Risk of cancer in individuals with severe alpha-1-antitrypsin deficiency (PiZZ) compared with the Swedish general population

Abstract

Background: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ is an established risk factor for chronic obstructive pulmonary disease (COPD) and liver disease, but the risk of developing cancer, other than hepatocellular cancer, is unknown. Our aim was to compare the risk of incident cancer in PiZZ individuals with a random sample from the general population with known smoking habits. Methods: The PiZZ individuals (n=1,585) were included in the Swedish National AATD Register. Controls (n=5,999) were selected from the population-based cohorts within the population-based Obstructive Lung disease in Northern Sweden (OLIN) studies. Data on diagnoses of cancer were obtained by nationwide cross-linkage for AATD individuals and controls with the National Cancer Registry and the Swedish National Patient Register (SNPR). All participants were followed from the date of inclusion in the AATD Register or the OLIN studies (baseline) to the date of first cancer during the follow-up, the date of lung transplantation, the date of death, or study end (January 1st, 2015). Results: During median follow-up of 17 years (range 0.2-23 years), 12% (n=185) of the PiZZ individuals and 10% (n=568) of the controls developed cancer. The risk of incident cancer was significantly higher in the general population than in the PiZZ individuals, adjusted hazard ratio (HR) 1.6 (95% CI 1.3-1.9), also in ever-smokers (HR 1.5; 95% CI 1.2-1.8) and never-smokers (HR 1.7; 95% CI 1.3-2.2). Conclusion: PiZZ individuals have a lower risk of developing incident cancer than the general population adjusting for age and sex, both in ever- and never-smokers.