Genes Associated with Hereditary Cancer

As science continues to evolve, so does our understanding of other genes that are associated with an increased risk of developing breast, ovarian and other cancers. The most commonly known genes associated with hereditary breast and ovarian cancer are the BRCA1 and BRCA2 genes however, there are several other mutations that have varying lifetime risk.

A genetic mutation in these genes can be inherited from either parent – mother or father.

Genetic Mutation Types

BRCA1

BRCA1 is a ‘cancer protection’ gene that helps to protect against breast, ovarian and prostate cancer. If you receive one either from your mother or father that isn’t working, it is called having a BRCA1 gene mutation. 

  • Women with a mutated BRCA1 gene have about a 70% chance of developing breast cancer and about a 45% chance of developing ovarian cancer over their lifetime.
  • Men have about a 9% chance of developing prostate cancer and about a 1% chance of developing breast cancer over their lifetime.  

Read more about the BRCA1 gene mutation at EVIQ

BRCA2

BRCA2 is also a ‘cancer protection’ gene that helps to protect against breast, ovarian, prostate and pancreatic cancer. If you receive one either from your mother or father that isn’t working, it’s called having a BRCA2 gene mutation. 

  • Women who have a mutated BRCA2 gene have about a 70% chance of developing breast cancer and about a 15% chance of developing ovarian cancer over their lifetime.
  • Men have about a 15% chance of developing prostate cancer and about a 7% chance of developing breast cancer over their lifetime.  
  • Men and women with a mutated BRCA2 gene have a less than 5% chance of developing pancreatic cancer over their lifetime.

Read more about the BRCA2 gene mutation at EVIQ

PALB2

Whilst BRCA1 and 2 are the most common of the genetic mutations that can raise the risk of breast and/or ovarian cancer, PALB2 is another mutation that can also result in an increased risk of breast cancer. It’s linked to breast cancer in men and women, and cancer of the pancreas in some families.  

If you receive a gene from your mother or father that isn’t working, it’s called a PALB2 gene mutation. 

  • Women who have a mutated PALB2 gene have about a 55% chance of developing breast cancer and about a 5% chance of developing ovarian cancer over their lifetime.
  • Men have a 1% chance of developing breast cancer over their lifetime.  
  • Men and women with a mutated PALB2 gene have about a 3% chance of developing pancreatic cancer over their lifetime.

Read more about the PALB2 gene mutation at EVIQ

BRIP1

BRIP1 is another ‘cancer protection’ gene. It can help protect against ovarian cancer and you can receive one either from your mother or father. When one of these genes isn’t working, it’s called a BRIP1 gene mutation. 

  • Women who have a mutated BRIP1 gene have about a 6% chance of developing ovarian cancer over their lifetime.

Read more about the BRIP1 gene mutation at EVIQ

ATM

The ATM gene can help protect against breast cancer and pancreatic cancer. When you receive a mutated ATM gene from your mother or father, it’s associated with an increased risk of these cancers. 

  • Women who have a mutated c.7271T>G ATM gene have about a 50% chance of developing breast cancer over their lifetime.
  • Both men and women with the c.7271T>G ATM gene mutation may also have an increased risk of developing pancreatic cancer. 

Read more about the ATM gene mutation at EVIQ

RAD51C

RAD51C is a ‘cancer protection’ gene that helps to protect against ovarian and breast cancer. Everyone has two RAD51C genes (one from their mother, and one from their father). If one gene isn’t working, this is known as having a RAD51C mutation.

  • Women who have a mutated RAD51C gene have about a 10% chance of developing ovarian cancer over their lifetime.
  • Women who have a mutated RAD51C gene have about a 20% chance of developing breast cancer over their lifetime. However, the chance of developing breast cancer may be higher or lower, depending on their family history of breast cancer. 

Read more about the RAD51C gene mutation at EVIQ

RAD51D

RAD51D is a ‘cancer protection’ gene that helps to protect against ovarian and breast cancer. Everyone has two RAD51D genes (one from their mother, and one from their father). If one gene isn’t working, this is known as having a faulty RAD51D gene, or having a RAD51D mutation.

  • Women with a mutated RAD51D gene have about a 10% chance of developing ovarian cancer over their lifetime.
  • Women with a mutated RAD51D gene, have about a 20% chance of developing breast cancer over their lifetime. However, the chance of developing breast cancer may be higher or lower, depending on their family history of breast cancer. 

Read more about the RAD51D gene mutation at EVIQ

CDH1 (Hereditary Diffuse Gastric Cancer Syndrome)

Genetic testing can reveal a mutation known as CDH1. This mutation is associated with hereditary diffuse gastric cancer syndrome, which is known to increase the risk of stomach cancer along with breast cancer in women.

When there is a family history of stomach cancer:

  • Women with a mutated CDH1 gene have about a 30% chance of developing stomach cancer and about a 40% chance of developing breast cancer over their lifetime.
  • Men with a mutated CDH1 gene have about a 40% chance of developing stomach cancer over their lifetime.

The chance of stomach cancer in a person with a mutated  CDH1 gene and no family history of stomach cancer isn’t clear.

Read more about the CDH1 gene mutation at EVIQ

CHEK2 (Checkpoint Kinase 2)

CHEK2 is a “moderate risk” cancer predisposition gene. Women with certain mutations in the CHEK2 gene have an increased lifetime risk of breast cancer. These moderate risk genes work with other genetic variants and environmental factors so the cancer risk isn’t as clear as for higher risk genes. 

