Cohort-based association study of germline genetic variants with acute and chronic health complications of childhood cancer and its treatment: Genetic Risks for Childhood Cancer Complications Switzerland (GECCOS) study protocol

• Published in: BMJ open Vol. 12; no. 1; p. e052131
• Main Authors: Waespe, Nicolas, Strebel, Sven, Nava, Tiago, Uppugunduri, Chakradhara Rao S, Marino, Denis, Mattiello, Veneranda, Otth, Maria, Gumy-Pause, Fabienne, Von Bueren, André O, Baleydier, Frederic, Mader, Luzius, Spoerri, Adrian, Kuehni, Claudia E, Ansari, Marc
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 24.01.2022; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Protocol
• Subjects: Adult; adverse events; Biobanks; Blood diseases; cancer genetics; Cancer therapies; Cardiomyopathy; Child; Chronic illnesses; clinical pharmacology; Cohort Studies; Cross-Sectional Studies; Dihydrofolate reductase; Genes; Genetic engineering; genetics; Genotype & phenotype; Germ Cells; Hearing loss; Hematology; Humans; Leukemia; Medical diagnosis; Medical research; Metabolism; Multimorbidity; Neoplasms - genetics; Neoplasms - therapy; paediatric clinical genetics & dysmorphology; paediatric oncology; Paediatrics; Patients; Pediatrics; Preventive medicine; Quality of Life; Switzerland; Young Adult; Switzerland; clinical pharmacology; cancer genetics; genetics; paediatric oncology; adverse events; paediatric clinical genetics & dysmorphology
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2021-052131

IntroductionChildhood cancer and its treatment may lead to various health complications. Related impairment in quality of life, excess in deaths and accumulated healthcare costs are relevant. Genetic variations are suggested to contribute to the wide inter-individual variability of complications but have been used only rarely to risk-stratify treatment and follow-up care. This study aims to identify germline genetic variants associated with acute and late complications of childhood cancer.Methods and analysisThe Genetic Risks for Childhood Cancer Complications Switzerland (GECCOS) study is a nationwide cohort study. Eligible are patients and survivors who were diagnosed with childhood cancers or Langerhans cell histiocytosis before age 21 years, were registered in the Swiss Childhood Cancer Registry (SCCR) since 1976 and have consented to the Paediatric Biobank for Research in Haematology and Oncology, Geneva, host of the national Germline DNA Biobank Switzerland for Childhood Cancer and Blood Disorders (BISKIDS).GECCOS uses demographic and clinical data from the SCCR and the associated Swiss Childhood Cancer Survivor Study. Clinical outcome data consists of organ function testing, health conditions diagnosed by physicians, second primary neoplasms and self-reported information from participants. Germline genetic samples and sequencing data are collected in BISKIDS. We will perform association analyses using primarily whole-exome or whole-genome sequencing to identify genetic variants associated with specified health conditions. We will use clustering and machine-learning techniques and assess multiple health conditions in different models.DiscussionGECCOS will improve knowledge of germline genetic variants associated with childhood cancer-associated health conditions and help to further individualise cancer treatment and follow-up care, potentially resulting in improved efficacy and reduced side effects.Ethics and disseminationThe Geneva Cantonal Commission for Research Ethics has approved the GECCOS study.Research findings will be disseminated through national and international conferences, publications in peer-reviewed journals and in lay language online.Trial registration numberNCT04702321.