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The CDH1 gene: the cell glue behind hereditary stomach cancer | CION Cancer Clinics
CDH1 makes E-cadherin, a protein that holds cells together. An inherited fault in it raises the risk of a hard-to-see stomach cancer and, in women, lobular breast cancer. This page explains what the gene does, how a fault leads to cancer, which families should think about it, and why most people with stomach cancer in the family do not carry it. At CION Cancer Clinics, our oncologists explain what a gene result means for you and your family, and plan the checks that follow.
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Medically reviewed by Dr. Naresh GunduConsultant Medical Oncologist · MBBS, DNB (Internal Medicine), DM (Medical Oncology, AIIMS) · last reviewed September 2026, next review due September 2027
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On this page
- What does the CDH1 gene actually do?
- Which parts of the body does a CDH1 fault affect?
- How does a faulty CDH1 gene lead to cancer?
- The words you will meet, in plain language
- How is a CDH1 stomach cancer different from the usual kind?
- Four things families assume about CDH1
- What this page cannot tell you
- Common questions about the CDH1 gene
The short answer
What does the CDH1 gene actually do?
CDH1 carries the instruction for a protein called E-cadherin. It works like glue between neighbouring cells, holding them in neat, orderly sheets. When the gene is faulty, cells in the stomach lining and the breast can come loose and grow in a scattered way that is hard to see.
Why this particular glue matters
Most tumours grow as a lump that a scan or a camera can find. Cells without working E-cadherin behave differently. They slip between healthy cells one by one and spread through the wall of the stomach like ink in cloth. That pattern is called diffuse, and it is the reason CDH1 gets special attention.
The syndrome it causes
An inherited fault in CDH1 causes a condition called hereditary diffuse gastric cancer. The name describes the main risk, a stomach cancer that spreads in sheets rather than forming a lump. Women who carry the fault also have a raised risk of lobular breast cancer, a type that grows in a similar scattered way.
Carrying a CDH1 fault is a statement about risk. It is not a cancer diagnosis.Where it shows up
Which parts of the body does a CDH1 fault affect?
The gene is active in many tissues, but the raised risk is concentrated in two places. A few families also notice a third pattern.
The stomach
The main concern. Diffuse stomach cancer can begin as tiny clusters of cells under a normal-looking lining. Early on it rarely causes pain or indigestion that feels different from everyday acidity.
Why it is hard to find
- No lump forms in the early stage
- The lining often looks normal on camera
- Early spots are very small and scattered
The breast
Women who carry the fault have a raised risk of lobular breast cancer. This type can be harder to feel and harder to see on a mammogram, which is why breast MRI is often part of the plan.
Cleft lip and palate
Some CDH1 families also have relatives born with a cleft lip or cleft palate. It is uncommon, but it is worth mentioning to the counsellor when you draw the family tree, because it can point to the gene.
What it does not usually affect
The bowel, ovaries, prostate and blood are not the main concern with this gene. If your family has a pattern of those cancers, a different gene is a more likely explanation and your counsellor will look there.
Not sure whether this applies to you?
Ask an oncologistFrom fault to cancer
How does a faulty CDH1 gene lead to cancer?
Two copies from birth
Everyone has two copies of CDH1, one from each parent. A carrier is born with one working copy and one faulty copy in every cell of the body.
One copy is enough, for now
A single working copy still makes enough E-cadherin to keep cells stuck together. This is why carriers are healthy for years and often for life.
The second copy is damaged in one cell
During ordinary life, the working copy can be damaged in a single stomach or breast cell. That cell now makes no glue at all.
The cell drifts loose
Without its anchor, the cell can grow and move between its neighbours. Most such cells stay quiet for a long time. Some go on to form a cancer that spreads through the tissue.
Chance decides the rest
Whether that second step happens, and when, is partly luck. Two brothers carrying the same fault can have very different health.
On your report
The words you will meet, in plain language
- CDH1
- The short name of the gene. It is read out letter by letter, and it makes the E-cadherin protein.
- E-cadherin
- The protein that holds cells together. On a biopsy report, loss of E-cadherin staining is a clue that points to this gene.
- Diffuse gastric cancer
- A stomach cancer that spreads through the wall in sheets rather than growing as a lump. It is also called signet ring cell cancer, after the shape of the cells.
- Lobular breast cancer
- A breast cancer that starts in the milk-producing lobules and often grows in thin lines rather than a firm lump.
- Pathogenic variant
- A spelling change in the gene that is known to break it. This is what people mean by a CDH1 fault or mutation.
- Germline
- Present in every cell from birth and so able to be passed on. A fault found only inside a tumour is called somatic.
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Side by side
How is a CDH1 stomach cancer different from the usual kind?
