Germline Cancer Susceptibility Gene Testing in Unselected Patients With Colorectal Adenocarcinoma: A Multicenter Prospective Study

Pedro L.S. Uson, Douglas Riegert-Johnson, Lisa Boardman, John Kisiel, Luke Mountjoy, Neej Patel, Blanca Lizaola-Mayo, Mitesh J. Borad, Daniel Ahn, Mohamad B. Sonbol, Jeremy Jones, Jonathan A. Leighton, Suryakanth Gurudu, Harminder Singh, Margaret Klint, Katie L. Kunze, Michael A. Golafshar, Ed D. Esplin, Robert L. Nussbaum, A. Keith StewartTanio S. Bekaii-Saab, Niloy Jewel Samadder

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background & Aims: Hereditary factors play a role in the development of colorectal cancer (CRC). Identification of germline predisposition can have implications on treatment and cancer prevention. This study aimed to determine the prevalence of pathogenic germline variants (PGVs) in CRC patients using a universal testing approach, association with clinical outcomes, and the uptake of family variant testing. Methods: We performed a prospective multisite study of germline sequencing using a more than 80-gene next-generation sequencing platform among CRC patients (not selected for age or family history) receiving care at Mayo Clinic Cancer Centers between April 1, 2018, and March 31, 2020. Results: Of 361 patients, the median age was 57 years (SD, 12.4 y), 43.5% were female, 82% were white, and 38.2% had stage IV disease. PGVs were found in 15.5% (n = 56) of patients, including 44 in moderate- and high-penetrance cancer susceptibility genes. Thirty-four (9.4%) patients had incremental clinically actionable findings that would not have been detected by practice guideline criteria or a CRC-specific gene panel. Only younger age at diagnosis was associated with the presence of PGVs (odds ratio, 1.99; 95% CI, 1.12–3.56). After a median follow-up period of 20.7 months, no differences in overall survival were seen between those with or without a PGV (P = .2). Eleven percent of patients had modifications in their treatment based on genetic findings. Family cascade testing was low (16%). Conclusions: Universal multigene panel testing in CRC was associated with a modest, but significant, detection of heritable mutations over guideline-based testing. One in 10 patients had changes in their management based on test results. Uptake of cascade family testing was low, which is a concerning observation that warrants further study.

Original languageEnglish (US)
Pages (from-to)e508-e528
JournalClinical Gastroenterology and Hepatology
Issue number3
StatePublished - Mar 2022


  • Colorectal Cancer
  • Germline Testing
  • Homologous Recombination Deficiency
  • Lynch Syndrome

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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