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儿童期起病的免疫介导性炎症性疾病中的癌症风险——一项全国性研究。

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

作者信息

Ehrström Andrea, Jansson Sabine, Jørgensen Marianne Hørby, Wewer Vibeke, Malham Mikkel

机构信息

Department of Pediatric and Adolescent Medicine, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.

Department of Pediatric and Adolescent Medicine, Copenhagen University Hospital -Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

J Autoimmun. 2024 Dec;149:103321. doi: 10.1016/j.jaut.2024.103321. Epub 2024 Sep 26.

Abstract

BACKGROUND AND OBJECTIVES

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.

METHODS

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).

RESULTS

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]).

CONCLUSIONS

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.

摘要

背景与目的

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,关于儿童发病的IMID(pIMID)的数据仍然稀少。我们估计了pIMID患者的长期癌症风险以及药物治疗与特定癌症之间的关联。

方法

我们使用丹麦全国性健康登记系统来识别1980年1月1日至2018年12月31日期间确诊的pIMID患者。根据年龄、性别和居住地,将患者与十名对照个体进行匹配。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、幼年特发性关节炎、系统性红斑狼疮、血管炎和结缔组织病。次要暴露因素为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。估计值以诊断时家庭收入调整后的风险比(AHR)表示。

结果

我们纳入了12,664例pIMID患者和109,274名对照个体。患者的中位随访时间为10.6(四分位间距:5.4 - 17.7)年,对照个体为10.2(四分位间距:5.2 - 17.3)年。与对照个体相比,pIMID患者的癌症风险高出两倍(AHR 2.2 [95%置信区间(CI):1.8 - 2.6])。硫嘌呤治疗与淋巴瘤(AHR 6.1 [95%CI:2.2 - 16.8])和皮肤癌(AHR 6.1 [95%CI:2.4 - 15.4])的较高风险相关。抗TNFα治疗与淋巴瘤(AHR 4.9 [95%CI:1.1 - 22.6])的较高风险相关。

结论

我们发现随访至成年期的pIMID患者癌症风险增加。此外,硫嘌呤和抗TNFα与淋巴瘤和皮肤癌风险增加相关。这凸显了个体化免疫治疗和癌症监测的重要性。

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