Alpha-1 antitrypsin deficiency associated with increased risks of skin cancer, leukemia, and hepatic cancer: A nationwide cohort study

Background: α₁-Antitrypsin deficiency is characterized by elevated elastase activity and excessive elastin degradation, which may impact cancer development and progression. We tested the hypothesis that individuals with α₁-antitrypsin deficiency have increased susceptibility to cancer in the Danish population. Methods: In a nationwide nested study, we identified 2702 individuals with α₁-antitrypsin deficiency and 26,750 control subjects without α₁-antitrypsin deficiency matched on age, sex, and municipality. We recorded admissions due to cancer as outcomes during a median follow-up of 62 years. Results: Individuals with α₁-antitrypsin deficiency versus control subjects had an increased hazard of skin cancer (2.18, 95%CI: 1.81–2.63), leukemia (1.76, 1.12–2.79), liver cancer (3.91, 2.23–6.85), and cancer overall (1.25, 1.13–1.38). Corresponding hazard ratios when the entire Danish population was used as control group were 3.02 (2.55–3.58), 1.83 (1.19–2.81), 4.46 (2.74–7.28), and 1.45 (1.31–1.59). When the analysis was stratified according to comorbidities, the hazard for skin cancer was higher in those with chronic obstructive pulmonary disease (COPD) (3.59, 2.60–4.95) and skin disease (2.93, 2.19–3.92) but remained elevated in those without any of these diseases. Hazards for skin cancer in individuals with α₁-antitrypsin deficiency were similar when stratified by liver cirrhosis and ischemic heart disease (ps for interaction: ≥0.76). Hazards for liver cancer in individuals with α₁-antitrypsin deficiency versus control subjects were similar when stratified according to liver cirrhosis, COPD, skin disease, and ischemic heart disease (ps for interaction: ≥0.13). Conclusion: Individuals with α₁-antitrypsin deficiency have increased risks of skin cancer, leukemia, and liver cancer in the Danish population.