Inherited genes and cancer types

• Most cancers are not linked to inherited gene changes.

• If you have an inherited gene change it increases your risk of developing certain types of cancer.

• Some gene changes increase the risk of more than one cancer type.

Most cancers are not linked to inherited gene changes (mutations). Up to 12 in every 100 cancers (up to 12%) diagnosed are linked to an inherited gene change.

A gene change or mutation is a permanent change in the DNA that makes up a gene. This can be inherited from a parent.

Changes can also happen during your lifetime. For example too much ultraviolet (UV) radiation from the sun can damage DNA in your skin cells and cause skin cancer. This is an environmental factor not an inherited change.

You may also hear these gene changes called other terms such as gene:

• alterations

• variants

• faults

This information is about some of the inherited gene changes that can increase your risk of developing cancer.

It’s important to remember that these conditions are rare. Most cancers develop because of a combination of chance and our environment, not because we have inherited a cancer gene change.

Talk to your GP if you have a strong family history of cancer. Or if you think you could have inherited any of these gene changes.

BRCA1 and BRCA2 genes

Everyone has BRCA1 and BRCA2 genes. BRCA stands for BReast CAncer gene. They are important genes that stop the cells in our body from growing and dividing out of control. Doctors call these tumour suppressor genes.

A gene change in the BRCA1 or BRCA2 gene means that the cells can grow out of control. This can lead to cancer developing.

Changes to BRCA1 and BRCA2 genes are uncommon. Only around 1 in every 400 people have a change in the BRCA1 or BRCA2 gene.

Your ethnicity can also affect your risk of carrying BRCA1 or BRCA2 gene changes. For example 1 in 40 people who are of Ashkenazi Jewish ethnicity have a chance of carrying the BRAC1 or BRCA2 gene change.

Both men and women can have a changes to BRCA1 or BRCA2 genes. People who inherit versions of these genes with changes have an increased risk of developing different types of cancers. This includes:

• breast cancer

• ovarian cancer

• prostate cancer

• pancreatic cancer

Breast cancer

Researchers think that around 70 in every 100 women (around 70%) with a change in the BRCA1 or BRCA2 gene will develop breast cancer by the age of 80.

Less than 10 in every 100 men (less than 10%) with a change in the BRCA2 gene will develop breast cancer.

Ovarian cancer

Almost 45 in every 100 people (almost 45%) with a change in the BRCA1 gene will develop ovarian cancer by the age of 80. This compares to almost 20 in every 100 people (almost 20%) with a change in the BRCA2 gene.

Prostate and pancreatic cancer

Gene mutations in the BRCA1 and BRCA2 genes can also increase your risk of developing prostate and pancreatic cancer. But this risk is lower than the risk of developing breast or ovarian cancer.

Lynch syndrome

Lynch syndrome used to be called hereditary non polyposis colon cancer (HNPCC). It is caused by changes in the following genes:

• MLH1

• MSH2

• MSH6

• PMS2

• EPCAM

People with Lynch syndrome have an increased risk of developing bowel cancer. Your risk depends on which gene change you have and your gender. This means that over their lifetime:

• more than 50 in 100 women (more than 50%) with Lynch syndrome are diagnosed with bowel cancer

• around 70 in 100 men (around 70%) are diagnosed with bowel cancer

Most people with Lynch syndrome develop bowel cancer at a younger age compared with people who develop bowel cancer and don’t have Lynch syndrome.

Lynch syndrome can also increase your risk of developing other types of cancers. This includes:

• womb cancer

• ovarian cancer

• stomach cancer

• gallbladder cancer

• prostate cancer

• cancer of the urinary tract such as bladder cancer

• brain cancer

Li-Fraumeni syndrome (LFS)

Li-Fraumeni syndrome is caused by a change in the TP53 gene. The TP53 gene controls when a cell divides. It is called a tumour suppressor gene.

People with Li-Fraumeni syndrome have an increased risk of developing a number of cancers. The most common being breast cancer. Other possible cancers include:

• bone cancer

• a type of leukaemia called acute myeloid leukaemia (AML)

• soft tissue sarcoma

• brain tumours

• cancer of the adrenal gland

PTEN Hamartoma tumour syndrome

This syndrome includes Cowden syndrome. It is caused by a change in the PTEN gene. This syndrome increases your risk of developing benign tumours and different types of cancers. This includes:

• breast cancer

• thyroid cancer

• womb cancer

• bowel cancer

• kidney cancer

• melanoma skin cancer

Familial adenomatous polyposis (FAP)

FAP is caused by a change in the APC gene. It is a rare disease. Less than 1 in every 100 bowel cancers (less than 1%) diagnosed have a link to FAP. A change in the APC gene can cause hundreds of non cancerous (benign) growths called polyps to develop in the bowel. There are 2 types. The types are:

• classical familial adenomatous polyposis (FAP)

• attenuated familial adenomatous polyposis (AFAP)

People with classical FAP have hundreds of polyps. Some people may have thousands of polyps. These are usually picked up in young people in their teens and twenties. People with classical FAP will almost certainly develop bowel cancer by the age of 45 if they don’t have treatment.

People with AFAP have a milder form of the syndrome. So they have less polyps present. They usually appear at a later age. The risk of developing cancer is less than with classical FAP at around 7 out of 10 (around 70%).

People with FAP also have an increased risk of developing:

• stomach cancer

• thyroid cancer

• small bowel (duodenal) cancer

• pancreatic cancer

• liver cancer

MUTYH associated polyposis (MAP)

MAP is caused by changes in the MUTYH gene. To have MAP, a person needs to have 2 MUTYH genes with gene alterations, 1 from each parent.

People with MAP develop polyps and are likely to develop these in the large bowel (colon) and back passage (rectum). But polyps can also develop in the stomach and small bowel but this is less likely.

