Inherited Cancers Australia

I want to know more about gene mutations related to cancer

You can’t choose your genes, but you can learn more from them.

In our bodies, there are cancer protection genes. A change in these genes may be described as a ‘gene mutation’, ‘gene fault’, ‘gene change’ or ‘pathogenic variant’. The terms are often used interchangeably.

It’s believed about 5% to 10% of cancers are because of inherited genetic factors, including gene mutations, or faults. A mutation is a change in the DNA sequence of a gene that stops the gene functioning as it should. Clinically significant mutations can increase a person’s lifetime risk of cancer.

The most commonly known gene mutations related to cancer are found in the BRCA1 and BRCA2 genes, however, many other gene mutations can cause cancer. These gene mutations can be inherited from your mother or father. It is important to highlight that your chance of inheriting a gene mutation associated with cancer isn’t 100%. For example, if one of your mother’s BRCA1 genes has a mutation and her other BRCA1 gene is “normal” and doesn’t have a mutation, there’s a 50% chance you’ll inherit the mutation and a 50% chance you won’t.

Having a gene mutation does not mean you will definitely develop cancer. It means that you have an increased risk of developing certain types of cancers. Depending on the gene mutation, the type and risk of cancer can vary among people, even within the same family.

It is important to note that cancer risks are estimates over the course of a person's lifetime. A person’s lifetime risk will vary depending on:

current age
sex assigned at birth
specific gene mutation
personal and family health history
diet, exercise, lifestyle and other factors

As science continues to evolve, so is our understanding of other genes that are associated with an increased risk of developing cancer.

Here are some of the common and rarer genes that have had mutations detected that are associated with the development of cancer:

BRCA1

BRCA1 is a ‘cancer protection’ gene that helps to protect against breast, ovarian and prostate cancer. If you receive a BRCA1 gene 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 20% chance of developing prostate cancer and about a 1% chance of developing breast cancer over their lifetime.
Both men and women with a faulty BRCA1 gene also have an increased chance of developing pancreatic cancer over their lifetime, but the exact chance is unknown.

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 25% chance of developing prostate cancer and about a 4% chance of developing breast cancer over their lifetime.

Both men and women with a faulty BRCA2 gene also have an increased chance of developing pancreatic cancer over their lifetime, but the exact chance is unknown.

PALB2

Whilst BRCA1 and 2 are the most common of the genetic mutations that can increase 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, ovarian cancer in 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 with a faulty PALB2 gene also have an increased chance of developing prostate cancer over their lifetime, but the exact chance is unknown.
Men and women with a mutated PALB2 gene have about a 3% chance of developing pancreatic cancer over their lifetime.

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.

ATM

The ATM gene can help protect against breast cancer, prostate 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. Women with a mutation elsewhere in the ATM gene also have increased risk of developing breast cancer, but this is a reduced risk of less than 30%.
Men with a faulty ATM gene have an increased chance of developing prostate cancer over their lifetime, but the exact chance is unknown.
Both men and women with an ATM gene mutation may also have an increased risk of developing pancreatic cancer.

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 RAD51C gene mutation 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

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.

CDH1 (Hereditary Diffuse Gastric Cancer Syndrome)

CDH1 is a ‘cancer protection’ gene that helps to protect against stomach and breast cancer.

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.

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.

Most women with a faulty CHEK2 gene have between 20% and 30% chance of developing breast cancer over their lifetime. The chance of developing breast cancer may be lower than 20% or higher than 30% for some women, if they have close relatives with breast cancer.
Your cancer risk may be different depending on the specific CHEK2 mutation you have. Most CHEK2 mutations increase your risk for breast cancer.
Some CHEK2 mutations slightly increase mens risk for colorectal (colon and rectal) and prostate cancer.

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.

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 an 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.

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 and men with Lynch syndrome can also be at a higher risk of developing bowel cancer or stomach cancer.
Women with a mutated MLH1 gene have about a 35% chance of developing endometrial cancer and 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.

Genetic mutations