J Crohns Colitis. 2021 Nov 16;jjab205. doi: 10.1093/ecco-jcc/jjab205. Online ahead of print.

Ohad Atia ¹, Sasha Harel ¹, Natan Ledderman ², Shira Greenfeld ³, Revital Kariv ³, Iris Dotan ⁴, Ran Balicer ⁵, Barbara Silverman ⁶, Eran Matz ⁷, Zohar Levi ⁴, Matti Waterman ⁸, Iris Fried ⁹, Jacob M Rowe ¹⁰, Dan Turner ¹

Author information

¹Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel.

²Meuhedet Health Services, Tel-Aviv, Israel.

³Maccabi Health Services, Tel-Aviv, Israel and the Sackler Faculty of Medicine, Tel Aviv University, Israel.

⁴Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, and the Sackler Faculty of Medicine, Tel Aviv University, Israel.

⁵Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel-Aviv, Israel.

⁶Israel Center for Disease Control, Ministry of Health, Tel Hashomer, Ramat Gan, Israel.

⁷Leumit Health Services, Tel-Aviv, Israel.

⁸Department of Gastroenterology, Rambam Healthcare Campus, Haifa, Israel.

⁹Pediatric Hematology Oncology, Shaare Zedek Medical Center.

¹⁰Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel, and the Technion, Israel Institute of Technology, Haifa, Israel.

Abstract

Background: Pediatric-onset IBD (PIBD) is characterized by a more extensive phenotype than adults and a higher utilization of immunosuppressive medications; both may be associated with malignancy. We aimed to assess the risk of cancer in a nationwide cohort of PIBD and to explore the risks associated with medical treatments.

Methods: PIBD-cases (<18 years) were included from the epi-IIRN cohort, covering 98% of the Israeli population from 2005, linked to the national cancer registry. We matched PIBD cases to non-IBD children for calculating the cumulative incidence of cancer.

Results: 3,944 PIBD cases were included (2,642 [67%] Crohn's disease, 1,302 [33%] ulcerative colitis) translating into 23,635 person-years of follow-up, individually matched to 13,005 non-IBD children. By 30 years of age, 14 IBD patients (0.35%, 5.9/10,000 patient-years) were diagnosed with cancer and one (0.03%) with haemophagocytic-lymphohistiocytosis (HLH), compared with 14 (0.11%, 1.9/10,000 patient-years) cases of cancer (RR 2.5 [95%CI 1.05-6.2]; p=0.04) and no HLH in the comparison-group. There were no cases of hepatosplenic T-cell lymphoma, adenocarcinoma or cholangiocarcinoma. Cancer risk was 15.6 cases/10,000 person-years in those treated with thiopurines alone (RR compared with IBD-patients never exposed to either thiopurines or anti-tumor necrosis factor (TNF) 1.8 (95%CI 0.6-6.1); p=0.2), 11.1/10,000 in those treated with anti-TNF alone (RR 1.3 [95%CI 0.3-6.6]; p=0.5), and 23.1/10,000 treated with combination therapy of anti-TNF and thiopurines (RR 2.8 [95%CI 0.6-13.8]; p=0.2).

Conclusions: PIBD confers an increased risk for malignancy compared with non-IBD children. However, the absolute risk is very low and no differences in risk with specific therapies were apparent in our data.