Genes and Syndromes

1Inherited Cancer Syndromes and Germline Mutations

You can't inherit cancer but you can inherit an increased risk of cancer.

Hereditary syndromes are causes by germline mutations (spelling errors also known as pathogenic variants) in important genes. Germline mutations are present at birth and can be passed from a mother or a father to their child via the egg or the sperm. That is why they are called hereditary or familial cancer syndromes.

Hereditary cancer syndromes usually involve mutations in genes responsible for cell growth, DNA repair or quality assurance. These are very important genes and when they aren't working properly the risk of cancer is significantly increased and it may occur at a young age.

They are called syndromes because groups of cancers or problems may occur together and will be seen to be running in a family, affecting parents, children and cousins. In some families, the syndrome can be traced back over many generations.

Some Hereditary Cancer syndromes have a strong phenotype (a "look"), such as rare types of skin lesions. For others, we rely on the type of cancer, age of onset or just the number of cancers in a family

If you are concerned about your family’s history of cancer, download our Family History Questionnaire and discuss it with your doctor. Knowing about your risk means you can do something about it.

We've listed many Hereditary Cancer syndromes and the genes associated with them. Under each syndrome, click the "read more" link for a more in-depth description of what the increased risks may be, how to reduce that risk and also for a list of specific support groups or other resources.

We also have more information in our FAQ section on:

2Ataxia-Telangiectasia and the ATM gene

Ataxia Telangiectasia syndrome is a rare condition, affecting 1 in 40,000 to 100,000 people worldwide. It causes severe disability and is usually diagnosed in early childhood.

Ataxia-Telangiectasia syndrome occurs when an individual inherits mutations in the ATM gene from both their mother and their father (autosomal recessive).

When an individual inherits only one copy of the ATM gene with a mutation, Ataxia Telangiectasia syndrome doesn't occur. However, the lifetime risk of breast cancer is increased and, for one particular mutation, the lifetime risk of breast cancer is very high.

Read More

3BAP1 Tumour Predisposition syndrome and the BAP1 gene

BAP1 tumour predisposition syndrome is caused by mutation in the BAP1 gene. It is associated with melanocytic tumours, including melanoma, melanoma of the eye (uveal melanoma), malignant mesothelioma (a cancer of the lining of the chest cavity, usually associated with asbestos exposure), renal cell cancers (a type of kidney cancer) as well as basal cell carcinomas and atypical Spitz tumours.

Genetic testing for germline BAP1 mutations should be considered if there are two or more confirmed BAP1-associated tumours (excluding BCC or cutaneous melanoma).

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4Birt Hogg Dubé syndrome and the FLCN gene

Birt Hogg Dubé syndrome (BHD) is a inherited syndrome caused by a mutation (change in the DNA code) in the Folliculin gene (FLCN). It is very rare, with around 400 families known worldwide.

It is associated with a small lumps on the face and chest called fibrofolliculoma, cysts in the lungs and cysts and tumours, which may become cancer, in the kidneys.

The severity of the syndrome varies, even in the same family, and is not predictable but here's lots that can be done to reduce risk.

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5Cowden Syndrome, the PTEN Hamartoma Tumour syndromes and the PTEN gene

When there is a mutation (change in the DNA code) in the PTEN gene, the signs and symptoms that occur can vary greatly (even from individual to individual in the same family).

The best known syndrome of the PTEN related syndromes is Cowden syndrome. It affects 1:200,000 people.

Individuals with Cowden syndrome often have a large head ("macrocephaly"), almost always develop skin lesions such as trichilemmomas and lipomas. They also develop lumps (such as hamartomas) in the breast, thyroid or uterus and bowel polyps may be more common.

The risk of breast, uterine, thyroid and kidney cancer is increased in individuals with Cowden syndrome, but there's lots that can be done to reduce risk.

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6DICER1 syndrome and the DICER1 gene

DICER1 syndrome is associated with rare types of benign and malignant tumours that usually occur in childhood. The most frequently reported tumours are pleuropulmonary blastoma (PPB), cystic nephroma, multinodular goitre and certain rare types of ovarian tumours.

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7Familial Adenomatous Polyposis and the APC gene

Familial Adenomatous Polyposis (FAP), as the name suggests, causes polyps. It occurs when a mutation (change in the DNA code) of the growth gene APC result in the gene being permanently "switched on"

In the classic form, 100 to 1000s of polyps develop in the colon. Another, milder form also exists, called attenuated FAP. Here, 10s to 100s of polyps develop, usually appearing at a later age.

Left untreated these polyps almost always become cancerous but there's lots that can be done to reduce risk.

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8Fanconi Anaemia and Biallelic Mutations in Breast and Ovarian Cancer Risk Genes

Fanconi anaemia is a rare but serious syndrome. It is can be caused by inheriting a mutation in both copies of a BRCA or BRCA-related gene.

