Inherited genes and cancer types

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 and pituitary gland . 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.