CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: A multicentre study

Patrick R. Benusiglio, David Malka, Etienne Rouleau, Antoine De Pauw, Bruno Buecher, Catherine Noguès, Emmanuelle Fourme, Chrystelle Colas, Florence Coulet, Mathilde Warcoin, Sophie Grandjouan, Alain Sezeur, Pierre Laurent-Puig, Diane Molière, Camille Tlemsani, Marina Di Maria, Veronique Byrde, Suzette Delaloge, Martine Blayau, Olivier Caron

    Research output: Contribution to journalArticlepeer-review

    122 Citations (Scopus)

    Abstract

    Introduction: CDH1 predisposes primarily to diffuse gastric cancer (DGC). Multiple DGC cases in a family, DGC at a young age in an individual or the combination of DGC andlobular breast cancer (LBC) in an individual or a family define the hereditary DGC syndrome (HDGC), and testing for germline CDH1 mutations is warranted in HDGC. Methods and results: We report all index cases from Ile-de-France in which a germline CDH1 mutation has been identified. Out of 18 cases, 7 do not fulfil the HDGC-defining criteria. Three of them are women who presented initially with bilateral LBC below age 50, without personal or family history of DGC, and who subsequently developed symptomatic DGC. Discussion: Our series of CDH1 mutation carriers is the largest to date and demonstrates that LBC might be the first manifestation of HDGC. A personal or family history of multiple LBCs at a young age, even without DGC, should prompt CDH1 mutation screening. It is paramount to identify mutation carriers early, so that they can benefit from prophylactic gastrectomy before they develop symptomatic, highly lethal DGC. We recommend a revision of the HDGC-defining criteria and propose for consideration the name 'Hereditary Diffuse Gastric and Lobular Breast Cancer' instead of HDGC.

    Original languageEnglish
    Pages (from-to)486-489
    Number of pages4
    JournalJournal of Medical Genetics
    Volume50
    Issue number7
    DOIs
    Publication statusPublished - 29 Jul 2013

    Cite this