Association of Moderate Alpha-1 Antitrypsin Deficiency with Lung Cancer in the Serbian Population

Abstract

Alpha-1 antitrypsin (AAT) is an important serine protease inhibitor in human plasma. Its major physiological role is to inhibit neutrophil elastase (NE) in the lower respiratory tract and protect lung tissue from destruction. Recent studies indicated an etiological role of NE in lung cancer development. The aim of this study was to investigate the association of alpha-1 antitrypsin deficiency (AATD) with lung cancer in patients with four different histological types of cancer: squamous cell carcinoma, adenocarcinomas, large cell carcinoma and small cell carcinoma. Phenotyping was carried out by isoelectric focusing (pH 4.2-4.9). We compared the frequency of AATD phenotypes in 186 lung cancer patients with the value obtained in our previous study in a healthy Serbian population (3.7%) using the Fisher exact test. Allele frequencies in patients were Pi *M 0.9677, Pi *Z 0.0215, Pi *S 0.0081 and Pi *other rare 0.0027. Eleven of the 186 lung cancer patients (5.9%) were AATD heterozygotes with moderate deficiencies (PiMZ and PiMS). When this value was compared with AATD heterozygote frequency obtained in the healthy individuals (3.7%), the difference was close to the level of significance (p = 0.055). However, individuals with AATD phenotypes had a higher risk of developing squamous cell lung cancer then those with non-deficient AAT variants (OR = 4.51, 95% CI = 1.66-12.29). Our findings provide evidence of an association between AAT phenotypes with moderate deficiency and squamous cell lung cancer.