CDH1 gene mutation causes stomach cancer: How is it inherited?

CDH1 Mutations and Inheritance

By Amy Stettner, MS, CGC
Genetic Counselor
Madison, WI

Our bodies are made up of trillions of tiny cells. We have skin cells, muscle cells, bone cells, stomach cells, etc. Each cell contains a copy of our genetic code. This genetic code is made up of DNA and is packaged into structures called chromosomes. Although our DNA is extremely important, it is actually a very simple chemical, made up of only 4 different subunits abbreviated A, T, G, and C. (A = adenine, T = thymine, G = guanine, and C = cytosine.) There are about 4 billion A’s, T’s, G’s, and C’s in our genetic code. A gene is a segment of DNA with a very specific order of A’s, T’s, G’s, and C’s. This order of chemicals is called a gene’s “sequence”. Humans have about 30,000 different genes in their cells. Each gene provides the cells with instructions to make a specific product that the body needs to work properly. If there is an error (ie, a mutation) in a gene’s sequence, then the gene cannot provide the correct message for the body, the gene’s product won’t be made correctly, and the body might be missing an important product. Depending on the gene, there might be small or serious consequences.

One gene in our body is called CDH1. When this gene has the correct sequence of A’s, T’s, G’s, and C’s it provides the instruction for the cell to make the e-cadherin protein. Hereditary diffuse gastric cancer is caused by an inherited error (mutation) in the CDH1 gene. This mutation prevents the correct production of the e-cadherin protein.

Everyone has two copies of the CDH1 gene — a copy they inherited from their mother and a copy they inherited from their father. If one of these CDH1 genes has a mutation, then the person has hereditary diffuse cancer syndrome. If someone has hereditary diffuse gastric cancer syndrome, then each child he or she has will have a 50% chance of inheriting the CDH1 mutation (and therefore hereditary diffuse gastric cancer syndrome) and an equal 50% chance of NOT having inherited the mutation (and therefore NOT having hereditary diffuse gastric cancer syndrome).

To understand this more easily, consider the following picture. This image shows the complete set of chromosomes taken from a single human cell. The picture has been magnified many times and the chromosomes have been neatly arranged. Humans have 46 chromosomes in their cells and these 46 chromosomes come in 23 pairs. The first 22 pairs of chromosomes are basically arranged by size, with pair 1 being the largest and pairs 22 and 23 being the smallest. The last pair of chromosomes are called the sex chromosomes – women have two X chromosomes while men have 1 X and 1 Y (as shown). Our 30,000 different genes are spread among these 23 pairs of chromosomes. The CDH1 gene is located on chromosome 16. Because we have two copies of chromosome 16, we have two copies of the CDH1 gene.


A person with Hereditary Diffuse Gastric Cancer syndrome has an inherited mutation in one of their CDH1 genes.

When this person has a child, he will pass on only half of his chromosomes. He will pass on one chromosome from each of his 23 pairs and the child’s mother will do the same. So this gentleman will pass on either the copy of chromosome 16 with the CDH1 mutation or the copy of chromosome 16 that does NOT carry the CDH1 mutation. This process is completely random and that’s why anyone who has a CDH1 mutation has a 50% chance of passing that mutation on to a child. This 50% risk applies separately to each pregnancy. (Note that this example showed a male with a CDH1 mutation. The inheritance situation is exactly the same for a woman with a CDH1 mutation.)

7 Responses to CDH1 gene mutation causes stomach cancer: How is it inherited?

  1. Reena says:

    Hi!my husbands grandfather had colon cancer at the age of 60 or 65,now my husband’s father has gastric cancer at the age of 55 ,my husband is the eldest son n has a younger brother too ,now I want to know does both have the risk of cancer and how many percent.thank you very concerned .

    • karen says:

      Reena, being proactive about your family heath risks is very important – so it is good that you’re asking these questions. Talking to a genetic counselor about your concerns is a good place to begin. They will help to determine if your family is at risk for HDGC or any other familial and iniherited cancer risks. Visit our Gastric Cancer page for a link to help you find a genetic counselor in your area. Also, share the No Stomach For Cancer website link with your family physician, genetic counselor and other medical professionals that you work with.

      I hope this helps.

      Best regards.

  2. Mary Pepitone says:

    My grandfather had passed from stomach cancer as well as my mother.
    Please explain to me, as I read, the cancer can go from 100% from my grandfather
    to 50% for my mother and may pass half of her 50% to me (which is 25%)?
    Or do we get half the CDHI gene and its a toss up for the good or bad one with each
    generation?? I am a little confused on this.
    Also, is it ever possible to isolate this chromosone or can they detect if we are carrying it?

    • Johanna says:

      You’re right – it’s complicated! I would look at the inheritance like this:

      Everyone carries two CDH1 genes: one from our mother, and one from our father. Even if only one of the genes has a mutation, a person has a high risk of gastric cancer (because the gene is “autosomal dominant”). This is different than inheriting blue eyes, for example – because to have blue eyes you must inherit the blue-eye gene from both parents (because the gene for blue eyes is “autosomal recessive”).

      Now, when a person with a CDH1 mutation has children, there is a 50% chance that he/she will pass on the healthy CDH1 gene (the one they inherited from a non-affected parent), and a 50% chance that he/she will pass on the mutated gene (the one they inherited from an affected patient).

      For example, if your grandfather carried a CDH1 gene mutation, your mother had a 50% chance of inheriting the mutated gene and a 50% chance of inheriting the other, healthy gene from him. If she inherited the mutated gene from her father but a healthy gene from her mother, she still would be at high risk of developing gastric cancer. In the same way, you would have a 50/50 chance of inheriting either a mutated gene or a healthy gene from your mother.

      So basically, the 50/50 rule applies to each generation.

      As far as testing for the genetic mutation, research has shown that between 25% and 50% of families who are considered to have the Hereditary Diffuse Gastric Cancer syndrome have a known CDH1 gene mutation. There may be genetic mutations other than CDH1 that cause HDGC, but they are not known yet. If possible, it is best to perform genetic testing on a family member who is known to have diffuse gastric cancer. If a mutation is detected in that family member, the other family members would then be tested for the same mutation – each of them having a 50/50 chance of carrying the mutation.

  3. LeMarko Sanders says:

    Is CDH1 caused by H-pylori?

    • karen says:

      No, it is not. H-pylori is related to the intestinal type of stomach cancer as opposed to the diffuse type of stomach cancer. The diffuse type can be hereditary and is sometimes caused by a mutation in the CDH1 gene.

  4. c7513 says:

    Thank you, Amy, for explaining the mutation so clearly for all of us. Cindy Chelcun

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