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Arch Intern Med. 2008 May 26;168(10):1097-103. doi: 10.1001/archinte.168.10.1097.

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

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Division of Epidemiology and Cancer Center, Mayo Clinic, Rochester, Minnesota 55905, USA.



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).


Using a dual case-control design, we tested whether alpha(1)-antitrypsin deficiency (alpha(1)ATD) 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 alpha(1)ATD variable using multiple logistic regression analysis and then modeled the alpha(1)ATD allele type in the presence of other known risk factors of lung cancer.


We found a significantly increased lung cancer risk among alpha(1)ATD carriers from 2 parallel case-control comparisons: when patients were compared with unrelated controls, alpha(1)ATD 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 alpha(1)ATD carriers (95% confidence interval, 1.4-2.7). Stratified analysis by tumor histologic subtypes showed a significant increase for adenocarcinoma and squamous cell carcinoma among alpha(1)ATD carriers.


Our results suggest that alpha(1)ATD 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.

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