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The genes behind HBOC besides BRCA1 and BRCA2 | CION Cancer Clinics
BRCA1 and BRCA2 cause most HBOC, but not all of it. PALB2 carries a breast cancer risk close to BRCA, several other genes raise risk more moderately, and a few mainly affect the ovaries. This page explains which genes matter, what each one usually changes, and why a negative BRCA result from years ago may not be the full answer for your family. At CION Cancer Clinics, our oncologists plan screening and care for families with an inherited cancer syndrome, explained in plain words.
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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
- Which genes besides BRCA1 and BRCA2 can cause HBOC?
- What does each of these genes do to risk?
- How does a panel test look for these genes?
- The words you will meet, in plain language
- What does each result usually change?
- What this page cannot tell you
- Four things families assume, and what is actually true
- Common questions about HBOC genes beyond BRCA
The short answer
Which genes besides BRCA1 and BRCA2 can cause HBOC?
Several. PALB2 is the most important, with a breast cancer risk that comes closest to BRCA. ATM, CHEK2 and BARD1 raise breast cancer risk more moderately. RAD51C, RAD51D and BRIP1 mainly raise ovarian cancer risk. A few rarer syndromes also include breast or ovarian cancer.
Not every gene carries the same weight
Doctors sort these genes by how much they raise risk. A high-risk gene changes care a great deal, much as BRCA does. A moderate-risk gene raises risk less, and what it means depends heavily on the rest of the family history. Knowing which group a gene sits in matters more than knowing its name.
Why a BRCA-only test can miss the answer
Older tests often looked at BRCA1 and BRCA2 alone. A family with a clear pattern of breast or ovarian cancer and a negative BRCA result may still carry a fault in another gene. Today most laboratories test a panel of genes together, from one blood sample, so these are checked at the same time.
More genes also means more uncertain results
Every extra gene tested is another place to find a spelling change nobody can yet classify. That is the trade-off of a bigger panel, and a counsellor helps choose one that fits the family.
A negative BRCA result from years ago may be worth a second look. Ask your counsellor whether a wider test would add anything.The genes, grouped
What does each of these genes do to risk?
These are broad groups. The exact risk depends on the gene, the specific fault and the family.
PALB2: the closest to BRCA
PALB2 works alongside BRCA2 in repairing DNA. A fault raises breast cancer risk substantially, enough that care often looks similar to BRCA. It also modestly raises the risk of pancreatic and ovarian cancer, and of breast cancer in men.
ATM, CHEK2 and BARD1: moderate breast risk
These raise breast cancer risk above average but well below BRCA. Care is shaped by the gene and the family history together.
Also worth knowing
- ATM is linked to pancreatic and prostate cancer too
- CHEK2 is linked to some other cancers, including prostate
- Evidence on BARD1 is still growing
RAD51C, RAD51D and BRIP1: mainly ovarian
These raise ovarian cancer risk more than breast cancer risk. Because ovarian cancer cannot be reliably screened for, a result usually leads to a discussion about removing the tubes and ovaries at the right time.
Rarer syndromes that include breast or ovarian cancer
TP53, PTEN, CDH1 and STK11 cause wider syndromes in which breast cancer is one of several risks. The Lynch syndrome genes raise the risk of ovarian and womb cancer alongside bowel cancer. Each has its own pattern and its own plan.
Not sure whether this applies to you?
Ask an oncologistHow it is found
How does a panel test look for these genes?
The right person is tested first
Where possible, the relative who had breast or ovarian cancer gives a blood or saliva sample. Their result tells the family which gene, if any, to look for.
The counsellor chooses the panel
A focused panel covers the genes that fit the family pattern. A wider one covers more, and finds more uncertain results. The choice is made before the sample is sent, not after.
Each gene gets its own answer
The report lists any fault found, any variant of uncertain significance, and the genes that were clear. One report can say several different things at once.
The result is read against the family
A moderate-risk fault in a family with many young cancers means something different from the same fault in a family with none. This is why a counsellor, not the report, gives the final advice.
On your report
The words you will meet, in plain language
- Multigene panel
- A single test that looks at a set of cancer-related genes together, instead of one gene at a time.
- High-risk gene
- A gene where a fault raises cancer risk a great deal, enough to change care on its own. BRCA1, BRCA2 and PALB2 are examples.
- Moderate-risk gene
- A gene where a fault raises risk less. Care depends on the fault and the family history taken together.
- Penetrance
- How often a fault actually leads to cancer across everyone who carries it. It is never all of them.
- Variant of uncertain significance
- Often shortened to VUS. A spelling change the laboratory cannot yet call harmful or harmless. It should not change your care.
