DOI: 10.1136/bmjopen-2026-120576 ISSN: 2044-6055

Childhood cancer predisposition study: a prospective registry and biorepository protocol

Melissa R Perrino, Suzanne P MacFarland, Luke Maese, Jennie Vagher, Junne Kamihara, Surya Rednam, Philip J Lupo, Garrett M Brodeur, Joshua Schiffman, Lisa Diller, Lauren Desrosiers-Battu, Sharon E Plon, Kim E Nichols, Samuel L Volchenboum, David Malkin, Anita Villani, Christopher C Porter
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Introduction

Cancer is the most common cause of disease-related mortality in children, highlighting the urgent need for improved care in this population. It is estimated that >15% of children diagnosed with cancer harbour a germline pathogenic variant in a cancer predisposition gene which confers an increased risk to develop cancer. There are over 100 genes associated with cancer predisposition syndromes (CPSs) and greater availability and acceptability of genetic testing in the last decade has facilitated their recognition in childhood. However, individually, each of these CPSs is rare, impeding robust research and advancement of clinical care. Once a specific CPS is diagnosed, current recommendations for clinical care are based primarily on expert consensus with a ’one size fits all’ approach to management. Detailed knowledge of genotype-phenotype associations and the impact of genetic modifiers is lacking, and due to strong ascertainment bias of children already diagnosed with cancer predominantly being tested for a CPS, the true cancer risk is likely overestimated.

Methods and analyses

The Childhood Cancer Predisposition Study (CCPS) is a multi-centre registry and biorepository for children and adolescents aged 0–21 years with a clinical or molecularly confirmed CPS and their family members ( NCT04511806 ). The study objectives are to characterise the natural history of each CPS, correlate the natural history phenotype with CPS genotype, evaluate the efficacy of standard surveillance strategies and allow future investigation into the feasibility and effectiveness of novel surveillance strategies. The principal study question is whether adherence to recommended tumour surveillance guidelines is associated with earlier detection of tumours and/or improved survival. We will also address what barriers exist that prevent adherence to surveillance guidelines. Data collected from primary subjects includes detail about the CPS, genomic data, cancer history and family cancer history, as well as information about tumour surveillance. Required biospecimen collection includes germline DNA samples, with optional collection of serial blood and stool samples. Planned enrolment is 1050 primary subjects.

Ethics and dissemination

CCPS was reviewed and approved by a central IRB (WCG IRB 2020P002450) and the Research Ethics Board at The Hospital for Sick Children in Toronto (1000072286). Written informed consent is obtained from all participants. Data and specimens are available to qualified investigators by request to address specific research questions through a standardised research application process. In addition, de-identified data are available through the Pediatric Cancer Data Commons for exploration. Analysed data will be disseminated in peer-reviewed publications and at conferences including meetings inclusive of patient and family advocacy groups.

Trial registration number

NCT04511806 .

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