0
Selected Reports |

α1-Antitrypsin and Neutrophil Elastase Imbalance and Lung Cancer Risk*

Ping Yang, MD, PhD; William R. Bamlet, MS; Zhifu Sun, MD, PhD; Jon O. Ebbert, MD; Marie-Christine Aubry, MD; William R. Taylor, MS; Randolph S. Marks, MD; Claude Deschamps, MD, TS; Stephen J. Swensen, MD; Eric D. Wieben, PhD; Julie M. Cunningham, PhD; Lee Joseph Melton, MD; Mariza de Andrade, PhD
Author and Funding Information

*From the Divisions of Epidemiology and Cancer Center (Drs. Yang, Sun, and Melton), Biostatistics (Mr. Bamlet and Dr. Andrade), Primary Care Internal Medicine (Dr. Ebbert), Anatomic Pathology (Dr. Aubry), Medical Oncology (Dr. Marks), and General Thoracic Surgery (Dr. Deschamps), the Genotyping Share Resource Laboratory (Mr. Taylor and Dr. Cunningham), the Department of Radiology (Dr. Swensen), and the Biochemistry and Molecular Biology and Genomics Research Center (Dr. Wieben), Mayo Clinic College of Medicine, Rochester, MN.

Correspondence to: Ping Yang, MD, PhD, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905; e-mail: yang.ping@mayo.edu



Chest. 2005;128(1):445-452. doi:10.1378/chest.128.1.445
Text Size: A A A
Published online

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.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543