To the Family of a CDH1 Mutant
Updated: May 2
As the first person in my family to be diagnosed with a mutation on the CDH1 gene, it is my burden to share relevant information with everyone who could potentially be impacted. This post is part of my ongoing attempt to do just that.
First, what does this genetic mutation mean?
This mutation is rare, was only discovered in the 1990s, is still grossly misunderstood, and it is believed that fewer than 500-1000 families worldwide have this mutation.
A CDH1 mutation can lead to:
Hereditary Diffuse gastric cancer
References and Resources
Genetics Home Reference: https://ghr.nlm.nih.gov/condition/hereditary-diffuse-gastric-cancer
No Stomach for Cancer: http://www.nostomachforcancer.org/about/hereditary-diffuse-gastric-cancer
Facing Our Risk of Cancer Empowered:
BELOW ARE MY GENETIC TESTING RESULTS
Second, who could be impacted?
I received genetic testing after being diagnosed with invasive lobular breast cancer in 2018. Because of my young age, and my personal family history of cancer, it was determined genetic testing could potentially help me make breast cancer treatment decisions. It was a complete shock when I was diagnosed with a pathogenic variant in CDH1, as I had no known family history of gastric cancer at the time.
Let's look at the facts first:
I tested positive for a pathogenic variant in the CDH1 gene shortly after my breast cancer diagnosis (see above results);
My mom was tested next due to her personal breast cancer history, she subsequently tested negative;
My dad was tested next. He tested positive. His test resulted in the same pathogenic variant in the CDH1 gene as me;
My brother was then tested. He tested positive. His test resulted in the same pathogenic variant in the CDH1 gene as my dad and I;
This genetic mutation is autosomal dominant, meaning an affected individual (CDH1+) only needs to inherit one copy of the mutant gene. Thus, parents who are CDH1+ have a 50-50 chance of passing the mutation on to their children (see a picture example of autosomal dominant inheritance below). This is different than a recessive gene which requires both parents to pass on the mutation.
Genetic counselors are trained to start testing with the individual diagnosed with cancer (me), and work there way outward with testing of closest relatives first. This way they can trace the gene mutation without performing any unnecessary tests on family members who are not likely to have the mutation. Hence, my parents were tested first, then my brother, and then it is recommended that my dad's siblings be tested, and so on. The testing follows positive results. If individuals test negative for the gene, it stops there. They and their children are not at risk for inheriting the CDH1 mutation and subsequent HDGC syndrome because the mutation cannot skip generations. If an individual tests positive, then their children have a 50-50 risk, and so on.
Informing relatives is not fun. Who wants to talk about cancer, let alone the chance that they could have inherited this awful disease as well! It is also an individual decision whether to be tested, and if so, what to do about the results.
We are also not 100 percent sure which side of the family this mutation came from. This makes informing relatives that much more difficult. Testing of my dad's parents is not possible to determine which side of the family had the mutation to begin with. Although we suspect it was from my grandfather's side due to a history of breast cancers at young ages, and one incidence of gastric cancer in my father's cousin, on my grandfather's side. Unfortunately, until someone tests positive on either side of the family, we just will not know for sure.
It is mine and my dad's responsibility to point people to resources that could be helpful, and assist people in getting tested if that is what they desire. I realize that this is a difficult topic, and personal decision for everyone, but I urge you to consider being tested if you are at risk of inheriting a CDH1mutation. If you are negative, it will be a relief, and you will have peace of mind that your children and grandchildren are safe from a CDH1 mutation. If you are positive, there are a lot of risk reducing strategies that can be taken, and regular cancer screenings can be initiated at the very least. No, you don't have to do anything drastic like me, but it could help save your life, or the lives of your children and/or grandchildren. All I want, is for my family to be aware, and not have to go through what I have been through these past couple of years. After going through cancer personally, I wouldn't wish it on my worst enemy, let alone my family!
Third, what to do if you want to be tested?