If you have MAP you have an increased risk of developing bowel cancer under 60 years of age.

People with only 1 MUTYH gene have a similar risk of developing bowel cancer as the general population.

Peutz Jeghers syndrome (PJS)

Peutz Jeghers syndrome is caused by a change in the STK11 gene. Some signs of PJS can appear during childhood. It includes darker skin around the mouth, lips, fingers and toes. Some people also have freckling around and inside the mouth.

People with PJS have an increased risk of developing:

• breast cancer

• bowel cancer

• pancreatic cancer

• stomach cancer

• ovarian cancer

Juvenile Polyposis syndrome (JPS)

JPS is linked to the BMPR1A and SMAD4 genes. A change in one of these genes can cause polyps to develop. This happens mostly in the large bowel (colon) and back passage (rectum). Polyps can also develop in the stomach and small bowel. Juvenile is the name of the type of polyp and is not related to the age at which people develop the polyps.

People with JPS have an increased risk of developing:

• stomach

• bowel cancer

• pancreatic cancer

• small bowel cancer

PALB2 gene

Faults in the PALB2 gene increase the risk of developing cancer of the breast, pancreas and ovary.

Almost 45 in every 100 women (almost 45%) with a faulty PALB2 gene will develop breast cancer by the age of 80.

Von Hippel-Lindau disease (VHL)

VHL is a rare inherited condition caused by a change in the von Hippel-Lindau gene. It can cause cancerous (malignant) and non cancerous (benign) tumours affecting different parts of the body. People with VHL can also have abnormal collections of blood vessels in the brain, spine and back of the eye.

Most tumours that develop with VHL are benign. But some people who have this condition have an increased risk of developing:

• pancreatic neuroendocrine tumours (pNETs)

• a type of kidney cancer called renal cell carcinoma

Tuberous sclerosis (TS)

Tuberous sclerosis is a rare condition caused by changes in the TSC1 and TSC2 genes. It can cause problems with the lungs, eyes, skin, brain, heart, and kidneys. It can also slightly increase your risk of developing a type of kidney cancer. This is called renal cell carcinoma.

Birt-Hogg-Dube syndrome (BHDS)

Birt-Hogg-Dube syndrome is caused by changes in the FLCN gene. People with BHDS often develop multiple benign skin tumours (fibrofolliculomas) and cysts. The most common areas for these to develop on are the scalp, face, neck and upper body.

First symptoms of BHDS for some people could be shortness of breath and chest pain. This is because cysts have grown in the lung causing it to collapse (pneumothorax). This is common in young adults.

Having BHDS can increase your risk of developing certain types of kidney cancer.

Researchers think that BHDS may also increase your risk of bowel cancer. But they need more research to find out for sure.

Multiple endocrine neoplasia (MEN) type 1 and 2

MEN is a rare inherited condition in which tumours develop in different parts of the body. There are 2 types, MEN1 and MEN2.

People with MEN1 usually develop tumours in the pancreas, parathyroid gland Open a glossary item and pituitary gland Open a glossary item. Less commonly tumours can also develop in the:

• adrenal glands

• small bowel

• stomach

• thymus

• lungs

The tumours can be non cancerous (benign) or cancerous (malignant).

MEN2 is caused by a change in the RET gene. Nearly everyone with MEN2 develop a type of thyroid cancer called medullary thyroid cancer. MEN2 also increases your risk of developing tumours of the adrenal gland and parathyroid gland.

RB1 gene

A fault in the RB1 gene can increase your risk of developing a rare type of eye cancer called retinoblastoma. Retinoblastoma most commonly affects children under the age of 5. It can affect one or both eyes.

Familial atypical multiple mole melanoma syndrome (FAMMM)

FAMMM is a syndrome that increases your risk of developing melanoma skin cancer. People with FAMMM tend to have large numbers of moles or moles that are unusual. They also have at least one first degree relative or second degree relative with a diagnosis of melanoma.

FAMMM syndrome can also increase your risk of developing pancreatic cancer.

Hereditary kidney cancer syndromes

Hereditary papillary cancer is linked with a high risk of developing kidney cancer. There are different syndromes including:

• hereditary papillary renal cell carcinoma (HPRC)

• hereditary leiomyomatosis and renal cell cancer (HLRCC)

HLRCC is also known as Fumarate Hydratase Tumor Predisposition Syndrome (FHTPS).

HPRC is caused by a change in the MET gene. People with HPRCC usually have more than one tumour in both kidneys.

HLRCC is caused by a change in the FH gene and it causes:

• benign skin tumours called cutaneous leiomyomata

• fibroids in the womb or uterine leiomyomata

• kidney cancer

CHEK2 gene

The CHEK2 gene helps to repair DNA. A change in the CHEK2 gene can increase your risk of developing breast cancer. People with a CHEK2 change have a 25 to 30 in 100 (25% to 30%) chance of developing breast cancer in their lifetime.

CHEK2 gene change can also increase your risk of developing other cancers including:

• prostate cancer

• kidney cancer

• thyroid cancer

• large bowel (colon) cancer

There are other hereditary genes that can increase a person’s risk of developing cancer including:

• RAD51

• ATM

There is more information about specific genes that can increase your risk of a particular cancer in our risks and causes information for each cancer type.

Seeing your GP

Talk to your GP if you think you could have inherited any of these gene changes. Or if you have a strong family history of cancer. A strong family history of cancer means multiple close family members on the same side of the family who have the same cancer or related cancer types.

Your GP can refer you to a genetic clinic where you will see a genetic counsellor or genetic doctor. They can look into your family history and offer you genetic testing.

Read about genetic testing for cancer risk

Find out more

Family history and inherited cancer genes

Genetic testing for cancer risk

Getting your genetic test results