Alpha1-Antitrypsin Deficiency Carriers, Serum Alpha 1-Antitrypsin Concentration, and Non-small Cell Lung Cancer Survival

Introduction: Although the association between alpha 1-antitrypsin deficiency (alpha(1)ATD) carriers and lung cancer risk has been found, the effects of alpha(1)ATD carriers and serum alpha 1-antitrypsin (alpha(1)AT) concentration on non-small cell lung cancer (NSCLC) survival remained unclear. Methods: Patients were selected from the Epidemiology and Genetics of Lung Cancer Study at Mayo Clinic with the criteria of (1) primary NSCLC diagnosis and (2) available alpha(1)ATD carrier status tested by isoelectric focusing serum alpha(1)AT concentration by immunonephelometry. The effects of carrier status and serum alpha(1)AT concentration on survival were evaluated by Cox proportional hazards models with (1) a landmark approach, where overall survival was defined from the time of blood draw to death from any cause and (2) included only patients with blood draw time before initial treatment. Results: One thousand three hundred twenty-one patients were included in this study, with 179 alpha(1)ATD carriers and 1142 noncarriers. No differences in overall survival by alpha(1)ATD carrier status were found (adjusted hazard ratio [AHR]: 0.98; 95% confidence interval [CI]: 0.82-1.18). Nevertheless, serum alpha(1)AT concentration was significantly associated with survival among all patients in the landmark model (AHR per 50 mg/dl increments: 1.15; 95% CI: 1.10-1.20) and among patients whose blood was drawn for serum alpha(1)AT level assessment before any treatment (AHR per 50 mg/dl increments: 1.44; 95% CI: 1.21-1.71). Conclusions: Being an alpha(1)ATD carrier had no significant effect on NSCLC survival. The increased serum alpha(1)AT concentration was a poor prognosis marker for NSCLC, regardless of carrier status.