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.

Read More
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.

Read More
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.

Read More
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.

Read More
8Gastrointestinal 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
9Gorlin 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

10Gardner 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.
11Hereditary 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

Read More
12Other 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
13Hereditary 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.

Read More
14Hereditary 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.

15Hereditary Mixed Polyposis syndrome and the GREM1 gene

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16Hereditary Ovarian Cancer syndrome and the BRIP1 gene

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17Hereditary 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)

Read More
18Hereditary 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.

19Hereditary Paraganglioma Pheochromocytoma syndrome and the SDH genes

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20Hereditary Prostate Cancer and the BRCA, PALB2 and HOXB13 genes

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21Hereditary Testicular Cancer

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22Hyperparathyroidism Jaw Tumour syndrome and the CDC73 gene

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23Juvenile Polyposis syndrome and the SMAD4 and BMPR1A genes

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24Li-Fraumeni syndrome and the TP53 gene

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25Lynch syndrome, HNPCC and the MLH1, MSH2, MSH6 and PMS2 genes

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26Malignant 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
27Muir-Torre syndrome

Muir-Torre syndrome is a clinical syndrome used to describes families with skin tumours such as keratoacanthomas and sebaceous adenocarcinomas and other cancers specifically 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 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 adeoma 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
28Multiple Endocrine Neoplasia Type 1 and the MEN1 gene

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29Multiple Endocrine Neoplasia Type 2 and the RET gene

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30MUTYH Associated Polyposis and the MUTYH gene

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31Neurofibromatosis Type 1 and the NF1 gene

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32Neurofibromatosis Type 2 and the NF2 gene

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33Peutz Jeghers syndrome and the STK11 gene

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

34Polymerase 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 in DNA. When they are damaged (mutated) there is an increased risk of polyps and colon (bowel) cancer as well as uterine cancer.

It is very rare but important as it leads to a hypermuted tumour phenotype that has treatment implications.

Read More
35Serrated 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%.

Read More
36Turcot syndrome

Turcot syndrome is a clinical syndrome used to describe families with had 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 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 bowel polyps but the lifetime risk of colon cancer is more than 30 or 40%. . The brain tumours were usually glioblastoma.

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.
37Von 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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