Department of Clinical Biochemistry, Zealand University Hospital, Køge, Denmark.
Department of Clinical Medicine, Faculty of Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Intern Med. 2024 Dec;296(6):460-467. doi: 10.1111/joim.20016. Epub 2024 Oct 1.
α-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 α-antitrypsin deficiency have increased susceptibility to cancer in the Danish population.
In a nationwide nested study, we identified 2702 individuals with α-antitrypsin deficiency and 26,750 control subjects without α-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 α-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 α-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 α-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 α-antitrypsin deficiency have increased risks of skin cancer, leukemia, and liver cancer in the Danish population.
α-抗胰蛋白酶缺乏症的特征是弹性酶活性升高和弹性蛋白过度降解，这可能影响癌症的发生和发展。我们检验了以下假说，即在丹麦人群中，α-抗胰蛋白酶缺乏症患者的癌症易感性增加。
在一项全国性的巢式研究中，我们确定了 2702 名 α-抗胰蛋白酶缺乏症患者和 26750 名无 α-抗胰蛋白酶缺乏症的对照患者，这些对照患者在年龄、性别和市方面与患者相匹配。我们记录了中位随访 62 年期间因癌症导致的住院情况作为结局。
与对照患者相比，α-抗胰蛋白酶缺乏症患者的皮肤癌（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）和癌症总体发病风险（1.25，1.13-1.38）升高。当将整个丹麦人群作为对照组时，相应的危险比为 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）。当根据合并症对分析进行分层时，患有慢性阻塞性肺疾病（COPD）（3.59，2.60-4.95）和皮肤病（2.93，2.19-3.92）的患者皮肤癌风险更高，但在没有这些疾病的患者中风险仍然升高。根据肝硬化和缺血性心脏病分层时，α-抗胰蛋白酶缺乏症患者的皮肤癌风险相似（交互作用 P 值：≥0.76）。与对照组患者相比，α-抗胰蛋白酶缺乏症患者的肝癌风险相似，当根据肝硬化、COPD、皮肤病和缺血性心脏病进行分层时（交互作用 P 值：≥0.13）。
在丹麦人群中，α-抗胰蛋白酶缺乏症患者皮肤癌、白血病和肝癌的风险增加。
