GENETICS

 
Learning about the risks associated with a CDH1 gene variant (mutation) can be frightening and overwhelming. However, we believe that being proactive and making informed decisions about your health care can be empowering as well as life-saving. Here you will find information, guidance and resources to help you through the genetic counseling and testing process.

E-cadherin is a protein – encoded by the CDH1 gene. This is an image of the structure of the E-cadherin protein chain which bends and turns. The normal function of the E-cadherin protein is to allow cells and tissues to adhere to one another in a normal fashion.

One of the genes in our body is called CDH1. It is located on chromosome 16, and when it is functioning properly it provides instructions for our cells to make the e-cadherin protein, and allows cells to adhere to one another in an orderly manner. A pathogenic variant in this gene interferes with the normal function of the e-cadherin protein and can result in cancer. Another gene, CTNNA1, is found on chromosome 5 and has a similar function to the CDH1 gene.

Hereditary Diffuse Gastric Cancer syndrome (HDGC)  is defined by the presence of a pathogenic germline CDH1 or CTNNA1 variant in an individual with diffuse gastric cancer (DGC) or in a family with one or more DGC cases in first or second degree relatives.

Hereditary Lobular Breast Cancer (HLBC) is defined by the presence of a pathogenic germline CDH1 variant in an individual with lobular breast cancer (LBC) or in a family with one or more LBC cases in first or second degree relatives, having no known DGC in either situation. If someone in an HLBC family is later diagnosed with DGC, the diagnosis is recategorized as HDGC.

Everyone has two copies of the CDH1 gene — one copy inherited from their mother and one copy inherited from their father. If one of these CDH1 genes has a pathogenic variant, this means the person has HDGC (or HLBC). If someone has HDGC or HLBC, each of their offspring has a 50% chance of inheriting the mutated CDH1 gene, and an equal 50% chance of NOT inheriting the mutated CDH1 gene. It is a 50/50 chance per individual, not per all family members. The process is completely random.

Having HDGC does not necessarily mean that a person has or will develop cancer – they may just have a higher risk.