 It may also be related to cancers of the lung, colon, papillary thyroid, prostate, and testicular germ cell tumours however, research is conflicting. 

  • Women with a mutated CHEK2 gene have about a 29% chance of developing breast cancer.

Read more about the CHEK2 gene mutation at EVIQ

NBN

Several studies have shown that people who inherit a mutated copy of NBN from one parent are at an increased risk of female breast or male prostate cancer. Ongoing research is still being done to better understand the associated cancer risks and subsequent treatment options for patients.

NF1

Genetic testing can find mutations in a gene called Neurofibromatosis type 1 (NF1). The NF1 gene is a ‘tumour protection’ gene that helps to protect against benign and malignant tumours. 

  • Women with NF1 mutation have about a 20% chance of developing breast cancer over their lifetime.
  • Women and men with NF1 also have an increased risk of developing other cancers including cancer of the nerve coverings, cancer of the nerves behind the eyes, a gastrointestinal stromal tumour or tumour of the adrenal gland. 

Read more about the NF1 gene mutation at EVIQ

PTEN (Cowden Syndrome)

PTEN is a tumour protection gene that helps to protect against benign and malignant tumours. When a person has a mutated PTEN gene, they’re known to have Cowden Syndrome which is part of the PTEN Hamartoma syndrome.

  • Women with PTEN Hamartoma syndrome have a greater than 30% chance of developing breast cancer and a greater than 10% chance of developing uterine cancer over their lifetime.
  • Men and women with PTEN Hamartoma syndrome have a greater than 10% chance of developing thyroid cancer and at least a 10% chance of developing kidney cancer over their lifetime.
  • People with PTEN Hamartoma syndrome also have an increased chance of developing bowel polyps and benign growths in the thyroid, breast, uterus, skin, mouth and brain.
  • Children with PTEN Hamartoma syndrome may have an increased chance of autism.

Read more about the PTEN gene mutation at EVIQ

SKT11

Inherited mutations in the SKT11 gene are associated with Peutz-Jeghers syndrome (PJS), a rare disorder that leads to an increased risk of noncancerous growths and increased risk of certain cancers.

  • Women with PJS have about a 45% chance of developing breast cancer and about a 20% chance of developing cervical cancer or ovarian cancer over their lifetime.
  • Both men and women with PJS have about a 40% chance of developing cancer of the large bowel, a 15% chance of developing cancer of the small bowel, a 30% chance of developing stomach (gastric) cancer and about a 25% chance of developing pancreatic cancer over their lifetime.
  • Males with PJS have an increased chance of developing testicular tumours in childhood and adolescence.

Read more about Peutz-Jeghers Syndrome at EVIQ

TP53 (Li-Fraumeni Syndrome)

Li-Fraumeni syndrome is a rare hereditary cancer syndrome associated with inherited mutations in the TP53 gene, sometimes referred to as P53. Li-Fraumeni syndrome is associated with several different young-onset cancers. People with traditional Li-Fraumeni syndrome have up to a 95% risk of developing cancer by age 60 and are also at risk for developing various different cancers over their lifetimes.

  • Women with a mutated TP53 gene have about an 85% chance of developing breast cancer over their lifetime.
  • Children with a mutated TP53 gene have an increased chance of developing soft tissue sarcoma, bone sarcoma, brain cancer, cancer of the adrenal gland, leukaemia, Wilms tumour, neuroblastoma, lung, bowel, stomach and pancreatic cancer before age 20 years.
  • Men and women with a mutated TP53 gene have increased risk of developing soft tissue sarcoma, bone sarcoma, brain cancer, bowel cancer, gastric (stomach) cancer and cancer of the adrenal gland, lung, prostate, kidney, pancreas and melanoma over their lifetime.

Read more about Li-Fraumeni Syndrome at EVIQ

Lynch syndrome (MLH1, MSH2, MSH6, PMS2, or EPCAM)

Lynch syndrome (also sometimes called hereditary nonpolyposis colorectal cancer, or HNPCC) is hereditary and affects 1 in 500-1,000 people.

Inherited mutations in the MLH1, MSH2, MSH6, PMS2 genes, or certain mutations in the EPCAM gene are associated with Lynch syndrome.

  • Women with a mutated MLH1 gene have about a 10% chance of developing ovarian cancer over their lifetime.
  • Women with a mutated MSH2 gene have about a 15% chance of developing ovarian cancer over their lifetime.
  • Women with a mutated MSH6 gene have a slightly increased chance of developing ovarian cancer over their lifetime.
  • Women with Lynch Syndrome can also be at higher risk for developing uterine cancer.
  • Women and men with Lynch syndrome can also be at a higher risk of developing bowel cancer or stomach cancer. 

Read more about Lynch syndrome at EVIQ

What do I do if I have a gene mutation?

If you think your family may be a carrier of a genetic mutation, please connect with our genetic counsellor service here. If you’re unfamiliar with the role of a genetic counsellor, you can learn more here.

If you have a gene mutation, it doesn’t mean you will develop cancer. You should talk to your doctor about ways you can minimise your risk including medication, breast or ovarian surgery and lifestyle changes.

References and more information