CDH1 mutation and the link to Hereditary Diffuse Gastric Cancer.

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“Sometimes the bad things that happen in our lives put us directly on the path to the best things that will ever happen to us”.

(From Rachel’s personal blog Cytosine Deleted – Life with the CDH1 genetic mutation).

Rachel Onishi is a pt Health physiotherapist who was recently diagnosed with Hereditary Diffuse Gastric Cancer. Throughout April, pt Health will be working with Rachel to help raise awareness for Hereditary Diffuse Gastric Cancer and the CDH1 gene mutation.

Hereditary Diffuse Gastric Cancer is a rare inherited syndrome that is caused by a genetic mutation in the CDH1 gene.

Chapter 1: CDH1 gene mutation. 

From Rachel’s personal blog.

My husband, my mom, my dad, and I sit around a round table at the hospital waiting for the genetic counsellor to join us.  My husband is playing with a peg game in the room while my mom, dad and I discuss where to eat lunch that day after the appointment.  It’s 11am.   The genetic counsellor joins us at the table.

‘We received the results from your blood test and unfortunately, you tested positive for the CDH1 gene mutation’.

On December 5th, 2013 I had a solid 5 year plan.  On December 6th, everything changed. Missing Cytosine…frameshift mutation…risk of hereditary diffuse gastric cancer.

Rachel received a diagnosis of HDGC two months later.

What is the CDH1 gene mutation?

Much like the well-known BRCA1 or BRCA2 gene mutations, a mutation in the CDH1 gene causes cancer. In the case of CDH1, specifically Hereditary Diffuse Gastric Cancer (HDGC).  The CDH1 gene is located on chromosome 16 and normally encodes for a protein called E-cadherin. This protein allows cells and tissues to adhere to one another.

When there is a mutation, the function of the E-cadherin protein is disrupted, often resulting in cancer. However, the exact way in which this mutation ultimately causes gastric cancer is not entirely known. The CDH1 mutation was discovered in 1998.


E-Cadherin Protein

E-Cadherin Protein

How is it inherited?

Inheritance of the CDH1 gene mutation follows an autosomal dominant pattern, meaning that offspring of mutation carriers have a 50% chance of inheriting the mutant gene. An estimated three out of every four CDH1 gene mutation carriers will go on to develop gastric cancer, with an average age at diagnosis of 38.

In Rachel’s case, she got her diagnosis at the age of 29. Her grandfather died of HDGC kind of cancer at the age of 30.

However, not all HDGC families have a mutation in the CDH1 gene.

Who should be tested?

A lot has to do with family history. Typically, families with HDGC have a very distinct pattern of cancers. There are often several individuals over several generations diagnosed with diffuse-type gastric cancer. Often, the diagnosis is made at younger ages – often less than 50 years old. There might also be a presence of colorectal cancer or lobular breast cancer in the family.

From the Zane Cohen Centre at Mount Sinai in Toronto:

“Eligible families who have at least two relatives with diffuse-type gastric cancer, at least one diagnosed under age 50, or families with at least three relatives with diffuse-type gastric cancer at any age. Families with once case of very young diffuse-type gastric cancer (e.g. under age 35), or families with diffuse-type gastric cancer and lobular breast cancer may also be considered.”

How did Rachel’s family find out?

There was a significant pattern in Rachel’s family of stomach cancer and breast cancer. As mentioned previously, her grandfather had died of HDGC at the age of 30. Rachel’s mother found out from a cousin about the gene. Prior to that, Rachel’s family didn’t know about it. Rachel’s mother was tested in September of 2009 and had a gastroectmy (complete stomach removal) in March of 2010.

Next post – testing and diagnosis for HDGC.

“Then the news came.  We found two areas of carcinoma in your stomach.  One in the proximal fundus stomach of the stomach and one at the gastroesophageal junction of the stomach side.” 



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