Hereditary cancers and genetic testing

What is a hereditary cancer?

Hereditary cancer, also known as familial cancer, is cancer that occurs as a result of a heritable genetic change (variant or mutation), or genetic predisposition, which is usually inherited by an individual from a parent. Unlike most cancers which are common and tend to occur later in life as a result of environmental/secondary factors; hereditary cancers are rare and tend to present at a younger age and can affect multiple blood relatives across generations.  generations. 

How is hereditary cancer diagnosed?

Usually by clinical suspicion to start with, followed by genetic testing. The following features should raise a clinical suspicion: If you are diagnosed with certain cancers at a younger age than usual, if you have an unusual tumour pathology, or if you have had multiple primary cancers, and/or if there is a family history of related cancers (such as a family history of breast and ovarian cancers; or a family history of bowel and uterine cancers). If there is any/some of these features, your oncologist will refer you to a Familial Cancer Clinic for a further risk assessment. The assessment will take into account your personal cancer and hormonal history as well as family history to determine the likelihood of a hereditary/familial cancer predisposition is in your family. If there is a reasonable chance, genetic testing will be offered as an option and organised if you decide to proceed, usually through a blood sample.

How is genetic testing done and what are the possible results?

Genetic testing should only be done following genetic counselling regarding the pros and cons of testing as well as the potential implications of the testing results to the wider family. Testing would usually be considered in an affected family member first, who has a history of relevant cancer/s, to increase the chance of finding an answer. There are 3 possible results from this initial diagnostic testing:

1. If a causative variant can be identified in this relative, it would confirm a hereditary cancer diagnosis and further open up the option of predictive testing to the wider family to see if others may have also inherited the genetic predisposition to inform their risk management.
2. If no causative variant can be identified in this first relative, this does not exclude an underlying genetic predisposition, due to limitations of genetic testing. In this scenario, their close relatives may remain at an increased risk requiring ongoing cancer surveillance.
3. Testing may also reveal an uncertain result, showing a variant of uncertain significance (VUS), which cannot be used for predictive testing or other risk management purposes until more evidence becomes available with time for it to be re-classified to a causative variant.

What is the purpose of diagnosing hereditary cancer?

Making a diagnosis of a hereditary cancer syndrome would guide ongoing management of an individual and risk management of their relatives. For example, in a young woman who has just been found to have breast cancer, if she also has a positive gene variant and/or a strong family history, the option of double mastectomy may be considered instead of breast conserving surgery, as she is at risk of developing a second breast cancer in the future. In addition, there may be an increased risk of other cancers associated with the gene variant, such as ovarian cancer, for which risk-reducing preventive surgery would be considered in this individual. Knowing what the causative gene variant is in the family would also allow predictive genetic testing of the biological relatives to guide their screening and risk management. Those relatives who are tested positive for the family variant (those who receive a positive predictive test result) are at an increased risk of developing certain cancers, for which effective screening and risk management options may be available. Those who test negative for the family variant (those who receive a negative predictive test result) would not be at a heightened genetic risk and therefore would usually be spared of intensified cancer screening, but they would still be at population risk for cancer and thence population cancer screening still applies.

Another purpose of genetic testing is that, for those who are found to have a causative gene variant, reproductive options would be possible to reduce the chance of them passing down the genetic predisposition to their offspring. One option is preimplantation genetic testing (PGT) which involves testing embryos conceived through IVF and transferring unaffected embryos for the pregnancy to continue.

Do I need to pay for genetic testing and how expensive are they?

In the past, there is very limited Medicare cover for genetic testing. However, in more recent years, there is an increasing number of Medicare rebate item numbers made available by the Australian Government. When you are assessed at a Familial Cancer Clinic, they will also assess your eligibility for Medicare-funded genetic testing. There may also be other publicly-funded options, as well as patient-pay option. There is no private health insurance cover for any genetic testing. For patient-pay testing, the cost of testing ranges from a couple of hundred dollars to approximately $1500, depending on the type and scope of testing.

I have been told that I am gene-positive for a hereditary cancer condition, what’s next? 

This result only shows that you have the genetic predisposition, and importantly, it does not mean that you will go on to develop cancer. We also cannot predict the type of cancer, or the age of onset of cancer they will develop. Your doctor would usually refer you to a Familial Cancer Clinic to discuss your risk management options and implications to your family. Although we cannot change the gene variant, research has shown that environmental factors can influence the genetic predisposition to a degree. It is therefore important that you keep a positive attitude and live a healthy lifestyle, in conjunction with the screening and risk management program that has been recommended to you.

Whose responsibility is it to inform my relatives that I have a hereditary cancer condition?

It is usually your responsibility to let your blood relatives know, especially if you are the first one to be tested in the family. Due to the Australian privacy laws, the doctors/genetics professionals are not able to contact your relatives directly. However, the doctors can help you do so, by providing an anonymous family letter with information about your genetic condition, for you to pass on to your relatives. The family letter will encourage relatives to speak to their doctor/GP about getting referred to their local Familial Cancer Clinic to discuss their personal risk and testing options. Only under exceptional circumstances when for any reason a person chooses not to disclose a positive genetic result to their close relatives (siblings, children, parents) and where it is believed that by releasing such information it would lessen or prevent a serious risk to life, health, or safety of a genetic relative, your doctor may need to enact disclosure without consent based on the NSW Health Information & Privacy Commission Guideline. However, disclosure without consent rarely occurs in clinical practice, and would only occur after reasonable steps have been taken to ensure voluntary disclosure or disclosure by other means.  

I have heard that genetic testing may impact my insurance?

There are a few important clarifications to be made. First, it is risk-based insurance that is relevant in this context, such as life insurance and/or income protection. Second, this would only be relevant if you are undergoing predictive, or pre-symptomatic, testing, as this result would predict whether you are at an increased risk for certain cancers/illnesses. Third, there is currently an indefinite Moratorium in place initiated by the Financial Services Council and encoded into Life Code since July 2023, which means that genetic testing result should not impact your ability taking out life insurance to certain limits. More information can be found here. Fourth, any potential impact does not apply to existing life insurance policies. You would usually still have to disclose any family history at the time of taking out the policy.

I have heard that hereditary cancer is more common in certain ancestral background?

Having a certain ethnic background can increase a person’s chance of having certain hereditary cancer or other genetic conditions, due to what we called ‘founder mutations’. For example, BRCA1/2-related breast/ovarian cancer predisposition syndrome is more common among people with Jewish ancestry than those without Jewish ancestry. Genetic testing may be available at free of charge for those with Jewish ancestry. More information is available here.

Authored by A/Prof Kathy Wu (MBBS, MMed, FRACP), Clinical Geneticist (HGSA), Head of SVCG, Senior Staff Specialist, General & Cancer Geneticist. 

If you wish to know more about adult preventive genomics and/or genetic cardiac diseases, please contact A/Prof Kathy Wu.