α1-抗胰蛋白酶缺乏的特点是弹性蛋白酶活性升高和弹性蛋白过度降解，这可能会影响癌症的发生和进展。我们测试了丹麦人群中 α1-抗胰蛋白酶缺乏症患者对癌症的易感性增加的假设。在一项全国性巢式研究中，我们确定了 2702 名 α1-抗胰蛋白酶缺乏症患者和 26,750 名没有 α1-抗胰蛋白酶缺乏症的对照受试者，年龄、性别相匹配和市政府。我们在中位随访 62 年期间记录了因癌症入院的结果。与对照受试者相比，α1-抗胰蛋白酶缺乏的个体患皮肤癌（2.18，95%CI：1.81-2.63）、白血病（1.76， 1.12-2.79）、肝癌（3.91、2.23-6.85）和癌症总体（1.25、1.13-1.38）。当整个丹麦人口作为对照组时，相应的风险比分别为3.02（2.55-3.58）、1.83（1.19-2.81）、4.46（2.74-7.28）和1.45（1.31-1.59）。当根据合并症进行分层分析时，患有慢性阻塞性肺病 (COPD) (3.59, 2.60-4.95) 和皮肤病 (2.93, 2.19-3.92) 的人患皮肤癌的风险较高，但在没有任何合并症的人中，皮肤癌的风险仍然较高。这些疾病。按肝硬化和缺血性心脏病分层时，α1-抗胰蛋白酶缺乏症患者患皮肤癌的风险相似（交互作用 ps：≥0.76）。根据肝硬化、慢性阻塞性肺病、皮肤病和缺血性心脏病分层时，α1-抗胰蛋白酶缺乏症个体与对照受试者的肝癌风险相似（交互作用 ps：≥0.13）。α1-抗胰蛋白酶缺乏症个体的风险增加丹麦人口中皮肤癌、白血病和肝癌的发病率。© 2024 作者。约翰·威利出版的《内科杂志》

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.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.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).Individuals with α1-antitrypsin deficiency have increased risks of skin cancer, leukemia, and liver cancer in the Danish population.© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.