Fanconi anaemia results in bone marrow failure in childhood, requiring a bone marrow transplant. It also causes growth retardation, problems with the development of the thumb and/or forearm, a weakened immune system and other problems that may be detected at a very young age.

There are more than 20 genes known to cause Fanconi anaemia and they include BRCA1, BRCA2, BRIP1, PALB2 and RAD51C

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9Gastrointestinal Stromal tumours and the KIT and PDGFRA genes

Gastrointestinal stromal tumours (GIST) are abnormal growths (tumours) that arise in the supporting tissue (stroma). GIST occur mainly in the stomach and small intestine but can occur anywhere in the gastrointestinal tract.

GIST can run in families and are sometimes associated with other rare tumours such as paraganglioma and pheochromocytoma

Read More
10Gorlin or Basal Cell Carcinoma syndrome and the PTCH1 and SUFU genes

Gorlin syndrome is caused by a germline mutation in the PTCH gene and less commonly, the SUFU gene. It is rare, affecting around 1 in 30,000 people.

Individuals with Gorlin syndrome develop a type of skin cancer called basal cell carcinoma (BCCs)at a young age. BCCs are common, particular on sun damaged skin. However, some people with Gorlin syndrome develop thousands of BCC's.

The signs and symptoms of Gorlin syndrome vary greatly from individual to individual, even in the same family.

Read More
11Gardner syndrome

Gardner syndrome is a clinical syndrome used to describes families with multiple bowel polyps (adenomas of the colon) and/or colon cancers as well as skin lumps such as epidermoid cysts, lipomas and sebacceous adenomas as well as desmoids (tumour of the connective tissues) and osteomas (benign bone growths, often found in the jaw).

It's an old term, first used in the 1950s by Dr Eldon J Gardner.

It is no longer used as it is describes the clinical features of 2 hereditary cancer syndromes that have very different genetic causes and different cancer risks: Lynch syndrome and Familial Adenomatous Polyposis syndrome.

In Lynch syndrome, there may be only a few polyps and if skin lumps occur they are likely to be sebaceous adenomas. There is an increased risk of bowel (colon), uterine and ovarian cancer and the sebaceous adenomas can also develop into cancer (sebaceous adenocarcinomas). The combination of sebaceous adeoma and bowel cancers was also described by 2 other doctors and also used to be known as Muir-Torre syndrome. It it also an obsolete term.

In Familial Adenomatous Polyposis syndrome, hundreds or even thousands of polyps may occur in the bowel as well as elsewhere in the digestive tract and these can develop into cancer. The lumps tend to be desmoids, osteomas, epidermoid cysts and lipomas.

Read more about Lynch syndrome and Familial Adenomatous Polyposis syndrome.
12Hereditary Breast and Ovarian Cancer syndrome and the BRCA1 and BRCA2 genes

The BRCA1 and BRCA2 genes were the first genes identified as causing a very high risk of breast and ovarian cancer.

They are important for fixing the mistakes that occur in the DNA of cells. You can think of them as spell-checker genes.

If you carry a BRCA1 or BRCA2 mutation, the risk of certain cancers increases. If you know you are at increased risk, there is a lot you can do for yourself and your family

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13Other Hereditary Breast and/or Ovarian genes including ATM, CHEK2, BRIP1, PALB2, RAD51C and RAD51D

Many people know that mutations in the BRCA1 and BRCA2 genes increase breast and ovarian cancer risk. But they don't work alone.

Other moderate to high risk genes include ATM, BRIP1, PALB2, RAD51C and RAD51D.

Read More
14Hereditary Diffuse Gastric Cancer syndrome and the CDH1 gene

Germline mutations in the CDH1 gene cause an inherited cancer syndrome called Hereditary Diffuse Gastric Cancer syndrome. This syndrome is associated with a significantly increased risk of diffuse gastric cancer (up to 80% by age 80) and lobular breast cancer in women (up to 60% by age 80), with most of the cancers occurring before age 40.

It is very rare.

As this type of gastric cancer can spread (metastasise) when the cancer is microscopic, gastrectomy (removal of the stomach) is the only effective prevention.

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15Hereditary Leiomyomatosis and Renal Cell Cancer syndrome and the FH gene

We are still updating the information for this page. Please check back in a week or so.

16Hereditary Mixed Polyposis syndrome and the GREM1 gene

As the name suggests, Hereditary Mixed Polyposis syndrome results in an increased risk of a variety of different polyps in the bowel (colon) including adenoma, hyperplastic, hamartoma, juvenile and serrated.

Hereditary Mixed Polyposis syndrome is very rare, although a specific mutation in the GREM1 gene is found in almost 1% of individuals with Ashkenazi Jewish heritage.