There are many ways to be tested, but generally speaking, you will want to speak with your primary care provider and seek a referral to a genetic counselor. Let them know that someone in your family has tested positive for the CDH1 gene mutation, and that should do the trick. Before meeting with the genetic counselor, they will likely request that you complete a family history of cancers and known mutations. My genetic testing results (above) can be used to fulfill this, but always feel free to reach out and I can provide the full report and the family history questionaire I completed (to make things easier).
Direct to consumer (DTC) testing (23 and me, or similar test kits provided by private companies) are not recommended. These companies are not held to the same standards as healthcare driven genetic testing, and do not have the same privacy laws which protect your health information. I was told by a genetic counselor that these tests are not as reliable, and if you were to test positive for a mutation through a DTC, you would still need to have genetic testing done through a healthcare facility to confirm, which would mean you would have to pay for testing twice. Also, it is known that DTC can provide false negative results, because not all variants of all genetic disorders are included in the testing. This means you could test negative for a CDH1 variant falsely, yet really be positive for another CDH1 variant that wasn't included in the test. This could provide a false sense of security, when in reality you actually have a positive test result.
A couple of things to keep in mind before being tested:
If you test positive for a genetic mutation, you cannot be discriminated against in terms of healthcare insurance coverage and employment. There is a federal law that protects against this (Genetic Information Nondiscrimination Act - GINA: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568442/)
You may want to secure life insurance and/or critical illness insurance before being tested. If you test positive, you will likely not be able to receive these types of insurances again. I am out of luck since I was diagnosed with breast cancer before I was able to secure these things, but you don't have to be!
If you are my relative, and you wish to join the National Institutes of Health study on CDH1 which my father and I are enrolled in, let me know and I can get you all the information. This study has provided me with all of my stomach related care (EGDs, stomach biopsies, total gastrectomy). You would need to be officially enrolled in the study, and then they would send a genetic testing kit to your house free of charge, you would have access to the leading clinical experts specializing in the CDH1 gene, and would be allowed free access to regular screenings, surgery, etc. Here is the link to the clinical study: https://clinicaltrials.gov/ct2/show/NCT03030404?term=17-C-0043&rank=1
References and Resources
Genetic Testing Facts and Links: https://medlineplus.gov/genetictesting.html
Genetic Testing FAQ- NIH National Human Genome Research Institute: https://www.genome.gov/FAQ/Genetic-Testing
Regulation of Genetic Testing- NIH National Human Genome Research Institute: https://www.genome.gov/about-genomics/policy-issues/Regulation-of-Genetic-Tests
What is Genetic Testing- NIH: https://ghr.nlm.nih.gov/primer/testing/genetictesting
Fourth, treatment planning options
If you are related to me, then you may qualify for genetic testing because I was diagnosed with Lobular Breast Cancer (LBC) at 32 years old, and signet ring cells were found in my stomach via biopsy, and following my total gastrectomy.
Fifth, my plea to relatives of CDH1 mutants
I get your hesitation. I get that you might feel overwhelmed by all this information. I get that you might think 50-50 is not bad odds, and that you likely won't have this mutation. I too thought these things before my cancer diagnosis and before being diagnosed with this rare mutation. I get it if you don't want to think about this right now. I get that we all live busy lives and it is easier to ignore this and put it off until later.
I have felt all of these feelings, and I too put things off, which meant it was almost too late for me. I don't want any of you to go through what I have been through. I wouldn't wish cancer on anyone, and I truly hope this mutation is not manifested outside of my immediate family. This mutation sucks. The physical and psychological aspects are no fun. But, like I said previously, it is my burden to let you know. With this information, I hope you will think about your options, talk with your doctor, talk with your family, and make the best decision for you. I have no expectations outside the fact that I want you to take this seriously and take the time to think it through. Also, if you have children, take that into your considerations. Just because you haven't had a cancer diagnosis, doesn't mean you haven't passed the mutation on. It also doesn't mean one of them couldn't turn out like me, with a cancer diagnosis in the prime of their life.
Please reach out to me if you have questions, or anything doesn't make sense. There is a lot of information here. I am happy to be a sounding board and resource. Feel free to call, text, email: firstname.lastname@example.org, or send me a private message here: Contact
Take Great Care, Kate