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The MLH1 gene: your DNA's spell-checker | CION Cancer Clinics
MLH1 is a gene that fixes copying errors in your DNA. An inherited fault in MLH1 causes Lynch syndrome, which raises the risk of bowel, womb and several other cancers. This page explains what the gene does, how a fault leads to cancer, and why MLH1 missing from a tumour does not always mean the family has inherited anything. 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 MLH1 gene actually do?
- Which conditions are linked to MLH1?
- How does an MLH1 fault lead to cancer?
- The words you will meet, in plain language
- Is MLH1 loss in the tumour the same as an inherited fault?
- What families often get wrong about MLH1
- What this page cannot tell you
- Common questions about the MLH1 gene
The short answer
What does the MLH1 gene actually do?
MLH1 works like a spell-checker for your DNA. Every time a cell divides, it copies its whole instruction manual, and small typing errors creep in. MLH1 is one of the proteins that finds those errors and gets them fixed. When it does not work, mistakes pile up, and some of them can start a cancer.
MLH1 works as part of a team
The repair system is called mismatch repair. MLH1 pairs with a partner protein called PMS2, and together they act on errors spotted by another pair, MSH2 and MSH6. Faults in any of these four genes cause Lynch syndrome. MLH1 sits at the centre of the team, which is why losing it matters so much.
Why this gene gets so much attention
An inherited MLH1 fault is one of the commonest known causes of inherited bowel cancer. It also raises the risk of womb cancer and several others. Finding it early lets carriers start regular checks that can catch problems before they become serious.
Carrying an MLH1 fault is a statement about risk. It is not a diagnosis.Linked conditions
Which conditions are linked to MLH1?
The same gene can show up in four quite different situations. Knowing which one you are in changes everything that follows.
Lynch syndrome
One faulty copy inherited from a parent. It raises the risk of bowel, womb, ovary, stomach and urinary tract cancers, among others. This is by far the most common reason MLH1 appears on a report.
Two faulty copies
A child who inherits a faulty copy from each parent has a rare condition called constitutional mismatch repair deficiency. Cancers can start in childhood. It is more likely when parents are related by blood.
Skin tumours alongside Lynch
Some families also develop unusual oil-gland skin growths. This combination has its own name, Muir-Torre syndrome, and a skin finding can be the first clue to Lynch syndrome in a family.
Switched off in the tumour only
In many bowel and womb cancers, MLH1 is silenced inside the tumour by a chemical tag, not by an inherited fault. This is not passed on.
Often looks like
- An older person with one cancer
- No pattern in the family
Not sure whether this applies to you?
Ask an oncologistFrom fault to cancer
How does an MLH1 fault lead to cancer?
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You carry two copies of MLH1
One came from each parent. A single working copy is enough to keep mismatch repair running normally in every cell.
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An inherited fault removes one copy from birth
Every cell starts with only one working copy. Nothing is wrong yet, and a carrier usually feels completely well for many years.
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The second copy is lost in one cell
During life, the remaining copy can be damaged in a single cell, often in the bowel or womb lining, where cells divide constantly.
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Copying errors build up quickly
Without repair, that cell collects mistakes every time it divides. Doctors can see the pattern on a tumour test, where it is called microsatellite instability.
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A polyp can turn into cancer faster
In Lynch syndrome a polyp can become a cancer more quickly than usual. That is why carriers have colonoscopy far more often than other people.
On your report
The words you will meet, in plain language
- Mismatch repair
- The system that fixes copying errors in DNA. MLH1, PMS2, MSH2 and MSH6 are its main parts.
- Germline
- Present in every cell from birth, and so can be inherited. A fault found only in the tumour is called somatic.
- Microsatellite instability
- A pattern of copying errors seen in a tumour when mismatch repair has failed. It is often shortened to MSI.
- Immunohistochemistry
- A stain on tumour tissue showing whether the repair proteins are present. Loss of MLH1 usually comes with loss of PMS2.
- Promoter methylation
- A chemical tag that switches MLH1 off inside a tumour. It is usually acquired, not inherited.
- Penetrance
- How often a fault actually leads to cancer across everyone who carries it. For MLH1 it is high, but never all carriers.
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Side by side
Is MLH1 loss in the tumour the same as an inherited fault?
