Familial genetic testing

Sarah Walters describes genetic testing for familial breast and ovarian cancer.

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Approximately 1 in 8 to 1 in 12 women is at risk of developing breast cancer. However, not all breast cancers are inherited. We may know families (our own or friends) where there are many members affected with breast or ovarian cancer. This may be caused by what we know as the familial, or inherited type. 

Only about 10% of all individuals with breast or ovarian cancer are identified as having an inherited type of cancer. Therefore, approximately 90% of all affected people have a sporadic type of cancer – that is, there is no obvious known cause. 

BRCA1 and BRCA2

Many of you may have heard about the breast and ovarian cancer genes, known as BRCA1 and BRCA2 mutations.  

This group of genes, that BRCA1 and BRCA2 belong to, are known as tumour suppressor genes; every person has two copies of BRCA1 and BRCA2. Their normal function in cells is to regulate cell division, to stop cells from dividing too many times. Similar to you putting your foot on the brake pedal when going down a hill. But when there is a mutation or change within the gene, the brake pedal doesn’t work properly. Hence an increased risk of developing breast or ovarian cancer.

BRCA1 and BRCA2 are not the only genes that can cause cancers; there are others.  

Family warning signs

There are many clues that help healthcare professionals to determine whether the predisposition to a cancer may be inherited or not. 

It is crucial to find out and report any family history of breast or ovarian cancers and other types of cancer that may be related, such as colon and prostate cancer, to your healthcare professional. 

A strong family history of cancers can indicate that there is an underlying heritable component. 

Family warning signs to look out for:

• Four or more cases of breast cancer in the family diagnosed before 60 years old.
• Three cases of breast cancer in the family diagnosed before 50 years old.
• Two cases of breast cancer and one of ovarian cancer in the same side of the family.
• Male breast cancer diagnosed. 
• You come from a high-risk ethnic group (e.g. Ashkenazi Jewish or Afrikaner background).
• You have a personal history of breast cancer diagnosed at a young age (before the age of 40 years).
• You have a diagnosis of bilateral breast cancer.
• There is a person in your family affected with both ovarian and breast cancer.

Testing of the breast and ovarian cancer genes

Your genetic counsellor/healthcare practitioner will advise you which genetic test is most appropriate for you based on the above factors. 

Targeted testing for common mutations in the BRCA1 and BRCA2 genes may be appropriate, based on your family ethnic background. This type of testing will look only at specific places in the BRCA1 and BRCA2 genes for faults.  

Alternatively, full sequencing of the genes may be a more appropriate test option. Sequencing of a gene is similar to reading a chapter in a book. The genetic scientist will read every single letter of every single word in the chapter, to ensure that there are no spelling mistakes, words that have swapped around, or pieces of the chapter missing, or anything extra that has been added by mistake. 

If differences are found, they are compared to see if they have previously been reported to be involved in predisposing someone to developing cancer. 

Inheriting a fault on one of the genes, does not necessarily mean that you will develop cancer, but it does increase the chances that you can. 

Pros and cons of familial genetic testing

These should be discussed with your healthcare practitioner or genetic counsellor. It is your choice to be tested for an inherited predisposition to cancer, especially if you have not been diagnosed (predictive testing). 

It is important to be aware that knowing that you are positive for a familial genetic fault means that other members in your family may also be at risk. 

Family members over the age of 18 years would be eligible for testing, should they so choose, so that early screening and detection may be made available to them.