The objectives of the GECCOS project are to identify genetic variants associated with complications of childhood cancer using genotype-phenotype association studies. Germline genetic samples and data of the "Germline DNA Biobank for Childhood Cancer and Blood Disorders Switzerland" (BISKIDS) which is included in the Geneva Biobank for Hematology and Oncology in Pediatrics (BaHOP) will be used with clinical data of Swiss childhood cancer patients collected at the Institute of Social and Preventive Medicine in Bern.

Background and rationale :

Around 300 children and adolescents are diagnosed with cancer each year in Switzerland. A wide range of acute and chronic complications have been linked to cancer and its treatments. Cancer treatments, though highly curative, have a high incidence of adverse events, not only acutely but also chronically. Depending on the type and dose of treatments, the complications vary. There are important inter-individual differences in the type and severity of complications associated with similar cancer treatments. Genetic variation was identified to affect some complications and is suspected to play an important role in many of these differences.

The GECCOS project on analysis of genetic risks for complications associated with childhood cancers fills the gap to analyze germline genetic data with clinical information on short- and long-term complications. This has not been done on a nationwide scale in Switzerland yet. The GECCOS project will improve knowledge on germline genetic risks for complications and further personalize care during acute treatment and follow-up of childhood cancer patients.

Objectives:

Primary objectives:

1. Identify genetic variants associated with complications after childhood cancer leading to specific organ dysfunctions and second primary neoplasms.
2. Evaluate the functional importance of genetic variants for complications after childhood cancer through in silico and in vitro studies.

Secondary objective:

Assess genetic variants and their impact on multiple outcomes as a result of specific treatment exposures.

Inclusion Criteria:

1. Registered in the Swiss Childhood Cancer Registry (SCCR) since 1976; AND
2. consented to the BaHOP (host biobank for the BISKIDS Biobanking project); AND
3. diagnosed with cancer according to the International Classification of Childhood Cancer, version 3, ICCC-3, or Langerhans cell histiocytosis (LCH) before age 21 years.

Exclusion Criteria:

1. Lacking written consent signed by participant and/ or their legal representative to participate in the BaHOP (where applicable); OR
2. died after study participation and declined use of their samples and data after their death in the original consent for BaHOP (as indicated on the BaHOP consent).

Brief description of the anticipated study population:

Swiss childhood cancer patients and survivors are being invited to participate in the BaHOP biobank hosting the Germline DNA Biobank for Childhood Cancer and Blood Disorders Switzerland (BISKIDS). Recruitment for BISKIDS is done by the collaborators at the Institute of Social and Preventive Medicine (ISPM), University of Bern. As of December 2019, 9,306 persons were alive and eligible to participate in this project. Participants are invited in batches depending on inclusion criteria of specific sub-projects. Clinical data is collected at the ISPM for childhood cancer patients and survivors since 1976 which will be available for the GECCOS project for genotype-phenotype analysis.

Upon specific request to study PI (Marc.Ansari@hcuge.ch or: biskids@cansearch.ch)