TY - JOUR
T1 - α1-antitrypsin and neutrophil elastase imbalance and lung cancer risk
AU - Yang, Ping
AU - Bamlet, William R.
AU - Sun, Zhifu
AU - Ebbert, Jon O.
AU - Aubry, Marie Christine
AU - Taylor, William R.
AU - Marks, Randolph S.
AU - Deschamps, Claude
AU - Swensen, Stephen J.
AU - Wieben, Eric D.
AU - Cunningham, Julie M.
AU - Melton, Lee Joseph
AU - De Andrade, Mariza
N1 - Funding Information:
This research was supported by grants NIH-CA 77118, NIH-CA 80127, and NIH-CA 84354 from the National Institutes of Health.
PY - 2005/7
Y1 - 2005/7
N2 - 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.
AB - 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.
KW - Chronic obstructive
KW - Leukocyte elastase
KW - Lung neoplasm
KW - Pulmonary disease
KW - Tobacco smoking
KW - α-antitrypsin deficiency
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U2 - 10.1378/chest.128.1.445
DO - 10.1378/chest.128.1.445
M3 - Article
C2 - 16002971
AN - SCOPUS:22244461873
SN - 0012-3692
VL - 128
SP - 445
EP - 452
JO - Chest
JF - Chest
IS - 1
ER -