Advanced adenomas may be a red flag for hereditary cancer syndromes

Swati G Patel; Heather Hampel; Derek Smith; Dexiang Gao; Myles Cockburn; Fay Kastrinos

doi:10.1186/s13053-020-00164-9

Advanced adenomas may be a red flag for hereditary cancer syndromes

Hered Cancer Clin Pract. 2021 Jan 12;19(1):8. doi: 10.1186/s13053-020-00164-9.

Authors

Swati G Patel^{1

2}, Heather Hampel³, Derek Smith⁴, Dexiang Gao⁴, Myles Cockburn^{5

6}, Fay Kastrinos⁷

Affiliations

¹ Department of Internal Medicine, Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, 12631 E 17th Avenue, Room 7614, Campus Box 158, Colorado, Aurora, 80045, USA. Swati.Patel@cuanschutz.edu.
² Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA. Swati.Patel@cuanschutz.edu.
³ Division of Human Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
⁴ Department of Pediatrics, Cancer Center Biostatistics Core, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
⁵ University of Colorado Cancer Center, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA.
⁶ Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
⁷ Division of Gastroenterology & Hepatology, Columbia University Medical Center, New York, NY, USA.

Abstract

Background: 16-25% of colorectal cancers (CRCs) diagnosed under age 50 are associated with hereditary cancer syndromes. Advanced adenomas are considered precursors to CRC. Although polyp removal prevents cancer, polypectomy does not change underlying genetic risk. Patients with isolated advanced polyps do not currently qualify for genetic testing unless they have a personal or family history of cancer.

Aim: Describe the prevalence of hereditary cancer syndromes among patients with advanced colorectal polyps.

Methods: We performed a single center retrospective review from 2015 to 2019 of patients who underwent germline genetic testing with indication for testing listed as colorectal polyp. We excluded patients with a personal history of CRC and those with ≥10 cumulative polyps. We collected patient demographics, polyp characteristics, family history data and genetic testing results from the medical record. Discrete variables were reported as frequency and percentages and continuous variables reported as mean with range.

Results: A total of 42 patients underwent genetic testing due to a personal history of advanced adenoma. 17% of patients met current genetic testing criteria. All patients underwent multi-gene panel testing. Two patients (4.8%) had a germline pathogenic mutation (one in MLH1 and one in CHEK2). The patient with an MLH1 mutation met current criteria for genetic testing (PREMM5 score 5.8), however the patient with the CHEK2 mutation did not. Both mutation carriers had a personal history of synchronous or metachronous advanced adenomas. 38% had a variant of uncertain significance.

Conclusions: 5% of patients with advanced adenomas in our retrospective series had a pathogenic germline mutation in a cancer predisposition gene. Though the patient with a pathogenic mutation in MLH1 met current clinical criteria for genetic testing, this was not recognized prior to referral; he was referred based on a personal history of advanced adenoma. Advanced polyps may be a red flag to identify patients who are at risk for hereditary cancer syndromes.

Keywords: Adenomas; Colorectal cancer; Colorectal polyps; Genetic testing; Lynch syndrome.

Grants and funding

P30CA046934/Foundation for the National Institutes of Health