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Beyond CDH1: CTNNA1 and the other stomach cancer genes | CION Cancer Clinics
CDH1 is not the only gene behind inherited stomach cancer. A few families carry a fault in its partner gene, CTNNA1, and others have a syndrome such as Lynch in which stomach cancer is one risk among several. Many find no gene at all. This page explains the other genes, how a team searches for the cause, and what happens when the answer is none. 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 if our family has stomach cancer but no CDH1 fault?
- Which other genes can cause stomach cancer in a family?
- How does a genetic team look for the cause?
- The words you will meet, in plain language
- How is CTNNA1 different from CDH1?
- What this page cannot tell you
- Four things families assume after a negative CDH1 test
- Common questions about CTNNA1 and other stomach cancer genes
The short answer
What if our family has stomach cancer but no CDH1 fault?
CDH1 is the best-known gene behind inherited stomach cancer, but it is not the only one. A small number of families carry a fault in a partner gene called CTNNA1. Others turn out to have a different syndrome in which stomach cancer is one of several risks. Many families never find a gene at all.
Why CTNNA1 comes up
CDH1 makes a protein called E-cadherin that holds cells together. CTNNA1 makes a second protein, alpha-E-catenin, which anchors E-cadherin inside the cell. If either link breaks, cells in the stomach lining can come loose and grow where they should not. That is why the two genes can cause a similar pattern.
What a negative CDH1 result does and does not mean
If the relative who had cancer tested negative for CDH1, the family is less likely to have the classic syndrome. It does not mean the family history no longer counts. Relatives are still watched on the strength of the history itself.
Why this matters in India
Stomach cancer is common in parts of the country, and most of it is not inherited. Telling the inherited cases apart is how families avoid both missed risk and needless surgery. Families who married within the community over several generations may share a fault more often, which is one more reason to record both sides of the family carefully.
Finding no gene is a common result. It is not a failed test.The other suspects
Which other genes can cause stomach cancer in a family?
Each of these behaves differently, and each leads to a different plan.
CTNNA1
Found in a small number of families with the diffuse stomach cancer pattern and no CDH1 fault. Very few families have been studied, so the size of the risk is not yet known.
Usually offered
- Specialist surveillance endoscopy
- Surgery discussed only with a strong history
Lynch syndrome genes
Best known for bowel and womb cancer. Stomach cancer is also raised in some Lynch families, usually the more common intestinal type rather than the diffuse type. Whether stomach checks are offered depends on the exact gene and on who in the family was affected.
Polyposis syndromes
Some rare conditions cause many polyps in the stomach or bowel. A few carry a stomach cancer risk. They are usually suspected from what the endoscopy shows, rather than from the family tree alone. A report that mentions many polyps is worth taking to a counsellor.
No gene found
Most families who meet the criteria for inherited stomach cancer test negative for every known gene. Their relatives are still offered surveillance based on the family pattern.
Not sure whether this applies to you?
Ask an oncologistHow the search works
How does a genetic team look for the cause?
Draw the family tree
The counsellor records every stomach, breast and bowel cancer on both sides, with the type and the rough age at diagnosis.
Check the tumour type
Whether a relative's cancer was diffuse or intestinal changes which genes are most likely. Old pathology reports help a great deal.
Test the relative who had cancer
A multi-gene panel covering CDH1, CTNNA1 and the other stomach cancer genes is usually run on them first, if they are alive and willing.
Test well relatives for the exact fault
If a fault is found, others are tested for that single change. This is quicker and cheaper than a full panel.
If nothing is found, plan from the history
Relatives are offered surveillance based on the pattern. The case can be reopened as new genes are discovered.
On your report
The words you will meet, in plain language
- CTNNA1
- The gene that makes alpha-E-catenin, a partner protein to the one made by CDH1.
- HDGC
- Hereditary diffuse gastric cancer. The family condition these genes can cause.
- Diffuse type
- A stomach cancer that spreads in scattered cells under the lining, rather than as a lump.
- Intestinal type
- The more common stomach cancer, which forms a visible growth and is often linked to infection.
- Multi-gene panel
- A single test that checks many cancer genes at once from one blood sample.
- Germline
- Present in every cell from birth, and so it can be passed on. The opposite, somatic, means found only in the tumour.
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Side by side
How is CTNNA1 different from CDH1?
