There is no association between carrying the alpha-1 antitrypsin deficiency (AATD) genotype and the risk of lung cancer among people who have never smoked, a new study published in Research Square found.

The AATD genotype has been associated with an increased risk of lung cancer. Here, a team of researchers led by Alberto Ruano-Ravina, PharmD, PhD, from the University of Santiago de Compostela in Spain aimed to investigate this association in people who never smoked.

They collected data about the epidemiological characteristics, exposures to environmental tobacco smoke, residential radon levels, and AAT genotypes of 457 patients with lung cancer and 631 patients who never smoked and underwent major surgery not related to cancer.

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The researchers found no association between lung cancer risk and being a carrier of the AATD genotype. This was the case both overall and when the data was broken down by age, sex, or exposure to environmental tobacco smoke.

“Given that there are no other studies of these characteristics conducted on never-smokers, this could imply that [AATD] may only play a role in carcinogenesis of [lung cancer] in smokers or ex-smokers and may have no influence in the case of never-smokers,” the researcher wrote. 

They speculated that tobacco use could, therefore, act as an effect modifier in carriers of the AATD genotype for the development of lung cancer. More research is needed to provide more information in this matter, the authors said.

AATD can be caused by 1 of 150 different mutations in the SERPINA1 gene. The AAT protein encoded by this gene can be 1 or 4 types: normal, deficient, null, and dysfunctional. 


Tubío-Pérez RA, Torres-Durán M, García-Rodríguez ME, et al. Alpha-1 antitrypsin deficiency and risk of lung cancer in never-smokers: a multicentre case-control study. Research Square. Published online December 6, 2021. doi:10.21203/