Alpha1-antitrypsin deficiency carriers, serum alpha 1-antitrypsin concentration, and non-small cell lung cancer survival

Although the association between alpha 1-antitrypsin deficiency (α₁ATD) carriers and lung cancer risk has been found, the effects of α₁ATD carriers and serum alpha 1-antitrypsin (α₁AT) 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 α₁ATD carrier status tested by isoelectric focusing serum α₁AT concentration by immunonephelometry. The effects of carrier status and serum α ₁AT 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 α₁ATD carriers and 1142 noncarriers. No differences in overall survival by α₁ATD carrier status were found (adjusted hazard ratio [AHR]: 0.98; 95% confidence interval [CI]: 0.82-1.18). Nevertheless, serum α₁AT 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 α₁AT level assessment before any treatment (AHR per 50 mg/dl increments: 1.44; 95% CI: 1.21-1.71). Conclusions: Being an α ₁ATD carrier had no significant effect on NSCLC survival. The increased serum α₁AT concentration was a poor prognosis marker for NSCLC, regardless of carrier status.