Diffuse type, linked to CDH1
Common intestinal type
Spreads in sheets through the stomach wall
Usually grows as a visible lump or ulcer
Can appear at a young adult age
More common in older adults
Often missed by a routine camera test
Usually seen clearly on endoscopy
May run in the family through one gene
Often linked to infection, diet or tobacco
Commonly believed
Four things families assume about CDH1
"Stomach cancer in our family is from spicy food and acidity."
Diet and infection explain most stomach cancer. But diffuse stomach cancer at a young age, in more than one relative, can point to an inherited gene instead. The pattern matters more than the food.
"A normal endoscopy means the stomach is safe."
For a CDH1 carrier, a clear camera test is reassuring but not final. Early diffuse cancer can sit under a normal-looking lining, which is why carriers are offered more than a routine check.
"Only women need to worry about this gene."
Men and women carry and pass on CDH1 equally. The stomach risk applies to both. Only the breast risk is mainly a concern for women.
"If I carry it, I will definitely get cancer."
The risk is substantially raised, but it is not certain. Many carriers stay well, and the ones who are watched or treated early have real choices.
Being straight with you
What this page cannot tell you
It cannot tell you whether your family carries a CDH1 fault. That answer comes from a genetic counsellor who has drawn your family tree, looked at the pathology reports of relatives who had stomach or breast cancer, and arranged the right test for the right person.
It cannot read your report
The exact variant matters. Some CDH1 changes clearly break the gene. Others are uncertain and should not change any decision. What your specific variant means is a question for the counsellor who ordered the test.
Who this does not apply to
Most people with a relative who had stomach cancer do not need a CDH1 test. A single case in an older relative, especially a lump-forming type, is usually not inherited. Testing is worth discussing when diffuse stomach cancer appears young, when it appears in more than one relative, or when stomach and lobular breast cancer both run in the family.
If you are unsure whether your family pattern counts, describe it to the helpline and ask whether a referral makes sense.Questions we are asked
Common questions about the CDH1 gene
Is CDH1 the same as a BRCA gene?
No. Both can raise breast cancer risk, but they are different genes doing different jobs. BRCA genes repair damaged DNA. CDH1 holds cells together. The cancers they cause, and the checks that follow, are different, so your plan will be different too.
How common is a CDH1 fault?
It is rare. Most stomach cancer in India is not caused by an inherited gene. CDH1 is looked for when a family has an unusual pattern, such as diffuse stomach cancer in a young adult or several relatives with the diffuse type.
Can a CDH1 fault be passed to my children?
Yes. Each child of a carrier has an even chance, one in two, of inheriting it. Sons and daughters are equally likely to inherit. A child who does not inherit the fault cannot pass it on to their own children.
Does H. pylori infection matter if I carry CDH1?
Doctors usually test for this stomach infection and treat it if found, because it adds its own risk to the stomach lining. Clearing it does not remove the inherited risk, but it removes one extra source of damage.
What test finds a CDH1 fault?
A germline genetic test, usually on a blood or saliva sample. CDH1 is often included in a panel that checks several genes linked to stomach and breast cancer at once. A tumour test answers a different question and belongs with targeted therapy.
Can lifestyle changes switch the gene back on?
No. The fault is in every cell and cannot be corrected or reversed. Not smoking, limiting alcohol and treating stomach infections still help overall health, but the real protection for carriers comes from close checks or preventive surgery.
Are the symptoms of CDH1 stomach cancer different?
Early on there are often no symptoms at all. Later signs such as feeling full quickly, weight loss or vomiting are the same as other stomach problems. This is why carriers cannot wait for symptoms and are offered planned checks instead.
Who should I speak to first?
A genetic counsellor or your oncologist. Bring a list of relatives with stomach or breast cancer, their age at diagnosis and any pathology reports you can find. Call the CION helpline if you are not sure where to start, and someone will guide you.
Your Specialists
Meet CION's oncologists. Bring your family history or genetic report to them.
Our medical oncologists see people with a strong family history of cancer, arrange genetic counselling and testing where it fits, and plan the checks that follow.
Medical Oncologist
Dr. C. Raghavendra Reddy
MBBS(Gold Medal), DNB(General Medicine), DM(Medical Oncology)(Gold Medal)
Medical Oncologist
Dr. Bharati Devi Gorantla
MBBS, MD(General Medicine), DM(Medical Oncology)(Adyar,Chennai), ECMO, MRCP SCE(UK)
Medical Oncologist
Dr. Owais Mohammed
MBBS, MD (General Medicine), DrNB (Medical Oncology), ECMO, MRCP SCE (Medical Oncology) (UK)
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Sources
- GeneReviews (NCBI) — Hereditary Diffuse Gastric Cancer
- MedlinePlus Genetics — CDH1 gene
- MedlinePlus Genetics — Hereditary diffuse gastric cancer
- National Cancer Institute — Genetic Testing for Inherited Cancer Susceptibility Syndromes
This page is general information, not a prescription. Do not change or stop any treatment based on what you read here. If anything is worrying you, contact your own treating team — or call our helpline and we will help you reach the right specialist.
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