Family history and genetics

Having a family history of endometrial cancer, or a family history of colorectal cancer in families with Lynch syndrome, is associated with an increased risk of endometrial cancer. 

Affected relatives could be on either the father’s or mother’s side of the family.

For some women, the fact that other members of the family may have one or more of these cancers may be due to chance. However, some women with a family history may have inherited a faulty gene that increases the risk of cancer. Sometimes there is a fault, or mutation, in one copy of a gene. This can stop the gene from working properly and can lead to an increased risk of endometrial cancer.

It may be appropriate for some women who have a strong family history to be referred to a family cancer clinic. Family cancer clinics can help assess risk, provide advice about genetic testing, and recommend an individualised management plan.

For more information on the Cancer Australia website, please visit Family Cancer Clinics.

Mismatch repair gene mutations (Lynch syndrome)

There is convincing evidence that having a fault in a mismatch repair (MMR) gene, known as Lynch syndrome, is associated with an increased risk of endometrial cancer.

The size of the risk of developing endometrial cancer in someone with Lynch syndrome depends on which MMR gene is affected. Overall, about 1 in 3 women with Lynch syndrome will develop endometrial cancer.

Lynch syndrome is an inherited condition that increases a person’s risk of developing certain types of cancer. When a person has Lynch syndrome, it means that one or more genes involved in repairing DNA does not work properly. The genes involved in Lynch syndrome are called ‘mismatch repair (MMR) genes’. There are four of these genes: MLH1, MSH2, MSH6, and PMS2. Lynch syndrome can occur when any one of these genes is faulty.

When MMR genes do not work properly, DNA damage can build up in cells of the body, including cells in the uterus. If the DNA damage is not repaired, the cells can start to grow and divide in an uncontrolled way. This can lead to cancer, including endometrial cancer.

Further information can be found at:

• Cancer Australia information on Lynch syndrome.

PTEN gene mutation (Cowden syndrome)

There is convincing evidence that having a fault in the PTEN gene as part of Cowden syndrome is associated with an increased risk of endometrial cancer.

Around 1 in 4 women who have a PTEN gene fault are likely to develop endometrial cancer by the age of 70 years.

Cowden syndrome is a rare inherited condition that is associated with some benign (non-cancerous) growths in different parts of the body. It is also associated with an increased risk of some types of cancer, including endometrial cancer. Cowden syndrome is one of the disorders caused by a fault in the PTEN gene.

The PTEN gene is involved in controlling the way in which cells divide and grow. If the PTEN gene is not working properly, cells can grow and divide in an uncontrolled way. This includes cells in the uterus. Uncontrolled growth of cells in the uterus and can lead to development of endometrial cancer

Family history of endometrial cancer or colorectal cancer

There is convincing evidence that a family history of endometrial cancer is associated with an increased risk of endometrial cancer. A family history of colorectal cancer and Lynch syndrome  is also associated with an increased risk of endometrial cancer.

Studies have looked at the risk of endometrial cancer in women who have a first degree relative (mother, sister, daughter) who has (or had) endometrial cancer. Around 3 in 100 women (3.1%) who have an affected first degree relative will develop endometrial cancer compared with just under 2 in 100 women (1.8%) who do not have an affected first degree relative.

The risk of endometrial cancer is also slightly higher (about 1.2 times higher) for women who have a first degree relative (mother, father, sister, brother, daughter, son) who has (or had) colorectal cancer compared with women without a family history of colorectal cancer.  This increase in risk is only seen if the family also has Lynch syndrome.

Current evidence suggests that only a small number of cases of endometrial cancer are due to family history. A family history may be due to genetic changes that lead to a higher likelihood of developing endometrial cancer. In addition, family members often have similar environments and lifestyles as each other. These shared backgrounds could also contribute to the increased endometrial cancer risk in women with a family history of endometrial cancer.

Further information can be found at:

• Cancer Australia information on Lynch syndrome.