TY - JOUR
T1 - Alpha1-antitrypsin deficiency carriers, tobacco smoke, chronic obstructive pulmonary disease, and lung cancer risk
AU - Yang, Ping
AU - Sun, Zhifu
AU - Krowka, Michael J.
AU - Aubry, Marie Christine
AU - Bamlet, William R.
AU - Wampfler, Jason A.
AU - Thibodeau, Stephen N.
AU - Katzmann, Jerry A.
AU - Allen, Mark S.
AU - Midthun, David E.
AU - Marks, Randolph S.
AU - De Andrade, Mariza
PY - 2008/5/26
Y1 - 2008/5/26
N2 - 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.
AB - 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.
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U2 - 10.1001/archinte.168.10.1097
DO - 10.1001/archinte.168.10.1097
M3 - Article
C2 - 18504338
AN - SCOPUS:44349108422
SN - 2168-6106
VL - 168
SP - 1097
EP - 1103
JO - Archives of internal medicine (Chicago, Ill. : 1908)
JF - Archives of internal medicine (Chicago, Ill. : 1908)
IS - 10
ER -