GTC Biotherapeutics (fka GTCB)

[genisi]

Alpha1-Antitrypsin Deficiency Carriers, Tobacco Smoke, Chronic Obstructive Pulmonary Disease, and Lung Cancer Risk

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

http://archinte.ama-assn.org/cgi/content/short/168/10/1097

Arch Intern Med. 2008;168(10):1097-1103.

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 ({alpha}1ATD) 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}1ATD variable using multiple logistic regression analysis and then modeled the {alpha}1ATD allele type in the presence of other known risk factors of lung cancer.

Results: We found a significantly increased lung cancer risk among {alpha}1ATD carriers from 2 parallel case-control comparisons: when patients were compared with unrelated controls, {alpha}1ATD 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}1ATD 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}1ATD carriers.

Conclusion: Our results suggest that {alpha}1ATD 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.