Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori

Autor: Pauline Harawira, Tracey Whaanga, Soo Cheng, Neil Pearce, Lis Ellison-Loschmann, Jonathan Koea, Robert C. Day, Christopher Hakkaart, Andrew Sporle, Parry Guilford, Michelle Gray
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
DNA Mutational Analysis
Disease
030105 genetics & heredity
Germline
CDH1
0302 clinical medicine
Epidemiology
Age of Onset
Genetics (clinical)
Sanger sequencing
Aged
80 and over
biology
Incidence (epidemiology)
Incidence
High-Throughput Nucleotide Sequencing
Middle Aged
Cadherins
030220 oncology & carcinogenesis
symbols
Female
Original Article
Hereditary diffuse gastric cancer
Adult
medicine.medical_specialty
Adolescent
Māori
03 medical and health sciences
symbols.namesake
Young Adult
Antigens
CD
Stomach Neoplasms
Internal medicine
Genetics
medicine
Humans
Genetic Predisposition to Disease
Genetic Testing
Germ-Line Mutation
Aged
Genetic predisposition testing
business.industry
Cancer
E-cadherin
medicine.disease
biology.protein
business
New Zealand
Zdroj: Familial Cancer
ISSN: 1573-7292
1389-9600
Popis: New Zealand Māori have a considerably higher incidence of gastric cancer compared to non-Māori, and are one of the few populations worldwide with a higher prevalence of diffuse-type disease. Pathogenic germline CDH1 mutations are causative of hereditary diffuse gastric cancer, a cancer predisposition syndrome primarily characterised by an extreme lifetime risk of developing diffuse gastric cancer. Pathogenic CDH1 mutations are well described in Māori families in New Zealand. However, the contribution of these mutations to the high incidence of gastric cancer is unknown. We have used next-generation sequencing, Sanger sequencing, and Multiplex Ligation-dependent Probe Amplification to examine germline CDH1 in an unselected series of 94 Māori gastric cancer patients and 200 healthy matched controls. Overall, 18% of all cases, 34% of cases diagnosed with diffuse-type gastric cancer, and 67% of cases diagnosed aged less than 45 years carried pathogenic CDH1 mutations. After adjusting for the effect of screening known HDGC families, we estimate that 6% of all advanced gastric cancers and 13% of all advanced diffuse-type gastric cancers would carry germline CDH1 mutations. Our results demonstrate that germline CDH1 mutations are a significant contributor to the high frequency of diffuse gastric cancer in New Zealand Māori. Electronic supplementary material The online version of this article (10.1007/s10689-018-0080-8) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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