- Germline
- Present in every cell from birth and able to pass to children. This page is only about germline faults.
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Gene by gene
What does each result usually change?
The gene
What it usually changes
PALB2
Breast checks much like BRCA, with pancreatic checks in some families
ATM or CHEK2
Earlier or closer breast checks, shaped by the family history
BARD1
Earlier breast checks, with advice still being refined
RAD51C, RAD51D or BRIP1
A discussion about removing the tubes and ovaries, usually later than for BRCA1
A Lynch syndrome gene
Bowel and womb checks, and a discussion about the ovaries
Being straight with you
What this page cannot tell you
It cannot tell you what your own result means. Risk estimates for the moderate genes vary between studies, and most of those studies were done in families of European ancestry. Indian data is still small. What your specific variant means is a question for the counsellor who ordered the test.
It cannot say whether you need a wider test
That depends on which genes were covered before, who in the family was tested, and how strong the family pattern is. A counsellor can compare your old report with current panels and tell you whether retesting would add anything.
Tumour testing is a separate question
This page is about inherited faults found in blood. Faults found only inside a tumour guide treatment and are covered in the targeted therapy section of this site.
Who this does not apply to
Most people with one older relative with breast cancer do not need a panel test at all. Panels are for families with a pattern, or for people whose own cancer has features that point to an inherited cause.
Commonly believed
Four things families assume, and what is actually true
"My BRCA test was negative, so our cancers are not inherited."
It rules out BRCA faults, not every inherited cause. If the test looked at BRCA alone, another gene may still explain the family pattern.
"The more genes a test covers, the better."
Bigger panels find more uncertain results that can cause worry and no benefit. The best panel is the one that fits the family, not the longest one.
"Any gene fault means the same surgery as BRCA."
Preventive surgery is weighed very differently for a moderate-risk gene. For many of these genes, closer checks are the usual advice, and surgery is not recommended on the gene result alone.
"If I tested negative for the family's CHEK2 fault, I need nothing extra."
With moderate genes, the family history still counts. A relative who tests negative may still be advised extra checks because of who else in the family had cancer.
Questions we are asked
Common questions about HBOC genes beyond BRCA
My BRCA test was negative years ago. Should I test again?
Possibly. If the old test covered only BRCA1 and BRCA2, and the family pattern is strong, a panel may find an answer. Bring the old report to a counsellor, who can check exactly what was covered.
Is PALB2 as serious as BRCA?
For breast cancer, PALB2 comes close to BRCA2 and is managed in a similar way. Its ovarian risk is lower than BRCA. Your counsellor will explain how your family history adjusts that picture.
What does a moderate-risk result mean for me?
Your risk is higher than average but lower than with BRCA. It usually means earlier or closer breast checks. How much closer depends on who else in your family has had cancer, which is why it needs a counsellor to interpret.
Why did my panel find a VUS?
Every gene tested adds a chance of finding a change nobody can yet classify. A VUS is not a positive result. It should not change your treatment or lead to surgery, and it may be reclassified as evidence grows.
Do these genes affect men too?
Yes. Men can carry and pass on any of them. PALB2 raises the risk of male breast and pancreatic cancer. ATM and CHEK2 are linked to prostate cancer. Men in the family should be part of testing.
Can these results change cancer treatment?
Sometimes. PALB2 faults may open up some of the same medicines used for BRCA, though the evidence is smaller. For most moderate genes, treatment is planned on the tumour itself. Your oncologist will say whether your result matters.
Should my relatives be tested for the same fault?
Usually yes, for high-risk and moderate-risk genes alike. A relative's result is read together with the family history, so a negative test does not always mean ordinary screening. The counsellor will explain what each result means.
Does it matter if both parents carry a fault in the same gene?
For a few of these genes, such as ATM and PALB2, a child who inherits two faulty copies can have a rare and serious childhood condition. This matters more in families where parents are related. A counsellor can advise before pregnancy.
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
- National Cancer Institute — Genetics of Breast and Gynecologic Cancers (PDQ®)–Health Professional Version
- MedlinePlus Genetics — PALB2 gene
- MedlinePlus Genetics — CHEK2 gene
- Cancer Research UK — Inherited genes and cancer types
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
Is PALB2 as serious as BRCA?The one non-BRCA gene families ask about mostMultigene panel testingHow a panel works and how to choose oneA VUS in a germline reportWhat to do when a panel finds an uncertain changeHereditary breast and ovarian cancer syndrome explainedThe condition itself, before the genes
Talk to us
BRCA negative, but the family pattern is still there?
Bring your old report and a list of who in the family had cancer. We will help you work out whether a wider panel would add anything, and arrange counselling if it would. One helpline serves every CION centre.