CTNNA1
CDH1
Very few families studied
Many families studied over decades
Stomach cancer risk not yet measured
Stomach cancer risk clearly high
Breast risk unknown
Lobular breast cancer risk raised in women
Endoscopy usually preferred to surgery
Preventive stomach removal usually discussed
Being straight with you
What this page cannot tell you
It cannot tell you which gene, if any, runs in your family. That depends on the tumour types, the ages and the test results of relatives, and it takes a trained counsellor to read them together. What your specific variant means is a question for the counsellor who ordered the test.
It cannot put a number on CTNNA1 risk
The honest answer is that nobody can yet. The evidence comes from a small number of families, mostly outside India. Guidance is likely to change as more carriers are found.
Who this does not apply to
Most people with one relative who had stomach cancer later in life do not need genetic testing. The usual causes are Helicobacter pylori infection, smoking, salted and smoked food, and age. Testing is considered when stomach cancer came young, came in several relatives or came alongside lobular breast cancer. A change found only inside a tumour is covered on our targeted therapy pages.
Unsure whether your family fits? Call the helpline and describe the pattern. You will get an honest answer.Commonly believed
Four things families assume after a negative CDH1 test
"The CDH1 test was negative, so our family is in the clear."
Only CDH1 has been ruled out. Another gene may be involved, or none that can yet be found. The family history still guides who needs watching.
"CTNNA1 is just the same as CDH1."
The two genes work together, but CTNNA1 has been studied far less. Carriers are usually offered surveillance first rather than being moved straight to surgery.
"If no gene is found, surveillance is pointless."
Families with a strong pattern and no gene can still benefit from specialist endoscopy. The plan is built on the history instead of on a result.
"We should test everyone in the family for every gene."
Testing a well relative first often gives an answer nobody can use. The relative who had cancer is the best person to test first, where that is possible.
Questions we are asked
Common questions about CTNNA1 and other stomach cancer genes
Is CTNNA1 included in a standard stomach cancer panel?
It is included in many wider hereditary cancer panels, but not in every one. The gene list is printed on the report. If CTNNA1 is missing and your family history is strong, ask your counsellor whether it should be added.
Should a CTNNA1 carrier have their stomach removed?
Not routinely. Because the risk is not yet known, most guidance suggests specialist endoscopy instead. Surgery may be discussed in families where several relatives developed diffuse stomach cancer. It is one option among several.
Do women with CTNNA1 need breast checks?
There is not enough evidence to say CTNNA1 raises breast cancer risk. Breast checks are usually planned from the family history. If lobular breast cancer runs in the family, your counsellor may suggest closer watching.
Our relative who had cancer has died. Can we still test?
Sometimes. A stored tissue block from an old surgery or biopsy can occasionally be tested. If that is not possible, a well relative can be tested, though a negative result then tells you less.
Can Lynch syndrome cause stomach cancer?
Yes, in some families, usually the intestinal type. Lynch carriers may be offered stomach checks depending on the gene and family history. It is covered on our Lynch syndrome pages.
My result says variant of uncertain significance in CTNNA1. What now?
It means a change was found whose effect is not yet known. It should not change your care or lead to surgery. Ask how you will be told if the laboratory reclassifies it later.
Can we have the whole family tested at once?
It is better to test in order. Start with the person who had cancer, then test others for any fault found. This saves cost and gives clearer answers for every relative.
Where do we start?
Write down every stomach, breast and bowel cancer in the family, with the type and the rough age. Take it to a genetic counsellor or your oncologist. Call the CION helpline if you are not sure who to approach.
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)
Medical Oncologist
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Sources
- GeneReviews (NCBI) — Hereditary Diffuse Gastric Cancer
- MedlinePlus Genetics — Hereditary diffuse gastric cancer
- GeneReviews (NCBI) — Lynch Syndrome
- 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.
Keep reading
Related pages
The CDH1 gene: what it doesThe main stomach cancer gene, explained firstHereditary diffuse gastric cancer explainedThe family condition these genes causeGastric and small bowel surveillance in LynchIf Lynch turns out to be the causeSurveillance for CDH1 carriersWhat specialist stomach checks involve
Talk to us
Stomach cancer in the family, but a negative CDH1 test?
Tell us who was diagnosed, with which type and at what age. We will help you reach a counsellor who can decide what, if anything, to test next. One helpline serves every CION centre.