ALPHA-1 antitrypsin genotype, sex, and lung cancer: Clinical and molecular characterisation

INTRODUCTION AND OBJECTIVES: Alpha-1 antitrypsin deficiency is associated with lung and liver disease, but its role in lung carcinogenesis remains unclear. This study aimed to compare the clinical, functional, and molecular characteristics of lung cancer according to alpha-1 antitrypsin (AAT) genotype and, additionally, to explore differences by sex and the possible influence of environmental exposures. PATIENTS AND METHODS: We conducted a cross-sectional, single-centre study including 407 patients with incident lung cancer diagnosed between 2020 and 2023. Clinical, functional, radiological, molecular, and environmental variables were collected. Comparisons were performed between carriers and non-carriers of altered AAT alleles and between women and men. CONCLUSIONS: Patients carrying altered AAT alleles did not exhibit a distinctly different clinical profile, although they showed higher PD-L1 expression (≥50%). Furthermore, significant differences were observed between women and men in terms of exposure, histology and molecular alterations.