6 Questions Answered about the CDH1 Gene Mutation & Stomach Cancer

Smiling female doctor talking to patient.

Surgeon Vivian Strong says people who learn they have a CDH1 mutation should talk to their doctor about the possibility of preventive stomach removal to reduce risk of cancer.

Stomach (gastric) cancer is the third leading cause of cancer deaths in the world today. About 10% of these cancers are due to a genetic mutation inherited from a parent. One specific mutation, called CDH1, puts a person at very high risk for a rare but lethal form of stomach cancer. Memorial Sloan Kettering surgeon Vivian Strong discusses this risk and answers key questions for patients.

1. Is stomach cancer genetic? What does it mean to have a CDH1 mutation?

Having a CDH1 mutation means that you are at high risk for developing a very aggressive form of stomach cancer called hereditary diffuse gastric cancer (HDGC). The CDH1 mutation also puts women at risk for a certain form of breast cancer called lobular breast cancer. There are different forms of CDH1 mutations, so the precise risk from the mutation alone can be hard to determine. But for those who have the mutation in addition to a family history of stomach cancer and/or a family history of lobular breast cancer, there is a 70% lifetime risk of developing HDGC in men and a 56% risk for women. Women with the CDH1 mutation also have a 42% lifetime risk of developing lobular breast cancer.

2. Should I be tested for the CDH1 mutation?

Your doctor can help you decide if you need testing for this mutation. If you have family members who have had stomach cancer or lobular breast cancer, it is a good idea to discuss whether a genetic test is right for you. In addition, a genetic counselor can provide clear and relevant information about genetic risk factors to support you in making a decision about testing.

3. What should I do if I have a CDH1 mutation?

If you are found to have a CDH1 mutation, it is important that you discuss the result with a clinical genetics expert who will help to determine your overall risk. Not everyone who inherits a gene mutation for HDGC will develop cancer. But if your risk is high, you may want to consider a procedure called risk-reducing gastrectomy — stomach removal — as a way of avoiding stomach cancer.

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HDGC is nearly impossible to detect at an early stage. It starts with a tiny spot of cancer cells that are very hard to see, which immediately burrow deep into the wall of the stomach. Even if a gastroenterologist were studying the stomach surface through an endoscope, it would look normal. Because HDGC is very difficult to cure once it becomes invasive, we recommend stomach removal in people thought to be at high risk.

4. How is stomach removal surgery performed?

In this procedure, we remove the entire stomach and connect the esophagus to the small intestine. At MSK, we are increasingly using a minimally invasive approach called robotic gastrectomy. It involves small incisions, which allows patients to recover faster and get back to their life sooner. After surgery, most patients stay in the hospital for five or six days to recover and start getting used to eating again.  

I have currently done over 350 robotic stomach surgeries, among the most in the US. With the robotic incisions, there is less scar tissue that forms in the abdomen, which means that if a patient ever needs to have another operation in the future, like an appendix or gallbladder removal, there will be a better chance for a minimally invasive operation with better results. It has been so rewarding to see the difference that this less invasive approach makes for the recovery of my patients.

5. Can I live without a stomach? What is it like?

There’s a widespread misconception that you need a stomach to live, when you really don’t. You can have a normal life with some manageable changes and adjustments. The main change is in eating six smaller meals spaced out through the day with frequent snacking for the first few months after surgery. There is some real work and adjustments that need to be made in the beginning, and we are there for our patients as often as they need us.

After a couple months, the new connections begin to stretch and people can eat larger portions. In fact, many of my patients will tell me that by six to eight months after surgery, they are eating about 80% of what they ate prior to surgery, with continued improvements over the first year or two. Some patients even tell me they are eating so well they jokingly ask if I forgot to remove their stomach!

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6. If I have a CDH1 mutation but no family history of stomach cancer, should I still consider stomach removal surgery?

This is a question we are studying closely. Since an increasing number of Americans are undergoing genetic testing, we’re identifying more people with CDH1 mutations but no family history of stomach cancer. Along with geneticist Zsofia Stadler, I just published the largest reported single-institution experience of patients with stomach cancers harboring CDH1 mutations in JAMA Surgery. In a study of more than 180 MSK patients, we found that for people with the mutation who do not have a family history, there is still a quantifiable risk of developing stomach cancer, although it appears that the risk is lower than for those who have a family history.

Overall, the most important factors to consider when making a decision include:

  • the specific type of genetic mutation
  • your family history
  • your overall health and fitness to have an operation
  • the results from an endoscopy with sampling biopsies

Each patient needs to be evaluated individually and should meet with a gastric specialty surgeon, such as me, and a genetics doctor who specializes in this area, such as Dr. Stadler, as well as a gastrointestinal doctor who will examine your stomach with an endoscope to determine the best way to keep you safe.

It is important to seek guidance from a specialty center such as MSK, where experts in this type of genetic mutation can meet with you to discuss particular details of your family and personal history to help you decide on next steps.