Inherited MLH1 fault
MLH1 switched off in the tumour
Present in every cell from birth
Found only inside the cancer
Relatives can be tested for it
Relatives do not need testing for it
Often younger people and several relatives
Often older people, with no family pattern
Confirmed by a blood test
Confirmed by a methylation test on tissue
Commonly believed
What families often get wrong about MLH1
"MLH1 loss in my father's tumour means we all carry it."
Not necessarily. MLH1 is often switched off inside the tumour only. Further tests on the tissue, and sometimes a blood test, tell the two apart.
"It only matters for bowel cancer."
The bowel is the main concern, but women carry a raised womb and ovary risk too. The stomach, small bowel and urinary tract can also be affected.
"A carrier will certainly get cancer."
Risk is raised, not settled. Many carriers never develop cancer, and regular colonoscopy removes polyps before they can turn into one.
"MLH1 can be fixed with treatment or diet."
An inherited fault cannot be corrected or reversed. What changes the outlook is checking early and often, and acting quickly on anything found.
Being straight with you
What this page cannot tell you
It cannot tell you whether your family carries an MLH1 fault. That answer comes from a counsellor who has drawn out the family tree, checked whether an affected relative's tumour was tested, and arranged the right test for the right person first.
It cannot read your report
MLH1 reports can name a harmful change, an uncertain one, or a tumour finding that turns out not to be inherited at all. Each leads somewhere different. Bring the report to someone qualified to read it rather than searching for the variant online.
Who this does not apply to
Most people do not need MLH1 testing. One older relative with bowel cancer, and no pattern of young diagnoses or womb cancer, rarely points to Lynch syndrome. If your question is about the tumour itself, for treatment choices, our targeted therapy pages cover tumour testing.
What your specific variant means is a question for the counsellor who ordered the test.Questions we are asked
Common questions about the MLH1 gene
Is MLH1 the same as Lynch syndrome?
MLH1 is a gene. Lynch syndrome is the condition caused when someone inherits a harmful fault in MLH1 or one of three partner genes. Everyone has the MLH1 gene. Only people with a faulty copy have Lynch syndrome.
How is an MLH1 fault inherited?
From either parent, to sons and daughters equally. Each child of a carrier has a one in two chance of inheriting it. A child who does not inherit the fault cannot pass it on to their own children.
Why did my relative's tumour test mention MLH1?
Bowel and womb cancers are often checked for missing repair proteins. If MLH1 was missing, it could be inherited or switched off in the tumour only. More tests on the tissue usually sort this out before anyone needs a blood test.
Which cancers does MLH1 raise the risk of?
Mainly bowel cancer, and womb cancer in women. Ovary, stomach, small bowel, urinary tract and some other cancers are also more likely than usual. The risk for each organ differs, and a counsellor can explain what applies in your family.
Is the test a blood test?
Yes. Testing for an inherited fault uses blood or saliva. Tests on tumour tissue answer a different question about the cancer itself. Both can be part of the same work-up, and your doctor will explain which one is being done.
Does MLH1 matter for treatment?
It can. Tumours that have lost mismatch repair, whether inherited or not, often respond well to immunotherapy. That decision is made on the tumour result by your oncologist, and it is separate from what the family needs to know.
Can children be born with two faulty copies?
Rarely, when both parents carry a fault in a mismatch repair gene. This is more likely when parents are related by blood. Tell your counsellor if that applies, so both partners can be offered testing before or during pregnancy.
Where do I start if I am worried?
Write down who had bowel, womb or related cancers, and roughly at what age, on both sides. Find out whether any tumour was tested for repair proteins. Take that list to a genetic counsellor or call the CION helpline for advice.
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
- MedlinePlus Genetics — MLH1 gene
- GeneReviews (NCBI) — Lynch Syndrome
- MedlinePlus Genetics — Lynch syndrome
- National Cancer Institute — Genetics of Colorectal Cancer (PDQ)
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
MLH1 mutation: which cancers and what riskEvery organ an MLH1 fault can affectMLH1 promoter methylationWhen MLH1 is switched off in the tumour onlyMLH1 carriers have the highest Lynch risksHow MLH1 compares with the other Lynch genesTesting the family for MLH1Who should be tested once a fault is found
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Did a relative's tumour report mention MLH1?
Tell us what the report says and who else in the family had cancer. We will help you work out whether a genetic referral makes sense. One helpline serves every CION centre.