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. 2023 Aug 25;14(9):1677.
doi: 10.3390/genes14091677.

Case Series of 11 CDH1 Families (47 Carriers) Including Incidental Findings, Signet Ring Cell Colon Cancer and Review of the Literature

Mathis Lepage  1   2 , Nancy Uhrhammer  1   2 , Maud Privat  1   2 , Flora Ponelle-Chachuat  1   2 , Myriam Kossai  2   3 , Julien Scanzi  4 , Zangbéwendé Guy Ouedraogo  5   6 , Mathilde Gay-Bellile  1   2 , Yannick Bidet  2 , Mathias Cavaillé  1   2
Affiliations

Case Series of 11 CDH1 Families (47 Carriers) Including Incidental Findings, Signet Ring Cell Colon Cancer and Review of the Literature

Mathis Lepage et al. Genes (Basel). .

Abstract

Germline pathogenic variants in E-cadherin (CDH1) confer high risk of developing lobular breast cancer and diffuse gastric cancer (DGC). The cumulative risk of DGC in CDH1 carriers has been recently reassessed (from 40-83% by age 80 to 25-42%) and varies according to the presence and number of gastric cancers in the family. As there is no accurate estimate of the risk of gastric cancer in families without DGC, the International Gastric Cancer Linkage Consortium recommendation is not straightforward: prophylactic gastrectomy or endoscopic surveillance should be proposed for these families. The inclusion of CDH1 in constitutional gene panels for hereditary breast and ovarian cancer and for gastrointestinal cancers, recommended by the French Genetic and Cancer Consortium in 2018 and 2020, leads to the identification of families with lobular cancer without DGC but also to incidental findings of pathogenic variants. Management of CDH1 carriers in case of incidental findings is complex and causes dilemmas for both patients and providers. We report eleven families (47 CDH1 carriers) from our oncogenetic department specialized in breast and ovarian cancer, including four incidental findings. We confirmed that six families did not have diffuse gastric cancer in their medical records. We discuss the management of the risk of diffuse gastric cancer in Hereditary Lobular Breast Cancer (HLBC) through a family of 11 CDH1 carriers where foci were identified in endoscopic surveillance. We also report a new colon signet ring cancer case in a CDH1 carrier, a rare aggressive cancer included in CDH1-related malignancies.

Keywords: CDH1; E-cadherin; HBOC; HDGC; endoscopic finding; incidental finding; prophylactic gastrectomy; signet ring cell carcinoma.

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Conflict of interest statement

The authors declare no conflict of interest.

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