The Genes Between Us: What genetic testing can and can’t tell you with Dr Hilda High

24 Aug 2021

Most cancers occur by chance, although we know that all cancers are genetic in nature as they are caused by mistakes that build up in our DNA over time. Sometimes however a gene with a fault, or mutation, is identified as causing an increased risk of cancer in a family.  

Pink Hope with the support of AstraZeneca Australia, invited Genetic Oncologist, Dr Hilda High to explain what a hereditary cancer syndrome is, when and why genetic testing is carried and what that testing can’t tell us.  

You can view the recording of Dr High’s presentation and follow up Q&A session at this EduEvening, here. 

An easy analogy to understand cells and cancer 

Normal Cells = “Adults”, they follow the rules and understand right from wrong so function as they are designed to. 

Pre-Cancer Cells = “Adolescents” or “teenagers”, these cells like to act out by not following all of the rules, they make a few mistakes and collect a few changes to their appearance along the way but not all become ‘bad’. Changes in these cells are not passed on through inheritance in the same way a tattoo or piercing isn’t passed onto your children.  These are called a somatic mutation. 

Cancer Cells = “Delinquents”, they don’t follow the rules, they collect a lot of mistakes and become damaged as a result. The Immune System is like the “police force” and although it can hunt down and remove some of these cells, it’s not perfect. 

The healthier your cells are, the better chance your body has of fixing any mistakes that your cells make at a pre-cancer stage. This is where a healthy lifestyle becomes important as it reduces your cancer risk. A healthy lifestyle includes a diet high in fruit and vegetables and low in processed foods20 minutes of moderate exercise each day, maintaining healthy body weight, not smoking and limiting alcohol intake, this lifestyle will provide you with a 30% reduction in cancer risk.  

Hereditary Cancer Syndromes 

An inherited cancer risk is the result of a mistake in a cell that is present right from when you are conceived, as a single cell.  These are commonly genes that are growth genes (oncogene) or spell checker genes (tumour suppressors).  A mistake in a growth gene will result in cancer at a young age, a mistake in a spell checker gene comes with a backup copy from your other parent, this is where BRCA gene’s fall.  

What this means is that if you inherit a BRCA gene from one parent, your backup copy from your other parentif it is not also a BRCA gene, will protect you. However, if this backup copy becomes damaged as you age your protection is reduced and your cancer risk becomes higher. 

If you carry a BRCA gene mutation, each child that you conceive has a 50/50 chance of receiving a damaged, or mutated, gene. If you are the child of a BRCA carrier but you are tested as uninformative (no mutation found) for the genethis means that you will not pass the gene mutation onto your own children. 

Genetic Testing for Damaged Genes 

When testing for genetic mutations, it is the gene code that is looked at and identifying where the code within the gene has changed will identify if the change matters or not.  

Testing is carried out on DNA in your white cells, these are collected from your blood or saliva. Discovering where the mistake lies within the gene code also means that there are techniques that can prevent the gene from being passed onto the next generation, such as pre-implantation genetic diagnosis during IVF. During this process eggs are fertilised, at day 3 or 5, the embryos are tested and only embryos that don’t carry the mutation will be used. 

Reducing your risk if you carry a gene mutation 

To reduce the risk of developing a breast cancer a preventative mastectomy reduces the risk to a <2% lifetime chance of a new cancer, alternatively, a woman can choose to undergo annual screening with an MRI and mammogram to monitor for early detection. Hormone therapy may also be offered to a woman over 35 years of age who chooses annual screening, such as a 5-year course of Tamoxifen. This can reduce the risk of cancer by 30% but there are side effects to be considered and it is not possible to use hormonal forms of birth control. 

For men there is no screening required however they are required to monitor for any changes in the nipple or for any lumps or skin changes. 

To reduce the risk of developing a prostate cancer, PSA testing is carried out from the age of 40 with ongoing high-risk screening. This is with the view to catch any changes early and ensure a better prognosis and outcome 

For reducing the risk of ovarian cancer a woman may undergo risk reducing surgery such as a salpingo-oophorectomy (RRSO) which removes the ovaries and fallopian tubes at the age of 40 for BRCA1 carriers or around the age of 45 for BRCA2 carriers. 

Unfortunately, there is currently no screening available to detect ovarian cancer at an early stage, ultrasound or a +/- serum Ca125 identification does not affect patient outcomes such as survival and is also associated with a high false positive rate. This is due to the cancer starting and spreading within the lining of the fallopian tube making it incredibly hard to detect. 

What if you develop a breast cancer? 

ASCO guidelines outline that it is clearly the women’s choice with regards to surgery, some may choose to have breast conservation surgery (lumpectomy) only, others may choose to have a bilateral mastectomy, with or without reconstruction, to reduce the risk of any future cancers developing. Radiotherapy treatment is safe unless there is a specific genetic mutation, TP53, and chemotherapy treatment is the same for all women being treated for breast cancer. 

However, if the cancer has metastasised there are other targeted treatments that may be considered such as PARP inhibitors and platinum containing chemotherapy. 

What about other genes? 

There are thought to be around 400 breast cancer risk genes, the common ones are tested frequently such as the rare but with high risk genes we are familiar with, BRCA1, BRCA2, TP53, PTEN, CDH1 and STK11. And the rare but with moderate risk genes such as PALB2, BRIP1, ATM, CHEK2 and RAD51D. 

What do you need to consider before having a genetic test? 

The test result will confirm if there is a genetic mutation, but it cannot predict whether a cancer will occur and it cannot predict the age of onset or the type of cancer.  There are implications for other family members to be considered, but these are generally good implications, such as giving them the opportunity to also get tested and make decisions about their preventative health 

The result may also affect the ability to obtain some types of insurance and may reveal any non-maternity or non-paternity factors. 

In Australia, there is a moratorium in place, until June 2024, to ensure testing results do not impact medical or travel insurance however the result may affect a new or changed life or disability policy, although this often results in a premium deduction. 

Who can have a genetic test? 

Current eviQ guidelines and risk calculators require a 10% ‘pretest’ likelihood to be eligible for a publicly funded test, a breast or ovarian cancer diagnosis and a 10% likelihood of a mutation for a Medicare-funded test or a pathogenic mutation identified in a blood relative may also be funded by Medicare. 

It is recommended that any person in the family most likely to have a mutation is tested however children at risk of any adult-onset conditions are not tested until they are over the age of 18. 

What are the triggers for genetic testing? 

    • A breast cancer diagnosis under the age of 40 years. 
    • A triple-negative (ER, PR + HER2 negative) breast cancer. 
    • Bilateral breast cancer diagnosed under the age of 50 years. 
    • A lobular breast cancer diagnosis under the age of 40 years, especially if there is also a family history of gastric cancer. 
    • A male breast cancer. 
    • An ovarian cancer diagnosis at any age. 
    • Jewish heritage. 

It’s important to note, if you do not fit the ‘criteria’ for government-funded genetic testing, it is entirely possible to self-fund the test through a private genetic counsellor, like Dr High 

What to expect at the first appointment? 
First steps will involve the completion of a family history questionnaire, looking at two previous generations and will include both maternal and paternal sides of the family. 

It is important to speak to your family doctor or your health team if you wish to undergo genetic testing however you can utilise our online Know Your Risk Tool here and you can also access our Ask A Genetic Counsellor service here