The incidence of colorectal cancer (CRC) in individuals younger than 50 years is increasing. 

Dr Elena Stoffel and colleagues ascertained the proportion of young colorectal cancer cases associated with genetic predisposition.

The research team performed a retrospective study of individuals diagnosed with CRC at an age younger than 50 years, evaluated by the clinical genetics service at a single tertiary care cancer center from 1998 through 2015. 

The team collected data on patient histories, tumor phenotypes, and results of germline DNA sequencing. 

For subjects with uninformative clinical evaluations, germline DNA samples were (re)sequenced using a research-based next-generation sequencing multigene panel. 

The team's primary outcome was identification of a pathogenic germline mutation associated with cancer predisposition.

Of 430 young CRC cases, 26% had a first-degree relative with CRC. 

The researchers found that 10% of the subjects with CRC had tumors with histologic evidence for mismatch repair deficiency. 

Of 315 subjects who underwent clinical germline sequencing, 79 had mutations associated with a hereditary cancer syndrome, and 21 had variants of uncertain significance. 

The research team noted that 56 subjects had pathogenic variants associated with Lynch syndrome, and 10 subjects had pathogenic variants associated with familial adenomatous polyposis. 

The team observed that 13 subjects had mutations in other cancer-associated genes, all identified through multigene panel tests. 

Among 117 patients with uninformative clinical evaluations, next-generation sequence analysis using a multigene panel detected actionable germline variants in 5% of patients. 

The research team noted that only 51% of subjects with germline mutations associated with a hereditary cancer syndrome reported a CRC diagnosis in a first-degree relative.

Dr Stoffel's team comments' "Approximately 1 in 5 individuals diagnosed with CRC at age younger than 50 years carries a germline mutation associated with cancer."

"Nearly half of these do not have clinical histories typically associated with the identified syndrome."

"Germline testing with multigene cancer panels should be considered for all young patients with CRC."