested the independent and interactive effects of PI1, ELA2, tobacco smoke exposure, COPD, and family history of lung cancer Results: Sex and ethnicity were comparable between case patients and control subjects, but case patients were more likely to be smokers, and to have a history of COPD, environmental tobacco smoke exposure, and a positive family history of lung cancer. Haplotype analysis indicated an overall strong association between the two ELA2 markers and lung cancer risk. Our best-fitting model showed significant and independent effects of the PI1-deficient allele (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4 to 3.0) and the ELA2 T-G haplotype (OR, 4.1; 95% CI, 1.9 to 8.9) on lung cancer risk, and an increased risk (OR, 2.6; 95% CI, 2.4 to 2.8) for individuals carrying both a PI1-deficient allele and a G-G haplotype Conclusions: Genotypes indicative of A1ATD and/or an excess of neutrophil elastase are significantly associated with lung cancer risk. Our findings may provide opportunities to better understand the mechanisms of lung cancer development and risk reduction.

Original languageEnglish (US)
Pages (from-to)445-452
Number of pages8
JournalChest
Volume128
Issue number1
DOIs
StatePublished - Jul 2005

Keywords

  • Chronic obstructive
  • Leukocyte elastase
  • Lung neoplasm
  • Pulmonary disease
  • Tobacco smoking
  • α-antitrypsin deficiency

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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