Genetic predisposition to childhood cancer

Abstract

The etiology of childhood cancer remains largely unknown. Recent evidence suggests that genetic factors play a substantial role in pediatric tumorigenesis. Unlike adult cancers, pediatric cancers typically have a higher prevalence of germline pathogenic variants in cancer predisposition genes. Inherited cancer predisposition syndromes account for approximately 10% of all childhood cancers. Over the years, the diagnosis of cancer predisposition syndromes was based on clinical suspicion prompting referral to a specialized geneticist. However, advances in molecular technologies have led to a shift toward a “genotype-first” approach. Identification of genetic variants related to cancer predisposition enables tailored treatment, improves clinical outcome, optimizes surveillance, and facilitates genetic counseling of the affected child and the family.

Keywords: Cancer; Children; Etiology; Genetics; Cancer predisposition syndromes

Core Tip: Genetic predisposition to childhood cancer has gained increasing attention in recent years as a result of our growing knowledge and advancements in molecular biology. It is estimated that at least 10% of children with cancer have an underlying genetic susceptibility to cancer. Identifying germline pathogenic variants in cancer predisposition genes can be of great importance, both for research studies and clinical implications, including preventive measures, a tailored treatment approach to minimize toxicities, comorbidity evaluation, surveillance and follow-up strategies, comprehensive genetic testing and counseling, psychological support of affected children and their families, and ethical considerations.