Genetic Risks for Childhood Cancer Complications in Switzerland

University Hospital, Geneva6,000 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

6,000

Conditions

Childhood Cancer

Eligibility

Sex: ALLMax age: 21 Years

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

Genetic variants in participants as a possible marker of risk of complications after childhood cancer

Genotyping of germline genetic variants (candidate gene, whole exome, or whole genome sequencing data)

Time frame: Genetic sequencing performed at enrollment into study

Secondary Outcomes

Number of participants with complications of childhood cancers: specific organ dysfunctions assessed by objective measurements and second primary neoplasms, extracted from medical records and cancer registry information

* Specific organ dysfunctions assessed by objective measurements, e.g. audiograms for hearing loss, and self-assessment with questionnaires and * Second primary neoplasms as defined by the International Agency for Research on Cancer (IARC) criteria

Time frame: Data collection at enrollment into study, and longitudinal data collection until last follow-up or death from any cause, approx. 10 years

Demographic and clinical covariates corresponding to possible risk factors for specific complications after childhood cancer, extracted from medical records and cancer registry information

Covariates include but are not restricted to the collection of the following data: * demographic information, e.g. sex, age and year at diagnosis, etc. * cancer-related information, e.g. cancer type, stage, metastases, etc. * treatment-related risk factors, e.g. platinum chemotherapy exposure (with cumulative dose, mg/m2) for hearing impairment, radiation dose (gray) and fields for radiation toxicity, etc.