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Chest. 2005 Jul;128(1):445-52.

Alpha1-antitrypsin and neutrophil elastase imbalance and lung cancer risk.

Author information

1
Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. yang.ping@mayo.edu

Erratum in

  • Chest. 2006 Jan;129(1):216. Krowka, Michael J [added].

Abstract

OBJECTIVE:

Imbalance between alpha(1)-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 alpha(1)-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 alpha(1)-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.

PMID:
16002971
DOI:
10.1378/chest.128.1.445
[Indexed for MEDLINE]

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