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

Adenocarcinoma / diagnosis Colorectal Neoplasms / diagnosis Female Genetic Predisposition to Disease Genetic Testing / methods Germ Cells Humans Middle Aged Prospective Studies

Colorectal Cancer Germline Testing Homologous Recombination Deficiency Lynch Syndrome

Journal

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

ISSN: 1542-7714

Titre abrégé: Clin Gastroenterol Hepatol

Pays: United States

ID NLM: 101160775

Informations de publication

Date de publication:
03 2022

Historique:

received: 21 11 2020

revised: 03 04 2021

accepted: 06 04 2021

pubmed: 16 4 2021

medline: 17 3 2022

entrez: 15 4 2021

Statut: ppublish

Résumé

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. 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. 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%). 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.

Sections du résumé

BACKGROUND & AIMS

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.

Identifiants

DOI: 10.1016/j.cgh.2021.04.013 PMID: 33857637

pubmed: 33857637

pii: S1542-3565(21)00447-X

doi: 10.1016/j.cgh.2021.04.013

pii:

doi:

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

e508-e528

Commentaires et corrections

Type : CommentIn