Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Prophylactic total gastrectomy in hereditary diffuse gastric cancer: identification of two novel CDH1 gene mutations-a clinical observational study

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Risk of multiple colorectal cancer development depends on age and subgroup in individuals with hereditary predisposition

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Unsolicited information letters to increase awareness of Lynch syndrome and familial colorectal cancer: reactions and attitudes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. No evidence of increased breast cancer risk for proven noncarriers from BRCA1 and BRCA2 families

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Detection of PMS2 Mutations by Screening Hereditary Nonpolyposis Colon Cancer Families from Denmark and Sweden

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Answer to: "Is the National Danish Colorectal Cancer Screening Programme a success?"

    Research output: Contribution to journalJournal articleResearch

  3. Evaluation of tumor-infiltrating lymphocytes and association with prognosis in BRCA-mutated breast cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Validation of plasma thyroxine and triiodothyronine methods on the ADVIA Centaur® XP

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. BRCA1 and BRCA2 5' noncoding region variants identified in breast cancer patients alter promoter activity and protein binding

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations
Inactivating mutations in the CDH1 (E-cadherin) gene are the predisposing cause of gastric cancer in most families with hereditary diffuse gastric cancer (HDGC). The lifetime risk of cancer in mutation positive members is more than 80 % and prophylactic total gastrectomy is recommended. Not all mutations in the CDH1 gene are however pathogenic and it is important to classify mutations before this major operation is performed. Probands from two Danish families with gastric cancer and a history suggesting HDGC were screened for CDH1 gene mutations. Two novel CDH1 gene mutations were identified and found pathogenic. In silico and mini-gene assay were used to predict the functional consequence in one of them. Mutation carriers were offered endoscopy and total gastrectomy. The gastric specimens were completely sectioned and examined histologically. Seven asymptomatic mutation carriers were operated. Hospital stay was 6-8 days and there were no complications. Small foci of diffuse gastric cancer were found in all patients-intramucosal in six and advanced in one. Preoperative endoscopic biopsies had revealed a microscopic cancer focus in two of the patients. Our data confirmed the pathogenic nature of both mutations and strongly support the recommendation of total gastrectomy in asymptomatic CDH1 gene mutation carriers. The functional consequences of novel CDH1 gene mutations with uncertain effects should be tested before correct advice and treatment can be given.
Original languageEnglish
JournalFamilial Cancer
Volume13
Pages (from-to)231-42
ISSN1389-9600
DOIs
Publication statusPublished - 4 Jan 2014

ID: 42505160