Alpha1-antitrypsin deficiency carriers, tobacco smoke, chronic obstructive pulmonary disease, and lung cancer risk

Ping Yang, Zhifu Sun, Michael J. Krowka, Marie Christine Aubry, William R. Bamlet, Jason A. Wampfler, Stephen N. Thibodeau, Jerry A. Katzmann, Mark S. Allen, David E. Midthun, Randolph S. Marks, Mariza De Andrade

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Background: Genetic susceptibility in lung cancer risk has long been recognized but remains ill defined, as does the role of tobacco smoke exposure and chronic obstructive pulmonary disease (COPD). Methods: Using a dual case-control design, we tested whether alpha1-antitrypsin deficiency (α1ATD) carriers are predisposed to a higher risk of lung cancer, adjusting for the effects of tobacco smoke exposure and COPD. A total of 1856 patients with incident lung cancer were included in the study; 1585 community residents served as controls. A second control group was composed of 902 full siblings of the patients. We first modeled 1585 case-control pairs without the α1ATD variable using multiple logistic regression analysis and then modeled the α1ATD allele type in the presence of other known risk factors of lung cancer. Results: We found a significantly increased lung cancer risk among α1ATDcarriers from 2 parallel case-control comparisons: when patients were compared with unrelated controls, α1ATD carriers had a 70% higher risk of developing lung cancer than noncarriers (odds ratio, 1.7; 95% confidence interval, 1.2-2.4). In a further comparison of patients with their cancer-free siblings, we found a 2-fold increased lung cancer risk in α1ATDcarriers (95% confidence interval, 1.4-2.7). Stratified analysis by tumor histologic subtypes showed a significant increase for adenocarcinoma and squamous cell carcinoma among α1ATD carriers. Conclusion: Our results suggest that α1ATD carriers are at a 70% to 100% increased risk of lung cancer and may account for 11% to 12% of the patients with lung cancer in our study.

Original languageEnglish (US)
Pages (from-to)1097-1103
Number of pages7
JournalArchives of internal medicine
Volume168
Issue number10
DOIs
StatePublished - May 26 2008

ASJC Scopus subject areas

  • Internal Medicine

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