儿童免疫介导性炎症性疾病的癌症风险——一项全国性研究

The risk of cancer in pediatric-onset immune-mediated inflammatory diseases - A nationwide study

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JOURNAL OF AUTOIMMUNITY

影响因子:7

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

DOI: 10.1016/j.jaut.2024.103321

摘要

成人发病的免疫介导性炎症性疾病（IMID）会增加多种癌症的风险。然而，有关儿童免疫介导性炎症性疾病（pIMID）的数据仍然稀缺。我们估算了pIMID患者的长期癌症风险及其与特定癌症的关系。我们利用丹麦全国健康登记系统，识别了1980年1月1日至2018年12月31日诊断的pIMID患者。患者与十名对照者（依据年龄、性别和居住地匹配）进行配对。主要暴露因素为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、系统性红斑狼疮、血管炎和结缔组织疾病。次要暴露包括免疫调节剂和肿瘤坏死因子-α拮抗剂（抗-TNFα）。主要结局为癌症。结果以调整家庭收入的风险比（AHR）表示。共纳入12,664名pIMID患者和109,274名对照者。患者的中位随访时间为10.6年（四分位间距：5.4-17.7年），对照组为10.2年（四分位间距：5.2-17.3年）。pIMID患者的癌症风险比对照组高出两倍（AHR 2.2 [95%置信区间（CI）：1.8-2.6]）。硫唑嘌呤治疗与淋巴瘤（AHR 6.1 [95% CI：2.2-16.8]）和皮肤癌（AHR 6.1 [95% CI：2.4-15.4]）的风险增加相关。抗-TNFα治疗亦与淋巴瘤风险增加有关（AHR 4.9 [95% CI：1.1-22.6]）。研究发现，pIMID患者随访至成年后癌症风险增加。此外，硫唑嘌呤和抗-TNFα治疗与淋巴瘤及皮肤癌风险升高有关。这强调了个体化免疫治疗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.