Alpha-1 Antitrypsin Deficiency and Risk of Lung Cancer in Never-Smokers: A Multicentre Case-Control Study

Abstract

Background Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related death in both sexes worldwide. Although its principal risk factor is smoking habit, there are genetic mutations, such as alpha-1 antitrypsin deficiency (AATD), that have been related with increased risk This study is the continuation of an earlier one published by the same group in 2015, aimed at analysing risk of LC in never-smokers, associated with carriers of the AATD genotype. Methods A multicentre case-control study was conducted in Spain across the period January 2011 to August 2019. Cases were patients with LC, and controls were patients, all never-smokers, undergoing major non-cancer-related surgery. Data were collected on epidemiological characteristics, exposure to environmental tobacco smoke (ETS), residential radon levels, and alpha-1 antitrypsin (AAT) genotype. Results The study included 457 cases (42%) and 631 controls (58%), with a predominance of women. The most frequent histological type was adenocarcinoma (77.5%), followed by squamous cell carcinoma (7.7%). No association of risk of LC was found with the status of AATD genotype carrier, both overall and broken down by age, sex, or exposure to ETS. Conclusions No risk association was found between being a carrier of an AAT deficiency genotype and LC among never-smokers. Even so, new studies are required to provide fuller information in this regard with respect to never-smokers, and possibly even include previous respiratory diseases.