What Is a CDH1 Gene Mutation? Which Cancer Risks Does It Increase?

What Is an Inherited CDH1 Mutation? What You Need to Know – Summary

• The name CDH1 comes from "Cadherin 1". The CDH1 gene is located on chromosome 16 and helps cells adhere to each other to form tissues and organs.
• A very rare and serious condition called blepharocheilodontic syndrome (BCD) is occasionally associated with CDH1.
• In the CDH1 gene, an inherited mutation is associated with an increased risk of certain cancers in people who carry it. There are screening and prevention guidelines for certain cancers for people with this mutation.
• Clinical trials are also available for people who test positive for a CDH1 mutation. People diagnosed with a CDH1 mutation who have also been diagnosed with cancer may participate in clinical trials or receive certain treatments.
• Both men and women can carry a mutation in the CDH1 gene.

Which Cancers Have an Increased Risk With an Inherited CDH1 Mutation?

If you test positive for an inherited CDH1 mutation, a review of your personal and family cancer history, along with help choosing the best plan to manage your cancer risk, from a genetics specialist is recommended.

Risks for Women

Among people with a CDH1 mutation, "lobular breast cancer" is a form of breast cancer that they have a higher risk of developing. The estimated lifetime risk of breast cancer for a woman carrying this mutation is 39 – 52%.

Risks for Both Women and Men

Stomach Cancer

Among women and men who carry an inherited CDH1 mutation, "diffuse gastric cancer" is a form of stomach cancer that they have a higher risk of developing.

• The lifetime risk of developing stomach cancer is 67% in men and 83% in women. This compares with less than 1% in the general population.
• Compared with 68 in the general population, the average age at diagnosis in CDH1 carriers is 37. 

Some researchers have shown that a CDH1 mutation may also increase the risk of other types of cancer. However, these studies are inconclusive, and the lifetime risks for those cancers have not been clearly defined. For this reason, genetics specialists often help people with a CDH1 mutation understand their additional cancer risks by reviewing their family history of cancer.

The graphs below show the lifetime risk of stomach and breast cancer for people with an inherited CDH1 mutation. 

Risk Management for People With a CDH1 Mutation – How Should They Be Screened, and What Precautions Should Be Taken?

The United States National Comprehensive Cancer Network (NCCN) provides risk management guidelines for men and women with a CDH1 mutation. A review of your personal and family cancer history and help determining the best risk management plan from a genetics specialist is advised.

Screening and Prevention for Stomach Cancer

Experts recommend that people with an inherited CDH1 mutation undergo risk-reducing surgery between the ages of 18 and 40 in which the entire stomach is removed (prophylactic total gastrectomy). Stomach removal is not recommended for people younger than 18, but it may be considered for patients for whom this is clear, especially those with a family member diagnosed with stomach cancer before the age of 25.

CDH1 mutation carriers whose stomachs have not been removed are advised, every 6-12 months, to have multiple random biopsies with upper endoscopy. Upper endoscopy involves passing a video camera down the esophagus into the stomach. This gives doctors an opportunity to examine the stomach more closely. During this procedure, the surgeon may take a tissue sample from the stomach to look for cancer.

Screening and Prevention for Breast Cancer

For women who carry an inherited CDH1 mutation, experts recommend annual mammogram screening (3D mammograms if available), along with annual scans starting at age 30, or earlier if there is a family history of breast cancer, using breast MRI (MRG) as recommended.

There is not enough research for experts to recommend risk-reducing mastectomy (removal of both breasts for prevention) to women. Women considering risk-reducing mastectomy should make a decision together with their healthcare professionals based on their family history of breast cancer.

Screening and Prevention for Other Types of Cancer

There is not enough research showing a benefit from screening and prevention for other cancers in people with a CDH1 mutation. For this reason, experts recommend managing these risks based on a family history of cancer. People with a CDH1 mutation may also participate in cancer screening and prevention studies.

Medical Decisions for People With an Inherited CDH1 Mutation Who Have Been Diagnosed With Cancer

There is currently neither a specific cancer treatment approved for people with a CDH1 mutation nor a guideline for treating cancer in these people.

Surgical Decisions for Women Diagnosed With Breast Cancer

Because of the risk of a second breast cancer, women who test positive for an inherited mutation in CHD1 and are diagnosed with breast cancer may choose an alternative to lumpectomy and radiation in the form of bilateral mastectomy. Mutation carriers who undergo mastectomy have a much lower chance of developing a second breast cancer.

Other Medical Concerns for People Who Carry an Inherited CDH1 Mutation

Cleft lip and cleft palate (abnormalities of the lip or palate that develop in the womb) may also be associated with an inherited CDH1 mutation. A very rare syndrome called blepharocheilodontic syndrome (BCD) has been seen in some people with an inherited mutation in the CDH1 gene. This disorder is present from birth and causes abnormalities that mainly affect the eyelids and mouth (openings on both sides of the upper lip (bilateral cleft lip) and an opening in the palate (cleft palate)). Despite the association between CDH1 gene mutations and an increased cancer risk, it is unclear whether everyone affected by this syndrome has an increased risk of developing cancer.

Parents also have the option of using assisted reproductive technology and preimplantation genetic diagnosis to select embryos without inherited CDH1 mutations.