The Inherited and Familial Component of Early-Onset Colorectal Cancer

Early-onset colorectal cancer (EOCRC), defined as that diagnosed before the age of 50, accounts for 10-12% of all new colorectal cancer (CRC) diagnoses. Epidemiological data indicate that EOCRC incidence is increasing, despite the observed heterogeneity among countries. Although the cause for such increase remains obscure, approximate to 13% (range: 9-26%) of EOCRC patients carry pathogenic germline variants in known cancer predisposition genes, including 2.5% of patients with germline pathogenic variants in hereditary cancer genes traditionally not associated with CRC predisposition. Approximately 28% of EOCRC patients have family history of the disease. This article recapitulates current evidence on the inherited syndromes that predispose to EOCRC and its familial component. The evidence gathered support that all patients diagnosed with an EOCRC should be referred to a specialized genetic counseling service and offered somatic and germline pancancer multigene panel testing. The identification of a germline pathogenic variant in a known hereditary cancer gene has relevant implications for the clinical management of the patient and his/her relatives, and it may guide surgical and therapeutic decisions. The relative high prevalence of hereditary cancer syndromes and familial component among EOCRC patients supports further research that helps understand the genetic background, either monogenic or polygenic, behind this increasingly common disease.

Automated summary

Early-onset colorectal cancer (EOCRC), diagnosed before age 50, comprises 10-12% of all new cases and its incidence is increasing. Approximately 13% of EOCRC patients carry pathogenic germline variants in known cancer predisposition genes, including 2.5% with germline pathogenic variants in hereditary cancer genes traditionally not associated with CRC predisposition. The high prevalence of hereditary cancer syndromes and familial history among EOCRC patients supports further research into the genetic background of this common disease.