Genetics:

Up to 20% of epithelial ovarian cancers may be hereditary, and run in families. Hereditary cancers are caused by inheriting a variant in a ‘cancer protection’ gene that stops it from working properly. You can inherit a gene variant from either your mother’s or father’s side of the family.

Many women who have ovarian cancer or who have a relative with ovarian cancer want to find out if the cancer may be hereditary. 

What are genes?

Genes are the instructions that tell our body’s cells what to do. Genes determine things like what colour hair and eyes we have and how tall we are. Genes are the recipe for all of the building blocks that make up our bodies. Humans have about 25,000 pairs of genes in every cell of our bodies. One copy of each pair of genes is inherited from each of our parents.

Sometimes changes happen in genes that can stop the gene from working properly. These changes are called a ‘pathogenic gene variant’ or ‘mutation’. In some cases, these gene variants can cause disease.

Ovarian cancer in the family:

Most people diagnosed with ovarian cancer do not have a history of ovarian cancer in their family. However, some people’s family history of ovarian cancer can increase their risk of developing the disease. Someone may have a family history just by chance, or it may be because there is a gene variant running in the family that increases the risk of developing cancer.

The family history on your father’s side is just as important as the history on your mother’s side. You are considered to have a strong family history of cancer if you have two or more close relatives on the same side of the family who have had cancer AND:

• These relatives have all had cancers that could be caused by the same gene (e.g. bowel, uterine and ovarian cancer, or breast and ovarian cancer), and they were diagnosed before age 50;
• OR You have a family member who has had a positive result on genetic testing, confirming they have a gene variant that increases cancer risk (e.g the BRCA1 or BRCA2 gene);
• OR You have Ashkenazi Jewish ancestry (specific BRCA variants are more common than in the general population);
• OR You have had cancer diagnosed at a young age, or you have had more than one type of cancer.

Inheriting an ovarian cancer gene:

Ovarian cancer caused by a gene variant running in a family is called ‘hereditary cancer’. Having a personal or family history of ovarian, breast, colon or endometrial/uterine cancer may mean you have inherited an increased risk of developing ovarian cancer.

Generally, the more relatives from the same side of the family who have had these related cancers, the greater your risk of having a hereditary cancer. However, it is still possible to inherit a gene variant without having a family history of these cancers.

Variants in the BRCA1 or BRCA2 gene are responsible for most cases of hereditary ovarian cancer (up to 20% of all ovarian cancers). These genes are named for their connection to breast cancer (BReast CAncer genes 1 and 2) but can also be associated with other cancers, including cancer of the ovary, fallopian tube, peritoneum, prostate, pancreas, and breast cancer in men.

The BRCA1 and BRCA2 genes normally help to prevent cancer, but when someone inherits a variant that stops either gene from working, they are less protected against cancer. Anyone with ovaries has about a 2% risk of ovarian cancer. However, people who inherit a faulty BRCA1 gene have about a 44% risk of developing ovarian cancer, and people who inherit a faulty BRCA2 gene have approximately an 18% risk of developing ovarian cancer in their lifetime.

Many people who have a faulty BRCA1 or BRCA2 gene do not have a known family history of ovarian or breast cancer. This can happen for many reasons:

• Not everyone who carries a gene variant will get cancer.  Other family members may have inherited a gene variant that increases their risk, but not had cancer.
• It may be difficult to see the pattern of cancer in a family. This can happen if a family is small, someone is adopted, or there are few females in the family.
• Although less common, other genes can also increase the risk of developing ovarian cancer. Someone who inherits a variant in one of these genes has a higher risk but doesn’t mean that they will develop ovarian cancer. Some other genes that increase the risk of ovarian cancer include:
• BRIP1 gene variants cause about a 6% chance of developing ovarian cancer.

• RAD51C and RAD51D gene variants causes about a 10% chance of developing ovarian cancer, as well as an increased risk of breast cancer.

• PALB2 gene variants cause about a 5% chance of developing ovarian cancer, and an increased risk of breast and pancreatic cancer.

• The mismatch-repair genes MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC)).  Variants in these genes cause up to a 15% risk of ovarian cancer (depending on the gene), and an increased risk of bowel, uterine, and other cancers.

Ongoing research may uncover new genetic links to ovarian cancer that we don’t yet know about.

More Information

• Watch our webinar on family history and genetic testing
• Cancer Council Australia has a section on family cancers with many useful resources and links.
• Visit www.genetics.edu.au