Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr;21(2):235-239.
doi: 10.1007/s10689-021-00257-x. Epub 2021 Apr 22.

CDH1 pathogenic variants and cancer risk in an unselected patient population

Ariel Bar-Mashiah #  1 , Emily R Soper #  2   3 , Sinead Cullina  2   4 , Gillian M Belbin  2   5 , Eimear E Kenny  2   4   5 , Aimee L Lucas  6 , Noura S Abul-Husn  7   8   9   10
Affiliations

CDH1 pathogenic variants and cancer risk in an unselected patient population

Ariel Bar-Mashiah et al. Fam Cancer. 2022 Apr.

Abstract

CDH1 pathogenic variants confer a markedly elevated lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). The aim of this study was to evaluate the prevalence and clinical impact of CDH1 pathogenic variants in the unselected and ancestrally diverse BioMe Biobank. We evaluated exome sequence data from 30,223 adult BioMe participants to identify CDH1 positive individuals, defined as those harboring a variant previously classified as pathogenic or likely pathogenic or a predicted loss-of-function variant in CDH1. We reviewed electronic health records and BioMe enrollment surveys for personal and family history of malignancy and evidence of prior clinical genetic testing. Using a genomics-first approach, we identified 6 CDH1 positive individuals in BioMe (~ 1 in 5000). CDH1 positive individuals had a median age of 42 years (range 35-62 years), all were non-European by self-report, and one was female. None had evidence of either a personal or family history of DGC or LBC. Our findings suggest a low risk of DGC and LBC in unselected patients harboring a pathogenic variant in CDH1. Knowledge of CDH1-related cancer risk in individuals with no personal or family history may better inform surveillance and prophylactic measures.

Keywords: CDH1; Diffuse gastric cancer; Genomic risk; Hereditary diffuse gastric cancer.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest/Competing interests: Dr. Abul-Husn was previously employed by Regeneron Pharmaceuticals and has received a speaker honorarium from Genentech. E.E.K has received speaker honoraria from Illumina and Regeneron Pharmaceuticals. The remaining authors have no relevant financial or non-financial interests to disclose.

References

    1. Blair VR, et al., Hereditary diffuse gastric cancer: updated clinical practice guidelines. The Lancet Oncology, 2020. 21(8): p. e386–e397. - PMC - PubMed
    1. van der Post RS, et al., Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet, 2015. 52(6): p. 361–74. - PMC - PubMed
    1. Caldas C, et al., Familial gastric cancer: overview and guidelines for management. J Med Genet, 1999. 36(12): p. 873–80. - PMC - PubMed
    1. Katona BW, Clark DF, and Domchek SM, CDH1 on Multigene Panel Testing: Look Before You Leap. J Natl Cancer Inst, 2020. 112(4): p. 330–334. - PMC - PubMed
    1. Roberts ME, et al., Comparison of CDH1 Penetrance Estimates in Clinically Ascertained Families vs Families Ascertained for Multiple Gastric Cancers. JAMA Oncol, 2019. - PMC - PubMed

Publication types