Breast and OvarianGene

Ovarian cancer is the sixth most common cancer in women. In the general population, women have a 1.5% risk of ovarian cancer, with 75% being diagnosed after the age of 55. Most ovarian cancer occurs by chance, however up to 20% is hereditary and in some families, it may be possible to find the genetic change (pathogenic variant) which is responsible for the cancer. This allows appropriate cancer screening and risk- reducing options.

Genes are the body’s instructions and determine how the body develops and is maintained. Some genes prevent cancer developing: if there is a pathogenic variant in one of these cancer genes, then the gene doesn’t work correctly and causes an increased risk of cancer.  Pathogenic variants in several hundred genes can cause an increased risk to specific types of cancer. We also know that there must be other genes which are also associated with cancer that have not been identified yet.

Any individual with high grade serous ovarian cancer is eligible for genetic testing.

In addition families with hereditary ovarian cancer generally show one or more of the following clues:

• Breast cancer diagnosed before the age of 45/bilateral breast cancer/male breast cancer
• Jewish ancestry and a history of breast/ ovarian/prostate cancer
• Bowel/womb cancer diagnosed at a young age (before the age of 50)

The following genes have been shown to be associated with ovarian cancer and are tested as part of OvarianGene:

• ATM¹
• BARD1
• BRCA1
• BRCA2
• BRIP1
• CHEK2
• EPCAM
• MLH1
• MSH2
• MSH6
• PALB2
• PTEN
• RAD51C
• RAD51D
• STK11
• TP53    

Genes come in pairs; we get one copy from our mother and one copy from our father. At present most cancer syndromes are inherited in a dominant pattern. This means that if someone has a pathogenic variant in one copy of a gene then there is a 50% chance that they will pass this onto their children. The risk of ovarian cancer can be inherited from either side of the family.

The diagram below illustrates this:

Genetic testing can help determine the best chemotherapies as well as to determine the risk of cancer within a family and guide appropriate cancer screening. Depending on the specific genetic risk different screening tests can be arranged and risk- reducing strategies can be considered.

There are three possible results:

1. A pathogenic variant is found in one of the genes which is known to increase the risk of ovarian cancer. Specific chemotherapy may be recommended if an individual has been diagnosed with cancer. Increased screening and/or risk-reducing techniques will be recommended.
2. A genetic variant of uncertain significance is found, but whether this is the definite cause of cancer is unknown. Screening will be recommended based on the family history.
3. No variant is found. It is possible that there may be an undetectable variant or a variant in a different gene. Cancer screening/risk reducing techniques may still be beneficial.

If you have a pathogenic variant this explains why you have developed ovarian cancer and means that you may benefit from specific treatments as well as possibly being at increased risk of other cancers. Your exact risks will depend on which gene pathogenic variant has been found. Extra screening and/or risk- reducing strategies will be discussed. It will also be possible to offer predictive testing to other people in your family to see if they also have the pathogenic variant.

It is helpful for women to be aware of the signs of ovarian cancer which are:

• Increased abdominal size/significant bloating that doesn’t come and go
• Difficulty eating/feeling very full after a small meal
• Abdominal/pelvic pain
• Needing to pass urine more urgently or more frequently. 

Most of the time people with these signs will not have cancer but it is always important to get them checked out.

Diabetes, endometriosis, and ovarian cysts may increase the risk of ovarian cancer. Exposure to asbestos also increases the risk of ovarian cancer. Childbirth, pregnancy and breast feeding lower the risk of ovarian cancer. Tubal ligation (female sterilisation) lowers the risk of ovarian cancer by 35%. In addition, oral contraceptives lower the risk of ovarian cancer by up to 50% when taken for 5 or more years.