A new study has shown that individuals with severe alpha-1-antitrypsin deficiency (AATD) and the phenotype PiZZ may be at increased risk of hepatic and nonhepatic cancers compared with the general population.

The study, published in the European Respiratory Journal, found the risk to be increased even after adjusting for age, sex, smoking habits, and liver disease.

“It is well known that individuals with severe AATD, phenotype PiZZ, have an increased risk of developing hepatic cancer,” the authors wrote. “The aim of this study was to evaluate the relative risk and risk factors for incident cancer in the large cohort of PiZZ individuals included in the Swedish AATD Register compared with a random general population sample with known smoking habits, and to evaluate survival after cancer diagnosis.”

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The research team conducted a longitudinal study of 1595 adults with the PiZZ phenotype from the Swedish National AATD registry and 5999 controls with known smoking habits from population-based cohorts in Sweden. The median follow-up time was 17 years. Hepatic and nonhepatic incidence rates per 1000 person-years were calculated, along with adjusted hazard ratios.

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The results revealed an increased risk of developing cancer among patients with severe AATD, even after adjusting for possible risk factors of age, sex, smoking habits, and the presence of liver disease. A significantly higher risk was observed for both ever- and never-smoking patients with the PiZZ phenotype than among matched controls.

Furthermore, survival time after any cancer diagnosis was significantly shorter among PiZZ patients compared with controls, at less than 2 years.

The authors caution that the patients with the PiZZ phenotype included in the study do not represent all PiZZ individuals in Sweden, given that about 25% to 30% of all PiZZ adults are included in the Swedish AATD registry. They recommend early identification and monitoring of patients with severe AATD as well as further studies investigating AATD in the development of cancer.


Hille AM, Ekström M, Piitulainen E, et al. Cancer risk in severe alpha-1-antitrypsin deficiency. Eur Resp J. Published online October 2022. doi:10.1183/13993003.03200-2021