Inherited gastric cancer susceptibility

Researcher profiles:

• Professor Parry Guilford
• Chris Hakkaart

Significant genetic risk factors remain unknown

Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome characterised by a very high risk of diffuse-type stomach cancer, and an elevated risk of lobular breast cancer. About 40% of families who meet the clinical criteria (e.g. three or more cases of diffuse gastric cancer in the family) have a germline mutation in the gene CDH1 that encodes the cell-to-cell adhesion protein E-cadherin. However the underlying genetic risk factors for the other 60% of families with HDGC remains unknown.

Higher rate of incidence for Māori

In New Zealand, Māori have rates of gastric cancer three times higher than that of patients of European decent. It is one of the few populations for which diffuse-type is more common than the intestinal-type gastric cancer. Many risk factors have been identified but the reasons behind the increased rates, and more common diffuse type in Māori are not clear.

DNA sequencing to find novel inherited mutations

In this project, we are using next-generation DNA sequencing technology to identify novel inherited mutations in gastric cancer families who do not have germline mutations in CDH1. By finding these mutations we will be able to offer genetic testing to affected families leading to better, more targeted clinical care.

Understanding increased rate will lead to new strategies

By determining the rates, and types of CDH1 mutations in these patients we will provide a better understanding of the increased rate of gastric cancer in Māori. We hope to find an explanation for why diffuse type gastric cancer is so common. This will lead to new strategies in the surveillance, and management of gastric cancer in Māori as well as well as populations worldwide.

Related topics

• Targeting CDH1 deficient cells using synthetic lethal drugs