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17Hereditary Ovarian Cancer syndrome and the BRIP1 gene

BRIP1 works with BRCA1 to fix DNA damage.

Mutations in BRIP1 are associated with increased risk of ovarian cancer and most guidelines recommend removing the ovaries and fallopian tubes around age 55, when the risk starts to rise

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18Hereditary Pancreatic Cancer and the STK11, BRCA2 and CDKN2A genes

Around 2500 Australians are diagnosed with pancreatic cancer each year. When 2 or more closely related blood relatives (such as parent; child or brothers and/or sisters) are diagnosed the term Familial Pancreatic Cancer is used.

Is some families, a germline (inherited) mutation (change in the DNA code) in a key gene is responsible. These genes include STK11 (associated with Peutz-Jeghers syndrome) BRCA2 (associated with hereditary breast and ovarian cancer syndrome), PRSS1 or SPINK1 (associated with Hereditary Pancreatitis) and CDKN2A (associated with Familial Atypical Multiple Mole Melanoma syndrome)

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19Hereditary Papillary Renal Carcinoma Type 1 syndrome and the MET gene

We are still updating the information for this page. Please check back in a week or so.

20Hereditary Paraganglioma Pheochromocytoma syndrome and the SDH genes

We are still updating the information for this page. Please check back in a week or so.

21Hereditary Prostate Cancer and the BRCA, PALB2 and HOXB13 genes

We are still updating the information for this page. Please check back in a week or so.

22Hereditary Testicular Cancer

Most testicular cancer is not hereditary. However, for a rare type of testicular cancer, called a sex cord stromal tumour, a mutation in the STK11 gene associated with Peutz Jeghers syndrome may be responsible

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23Hyperparathyroidism Jaw Tumour syndrome and the CDC73 gene

We are still updating the information for this page. Please check back in a week or so.

24Juvenile Polyposis syndrome and the SMAD4 and BMPR1A genes

We are still updating the information for this page. Please check back in a week or so.

25Li-Fraumeni syndrome and the TP53 gene

Li Fraumeni syndrome is a rare, inherited cancer syndrome caused by mutations affecting the TP53 gene. It is associated with a very high risk of cancer including soft tissue sarcoma, osteosarcoma, premenopausal breast cancer, brain tumours, adrenocortical carcinomas and leukaemia. These cancers may occur in childhood or young adulthood.

Li Fraumeni syndrome can't be cured. Management focuses on early diagnosis through screening, which starts at a young age, and sometimes surgery.

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26Lynch syndrome, HNPCC and the MLH1, MSH2, MSH6 and PMS2 genes

Lynch syndrome affects between 1:600 and 1:2000 people and is responsible for 3 to 5% of bowel and uterine cancers. Lynch syndrome is caused by mutations (changes in the DNA code) that affect one of the 4 Lynch syndrome genes.

The Lynch syndrome genes are also known at the mismatch repair genes because of their role in fixing mistakes that occur in the DNA of dividing cells.

Lynch syndrome is associated with a high risk of colon, uterine and ovarian cancer but there is a lot that can be done to reduce that risk.

Read More
27Malignant Melanoma and the CDKN2A gene

In Australia, melanoma is the 3rd most common cancer. It affects 1:18 people, mainly over age 60.

When many individuals in a family have been affected, the term Familial Malignant Melanoma syndrome is used. In some families, the risk is increased because of a mutation in a particularly gene, such as CDKN2A (other genes included CDK4, BAP1, POT1, ACD, TERF2IP and TERT).

These kind of inherited gene mutations are rare. However, affected families should have skin screening with dermoscopy, total-body photography and/or sequential digital dermoscopy imaging every 6 months.

Read More
28Muir-Torre syndrome

Muir-Torre syndrome is a clinical syndrome used to describes families with skin tumours such as keratoacanthomas and sebaceous adenocarcinomas who also have bowel (colon) and duodenal cancers.

It's an old term, and combines the names of the 2 doctors who described the clinical syndrome in the 1960s: Surgeon EG Muir and dermatologist D Torre.

It is no longer used. It describes the clinical features of a hereditary cancer syndrome now known to be caused by inherited mutations affecting the mismatch repair genes, Lynch syndrome.

While Lynch syndrome is associated with sebaceous adenocarcinomas in some families, it is the increased likelihood of colon, uterine and ovarian cancer that causes the greatest risk.

The combination of bowel cancers and sebaceous adenoma and other skin lumps was also described by another doctor and used to be known as Gardner syndrome. It is also an obsolete term.

Read more about Lynch syndrome
29Multiple Endocrine Neoplasia Type 1 and the MEN1 gene

We are still updating the information for this page. Please check back in a week or so.

