小儿发作免疫介导的炎症性疾病的癌症风险 - 一项全国研究
The risk of cancer in pediatric-onset immune-mediated inflammatory diseases - A nationwide study
影响因子:7.00000
分区:医学1区 Top / 免疫学1区
发表日期:2024 Dec
作者:
Andrea Ehrström, Sabine Jansson, Marianne Hørby Jørgensen, Vibeke Wewer, Mikkel Malham
摘要
成人发作的免疫介导的炎症性疾病（IMID）增加了几种癌症的风险。但是，有关小儿发作的IMID（PIMID）的数据仍然很少。我们估计了PIMID的长期癌症风险以及医疗与特定癌症之间的关联。我们使用全国丹麦健康登记册来识别从1980年1月1日至2018年12月31日诊断出的PIMID患者。根据年龄，性别和居住，与十名患者相匹配。主要暴露是PIMID，包括自身免疫性肝炎，原发性硬化性胆管炎，克罗恩病，溃疡性结肠炎，青少年特发性关节炎，全身性红斑狼疮，红斑红斑炎，血管炎，血管炎和结缔组织疾病。次要暴露是免疫调节剂和肿瘤坏死因子-α拮抗剂（抗TNFα）。主要结果是癌症。将估计值表示为对诊断时家庭收入调整的危害比率（AHR）。我们包括12,664例PIMID患者和109,274名参考个体。患者的中位随访时间为10.6（四分位间范围：5.4-17.7），参考个体的10.2（四分位间范围：5.2-17.3）年。与参考个体相比，PIMID患者的癌症风险高于癌症风险（AHR 2.2 [95％置信区间（CI）：1.8-2.6]）。硫嘌呤治疗与淋巴瘤的风险更高（AHR 6.1 [95％CI：2.2-16.8]）和皮肤癌（AHR 6.1 [95％CI：2.4-15.4]）。抗TNFα治疗与淋巴瘤的较高风险有关（AHR 4.9 [95％CI：1.1-22.6]）。我们发现，随后PIMID患者癌症的风险增加了。另外，硫嘌呤和抗TNFα与淋巴瘤和皮肤癌风险增加有关。这突出了个性化免疫疗法和癌症监测的重要性。
Abstract
Adult-onset immune-mediated inflammatory disease (IMID) increases the risk of several cancers. However, data on pediatric-onset IMID (pIMID) remains scarce. We estimated the long-term cancer risk in pIMID and the association between medical treatment and specific cancers.We used the nationwide Danish health registers to identify pIMID patients diagnosed from Jan 1, 1980 to Dec 31, 2018. Patients were matched with ten reference individuals based on age, sex, and residence. The primary exposure was pIMID, including autoimmune hepatitis, primary sclerosing cholangitis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, systemic lupus erythematosus, vasculitis, and connective tissue disease. Secondary exposures were immunomodulators and tumor necrosis factor-α antagonists (anti-TNFα). The primary outcome was cancer. Estimates are presented as hazard ratios adjusted for family income at diagnosis (AHR).We included 12,664 pIMID patients and 109,274 reference individuals. Median follow-up time was 10.6 (interquartile range: 5.4-17.7) years for patients and 10.2 (interquartile range: 5.2-17.3) years for reference individuals. Patients with pIMID had a twofold higher cancer risk (AHR 2.2 [95 % confidence interval (CI): 1.8-2.6]) compared with reference individuals. Thiopurine treatment was associated with a higher risk of lymphoma (AHR 6.1 [95%CI: 2.2-16.8]) and skin cancer (AHR 6.1 [95%CI: 2.4-15.4]). Anti-TNFα treatment was associated with a higher risk of lymphoma (AHR 4.9 [95%CI: 1.1-22.6]).We found an increased cancer risk in patients with pIMID followed into adulthood. Additionally, thiopurines and anti-TNFα were associated with increased lymphoma and skin cancer risks. This highlights the importance of individualized immunotherapy and cancer surveillance.