Alpha‑1 antitrypsin deficiency and risk of lung cancer in never‑smokers: A multicentre case–control study

Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related death in both sexes worldwide. Although the principal risk factor in the western world is tobacco smoking, genetic factors, including alpha-1 antitrypsin deficiency (AATD), have been associated with increased risk.
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Alpha‑1 antitrypsin deficiency and risk of lung cancer in never‑smokers: A multicentre case–control studyTubío‑Pérezetal. BMC Cancer (2022) 22:81https://doi.org/10.1186/s12885-022-09190-3 RESEARCH Open AccessAlpha‑1 antitrypsin deficiency andriskoflung cancer innever‑smokers: amulticentrecase–control studyRamónAntonioTubío‑Pérez1, MaríaTorres‑Durán1*, MaríaEsmeraldaGarcía‑Rodríguez1,CristinaCandal‑Pedreira2, JuliaRey‑Brandariz2, MónicaPérez‑Ríos3, JuanBarros‑Dios3,AlbertoFernández‑Villar1and AlbertoRuano‑Raviña3  Abstract  Background:  Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related death in both sexes worldwide. Although the principal risk factor in the western world is tobacco smoking, genetic factors, including alpha-1 antitrypsin deficiency (AATD), have been associated 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 non-smokers diagnosed with LC, and controls were composed of never-smoking individuals 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 (72,8%). The most frequent histological type was adenocarcinoma (77.5%), followed by squamous cell carcinoma (7.7%). No asso‑ ciation 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. In order to establish the existence of an association, we consider it important to expand the studies in never smokers in different geographical areas as well as to include patients with previous chronic lung diseases to assess if it influences the risk. Keyword:  Alpha-1 antitrypsin, lung cancer, never-smokersBackground 5-year survival rate of 13–20% [3]. Tobacco smoking isLung cancer (LC) is the most commonly diagnosed can- its principal risk factor, followed by exposure to radon,cer and the leading cause of cancer-related death in both which is the second leading LC risk factor globally, andsexes worldwide [1, 2]. Currently it has an estimated the leading LC risk factor among never-smokers [4]. LC among never-smokers has increased in incidence,*Correspondence: maria.luisa.torres.duran@sergas.es accounting for 15% of all lung cancers in the USA in1 Pulmonary Department, Hospital Álvaro Cunqueiro, ASVigo; recent years [5]. It displays characteristics that distin-NeumoVigo I+I Research Group, Galicia Sur Health Research Institute guish it from LC in smokers, including a number of(IISGS), Galicia, SpainFull list of author information is available at the end of the article genes [6] and their protein products, which could act © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission dir ...