α-1抗胰蛋白酶缺乏症与皮肤癌、白血病和肝癌风险增加相关：一项全国队列研究

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

JOURNAL OF INTERNAL MEDICINE

影响因子:9.2

分区:医学1区 Top / 医学：内科2区

发表日期:2024 Dec

作者: Nanna J Korsbæk, Eskild M Landt, Sarah C W Marott, Børge G Nordestgaard, Gabrielle R Vinding, Gregor B E Jemec, Morten Dahl

DOI: 10.1111/joim.20016

摘要

α-1抗胰蛋白酶缺乏症表现为弹性蛋白酶活性升高及弹性蛋白过度降解，可能影响癌症的发生和发展。本研究假设在丹麦人群中，α-1抗胰蛋白酶缺乏症患者更易罹患癌症。通过全国性嵌套队列研究，识别出2702例α-1抗胰蛋白酶缺乏症患者及26,750名匹配的对照（按年龄、性别、行政区划匹配），在中位随访62年期间记录癌症相关住院病例。结果显示，α-1抗胰蛋白酶缺乏症患者相较于对照组，皮肤癌风险增加（HR=2.18，95%CI：1.81-2.63）、白血病（HR=1.76，1.12-2.79）、肝癌（HR=3.91，2.23-6.85）及总体癌症（HR=1.25，1.13-1.38）。当以整个丹麦人口作为对照时，风险比为：皮肤癌3.02（2.55-3.58）、白血病1.83（1.19-2.81）、肝癌4.46（2.74-7.28）及总体癌症1.45（1.31-1.59）。根据合并症状态分层分析，慢性阻塞性肺疾病（COPD）患者皮肤癌风险更高（HR=3.59，2.60-4.95），皮肤疾病患者亦升高（HR=2.93，2.19-3.92），但在无相关疾病者中仍显著升高。按肝硬化和缺血性心脏病分层，α-1抗胰蛋白酶缺乏症患者的皮肤癌风险无显著差异（交互作用p≥0.76），肝癌风险在不同分层中亦无显著差异（p≥0.13）。综上，α-1抗胰蛋白酶缺乏症患者在丹麦人群中存在皮肤癌、白血病和肝癌的风险升高。

Abstract

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.