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Bar-Mashiah A, Soper ER, Cullina S, et al. CDH1 pathogenic variants and cancer risk in an unselected patient population. Fam Cancer. 2021;doi: 10.1007/s10689-021-00257-x.
Bar-Mashiah, A., Soper, E. R., Cullina, S., Belbin, G. M., Kenny, E. E., Lucas, A. L., & Abul-Husn, N. S. (2021). CDH1 pathogenic variants and cancer risk in an unselected patient population. Familial cancer, . https://doi.org/10.1007/s10689-021-00257-x
Bar-Mashiah, Ariel, et al. "CDH1 pathogenic variants and cancer risk in an unselected patient population." Familial cancer vol. (2021). doi: https://doi.org/10.1007/s10689-021-00257-x
Bar-Mashiah A, Soper ER, Cullina S, Belbin GM, Kenny EE, Lucas AL, Abul-Husn NS. CDH1 pathogenic variants and cancer risk in an unselected patient population. Fam Cancer. 2021 Apr 22; doi: 10.1007/s10689-021-00257-x. Epub 2021 Apr 22. PMID: 33886068; PMCID: PMC8531152.
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Fam Cancer. 2021 Apr 22; doi: 10.1007/s10689-021-00257-x. Epub 2021 Apr 22.

CDH1 pathogenic variants and cancer risk in an unselected patient population.

Familial cancer

Ariel Bar-Mashiah, Emily R Soper, Sinead Cullina, Gillian M Belbin, Eimear E Kenny, Aimee L Lucas, Noura S Abul-Husn

Affiliations

  1. Icahn School of Medicine At Mount Sinai, New York, NY, USA.
  2. The Institute for Genomic Health, Icahn School of Medicine At Mount Sinai, One Gustave L. Levy Place, Box 1003, New York, 10029, NY, USA.
  3. Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine At Mount Sinai, New York, NY, USA.
  4. Department of Genetics and Genomic Sciences, Icahn School of Medicine At Mount Sinai, New York, NY, USA.
  5. Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine At Mount Sinai, New York, NY, USA.
  6. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine At Mount Sinai, New York, NY, USA.
  7. The Institute for Genomic Health, Icahn School of Medicine At Mount Sinai, One Gustave L. Levy Place, Box 1003, New York, 10029, NY, USA. [email protected].
  8. Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine At Mount Sinai, New York, NY, USA. [email protected].
  9. Department of Genetics and Genomic Sciences, Icahn School of Medicine At Mount Sinai, New York, NY, USA. [email protected].
  10. Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine At Mount Sinai, New York, NY, USA. [email protected].

PMID: 33886068 PMCID: PMC8531152 DOI: 10.1007/s10689-021-00257-x

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

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