Brace yourself, genetic testing might give you more than you bargained for

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BRCA1 and BRCA2 gene mutations prompted Angelina Jolie to have a preventative double mastectomy and surgery to remove both ovaries. Sebastian Kahnert/AAP

Drink red wine to prevent cancer. But don’t drink too much! Get some exercise. But don’t overdo it. Give up, it’s all genetic anyway – think of Angelina Jolie!

We are constantly bombarded with conflicting information about our risk of developing cancer. It is difficult to know who to believe, let alone how to respond.

What if you could take a simple test that would reveal your individual risk of developing not only a range of cancers, but hundreds of other diseases? Imagine if it could also tell you which drugs would be most effective for you, if you did develop cancer or other diseases.

The rapidly reducing cost of DNA sequencing has made this one-time fantastical idea an emerging reality. Only 10 years ago it cost about US$10 million to sequence a human genome, so there was little prospect that individuals would, or could, seek out their own unique genetic maps to find out more about their ancestry or their inherited health risks.

Recent advances in genetics mean genetic sequencing is more affordable (US$1,000 to US$3,000) and already guiding treatment across a range of illnesses from cancer to degenerative brain diseases.

New unregulated direct-to-consumer businesses are emerging, making it possible for anyone to order their individual genetic profile by posting off a saliva sample taken at home. But do you really know what you are signing up for?

The age of personalised medicine

Personalised medicine means using a patient’s genome to both predict their likelihood of developing certain diseases, and to guide which treatments are most likely to be effective in a particular individual. It’s also called customised medicine, precision medicine, individualised medicine, bespoke medicine and targeted medicine.

Our genes hold our hereditary information. Every cell in the human body is made up of about 20,000 genes that are passed down from parents to child. Genes contain information that instructs the growth, development and function of the human body. Some genes control simple characteristics such as hair colour and height, others influence complex characteristics such as intelligence. Some genes control how other genes work, telling them when to switch on and off.

Some genes control simple characteristics such as hair colour and height, others influence more complex characteristics like intelligence. from www.shutterstock.com

We all have alterations, or mutations, in our DNA. Mutations can be passed down from parents to children, or can occur spontaneously, especially as we age. Some are harmless and may determine, for example, whether our ear wax is wet or dry.

However, a mutation in an important gene that prevents it from working properly, or a gene that is missing altogether, can have serious consequences. Early genetic testing focused on debilitating inherited diseases, such as cystic fibrosis and Huntington’s disease, that are caused by mutations in single genes. Tests looked only for a known mutation in a specific gene to confirm or rule out the associated condition.

As testing has become more sophisticated, we have been able to extend this approach to more complex conditions such as cancer. Mutations in two genes called BRCA1 and BRCA2 are associated with an increased risk of developing breast and ovarian cancer, and can be inherited within families.

BRCA1 and BRCA2 normally help clean up mistakes in our DNA that our cells can make when they divide, a process called DNA repair. When either of these genes is altered or mutated, this protective function is disabled, leading to uncontrolled replication of cells with mistakes. This can lead to cancer.

The good news is that we can test for these mutations, and patients can then use the results of this test to assess their risk of developing cancer, and make informed choices. This is the same hereditary genetic mutation that prompted Angelina Jolie to have a preventative double mastectomy two years ago, and preventative surgery to remove her ovaries this year.

The other good news is that in recent years scientists have discovered that patients with mutations in BRCA1 and BRCA2 are exquisitely sensitive to some forms of chemotherapy and a second type of drug called a PARP inhibitor. The same mutation that generates the mistakes in these cells can actually make them more responsive to this drug. Decisions about treatment can then be “personalised” to the individual.

What does the future hold?

Currently, health systems in Australia and overseas do not offer patients the option of sequencing their entire genome as a means of identifying and managing future health risks. Today genetic testing is only available in Australia for specific genes, is tightly regulated and is used only when symptoms are apparent, or a genetic risk is likely, such as a close relative developing a particular cancer or condition.

In five to 10 years’ time, however, we may be facing very different choices, including the option to look for future diseases before they actually occur.

As many cancers do not appear until middle age or later, a young healthy person might discover they have various elevated risks among the many anomalies a DNA test could throw up. Such results might not be provided by a medical professional, but by a commercial operator, and without genetic counselling to explain what they mean to the individual and their family.

Insurance companies could use genetic profiles to deny higher-risk individuals various types of insurance, or increase their premiums. from www.shutterstock.com

What might the implication be of a high-risk result? Should an individual’s relatives be informed, as their risk may also be high, or do they have a right not to know? And what about minors: will parents have the right, or even an obligation, to test babies and children for potential genetic risks, even if medical science offers no prevention or treatment options?

Are we psychologically equipped for these kinds of dilemmas and scientifically literate enough to interpret our own results?

There are currently many reasons to be cautious. First, there are potentially millions of genetic alterations. Most are still not understood. Personalised medicine cannot currently give anyone a comprehensive picture of individual risk simply because far too much remains unknown.

Second, personalised medicine can only indicate elevated risks, it cannot determine whether or not a patient will actually go on to develop a certain type of cancer. Environment and lifestyle also play a big role in our health.

Insurance companies, however, deal entirely in risk. That means genetic profiles could be used to deny higher-risk individuals various types of insurance, or increase their insurance premiums.

Third, health outcomes for some individuals may be based on the financial viability of developing drugs. Many drugs and therapies are currently used for large numbers of patients, making them financially viable for pharmaceutical companies to develop. Genetically targeted cancer drugs, suitable for much smaller groups of patients, may be extremely expensive or might not be brought onto the market at all if society is not willing or cannot afford to pay for them.

Fourth, we may be at risk of eroding our quality of life by creating a new state of “worried wellness”, waiting for disease to strike.

Finally, we may not be sufficiently savvy consumers. New commercial operators are coming onto the global market offering a range of largely unregulated services. Currently, you don’t get much more than details of your ancestry for a US$99 DNA test. But more specialised businesses are emerging that offer, for example, to “identify potential health risks that are present now or may develop in the future”.

Is this just hype, and offering unsubstantiated hope to consumers, or does this represent the first stage of patient empowerment over their own health and lifestyle choices? It will be fascinating to watch this new age of personalised medicine develop in the coming years.

The authors do not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article. They also have no relevant affiliations.