30Multiple Endocrine Neoplasia Type 2 and the RET gene

We are still updating the information for this page. Please check back in a week or so.

31MUTYH Associated Polyposis and the MUTYH gene

MUTYH Associated Polyposis (MAP) syndrome affects 1 in 10,000 to 40,000 people. It is more common in people with European ancestry affecting 1 in 5,000 to 1 in 10,000 of this population.

MUTYH associated polyposis (MAP) results in a high risk of polyps and cancers affecting the stomach, small bowel and colon. This syndrome occurs ONLY if an individual inherits mutations (pathogenic variants) in the MUTYH gene from both their mother and their father.

Inhereting only one MUTYH mutation may result in small increase in bowel cancer risk.

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32Neurofibromatosis Type 1 and the NF1 gene

Neurofibromatosis Type 1 is a hereditary cancer syndrome caused by germline mutations in the NF1 gene. It affects 1 in 3,000 people to 1 in 4,000 people.

Neurofibromatosis type 1 (NF1) is characterised by multiple growth on the skin (neurofibroma).

Unlike many hereditary cancer syndromes in which a mistake in a gene has been passed down over many generations, in NF1, around half of the cases are caused by a new mistake ("de novo" mutation).

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33Neurofibromatosis Type 2 and the NF2 gene

Neurofibromatosis Type 2 is a hereditary cancer syndrome caused by germline mutations in the NF2 gene. It affects 1 in 33,000 people.

Neurofibromatosis type 2 (NF2) is characterised by growths affecting certain types of nerve cells resulting in meningioma, schwannoma, glioma and neurofibroma.

Unlike many hereditary cancer syndromes in which a mistake in a gene has been passed down over many generations, in NF2, around half of the cases are caused by a new mistake ("de novo" mutation).

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34Peutz Jeghers syndrome and the STK11 gene

Peutz Jeghers syndrome is a hereditary cancer syndrome caused by germline mutations in the STK11 gene.

Peutz Jeghers syndrome is characterised by polyps called hamartoma which occur in the digestive tract, especially the small and large intestines, and freckling (hypermelanotic spots) around the mouth as well as inside the mouth.

Individuals with Peutz Jeghers syndrome are at increased risk of cancer, particularly of the large and small intestine, stomach, pancreas, breast and ovary. These cancers can occur at a young age. Tumours which secrete oestrogen, involving the ovary or testes, can also occur.

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35Polymerase Proofreading Polyposis syndrome and the POLE and POLD1 genes

POLE and POLD1 are polymerase proof-reading genes. Their role is to fix mismatches that occur when DNA is copied. When they are damaged (mutated) there is an increased risk of polyps and colon (bowel) cancer as well as uterine cancer.

Polymerase Proofreading Polyposis syndrome is very rare but important to know about as it leads to a hypermuted tumour phenotype that has treatment implications.

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36Serrated Polyposis syndrome

Serrated Polyposis syndrome (SPS) is defined by the occurrence of multiple or large serrated polyps in the colon.

Serrated polyps are different from common adenomatous polyps, although these can also be present.

It is associated with a 15% to 35% lifetime risk of bowel (colorectal) cancer. Colonoscopy screening can reduce this risk to about 1%.

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37Turcot syndrome

Turcot syndrome is a clinical syndrome used to describe families with early onset of both bowel (colon) cancers and brain tumours.

It's an old term, first used in the 1950s by Mr Jacques Turcot, a surgeon. (Turcot is pronounced Tur coh, the "t" is silent).

It is no longer used as it is describes the clinical features of 2 hereditary cancer syndromes which are now know to have very different genetic causes and also different cancer risks. The syndromes are Lynch syndrome and Familial Adenomatous Polyposis syndrome.

In Lynch syndrome, there may be only a few bowel polyps but the lifetime risk of colon cancer is more than 30 or 40%. The brain tumours were usually glioblastoma. Lynch syndrome is also associated with high risk of uterine and ovarian cancer.

In Familial Adenomatous Polyposis syndrome, hundreds or even thousands of polyps may occur in the bowel from a very young age and the lifetime risk of colon cancer is 100% if nothing is done to reduce the risk. The brain tumours are usually medulloblastoma.

Read more about Lynch syndrome and Familial Adenomatous Polyposis syndrome.
38Von Hippel Lindau syndrome and the VHL gene

Von Hippel Lindau syndrome affects around 1 in 36,000 people. It is caused by a mutation in the VHL gene.

It is associated with an increased risk of certain growths called haemangioblastoma of the brain, spinal cord and retina and cysts affecting the kidney, pancreas and inner ear (endolymphatic sac tumours). Tumour may develop in the adrenal gland (pheochromocytoma) and these can secrete adrenalin and similar hormones.

Screening starts young to prevent the tumours causing problems such as deafness or becoming cancers

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