Germline Cancer Risk Profiles of Young-Onset Colorectal Cancer Patients: Findings from a Prospective Universal Germline Testing and Tele-Genetics Program

Colorectal cancer is being increasingly diagnosed under age 50. An inheritable cancer predisposition has been reported in 22% of the young-onset cases. Assessment of germline risk is critical for personalized cancer care.To implement universal germline cancer risk assessment and testing, and to define the germline cancer risk profiles of patients presenting with young-onset disease.A prospective cohort study.A tertiary-referral academic medical center.Newly diagnosed patients presenting to surgical clinics between September 2019 and February 2021 were treated on a standardized care pathway including universal germline risk assessment.Patients received education material on young-onset disease, genetic testing, and insurance coverage, followed by genetic counseling (either remotely by tele-genetics or in-person). Consenting patients were assessed on a 47-gene common hereditary cancers panel.Proportion of patients with identifiable germline cancer predisposition.Among 500 colorectal cancer patients, 185(37%) were aged 50 or younger (median: 44). A family history was absent in the majority (123, 67%), and 15 tumors (8.1%) were deoxyribonucleic acid mismatch-repair-deficient. Germline testing was completed in 130 patients (70%); the remainder were pending (7%), deceased (1%), or declined (22%). Pathogenic germline mutations were identified in 25 (of 130, 19%) patients: 12 in mismatch repair genes and 13 in other genes. A variant of uncertain significance was found in 23 (18%) patients. Importantly, a pathogenic germline mutation was identified in 12% of the patients without a family history (versus 32% with; p = 0.015) and in 13% of those with mismatch-repair-proficient colorectal cancers (versus 71% if deficient; p0.001).Implemented at single tertiary academic institution.One in five patients with young-onset disease harbored germline cancer predisposition. This detection rate, coupled with a high level of interest and acceptance from patients and feasibility of implementation, support universal germline cancer risk assessment in this patient population. See Video Abstract at http://links.lww.com/DCR/B925.