Doc Talk

Human destiny is in genetic make-up but we are not powerless to act

Patients often ask me: "Doc, why did I get cancer?"

The usual reply I give is: "Your cancer is the result of bad genes and your environment".

A poor lifestyle, combined with "bad luck", leads to multiple random genetic mutations that cause cancer.

But the recent advent of highly powerful gene sequencing applied to cancer informs us that about 20 per cent of ovarian cancer is the result of "single gene mutations" inherited directly from one parent, with the potential to be passed down through the generations.

The most well-known of these are BRCA1 and BRCA2.

Whereas the lifetime risk of ovarian cancer is 1.3 per cent for the normal (background) Singaporean population, carriers of the BRCA genes would have a lifetime risk of developing ovarian cancer of up to 40 per cent and a lifetime risk of breast cancer of 65 per cent.

Ovarian cancer management today is changing rapidly, in parallel with new knowledge of the genetic basis of the disease.

Patients diagnosed with ovarian cancer are counselled to test for BRCA and other hereditary genetic markers. If they test positive, the rest of their "blood-kin" - sisters, brothers and children - will be called to go for similar testing.

This creates a conundrum.

While being "test negative" offers a huge sigh of relief, those who test positive for BRCA will have an extremely high risk of developing ovarian and breast cancer somewhere in their lifetimes.

They will worry. Although they may remain well for years, they would be constantly living under a sword of Damocles.

Mothers with ovarian cancer who do the test will fret for their children - whether they would ever find marriage, health insurance, happiness and normalcy - if their own test results return positive for these hereditary cancer genes.

Guilt, stigma and shame have complex behavioural response theories in Eastern and Western cultures, but the sheer anxiety created by genetic "fore- knowledge" is perhaps universal.

Human beings live in hope and a fundamental belief that we are in control of our lives and destiny.

If we avoid smoking, exercise regularly and are careful with our diets, we might avoid the worst.

But genetic determinism (and science is increasingly efficient at testing for some of these mutations) now threatens to take away this very core human belief - of control over our lives.

Novelist Somerset Maugham summarised it well when he wrote: "I act as though I were a free agent. But when an action is performed, it is clear that all the forces of the universe from all eternity conspired to cause it and nothing I could do could have prevented it. It was inevitable."

But does genetic testing really need to leave so little wiggle room?

Firstly, only half of the children of BRCA carriers will inherit the mutation. Those who do not inherit the gene will have a normal cancer risk - similar to the background population (1.3 per cent or one in 80 for ovarian cancer, and 6.8 per cent or one in 15 for breast cancer) - and all their children will likewise have "normal" risks.

Secondly, those who do inherit the mutation have a very viable recourse with preventative "risk- reducing surgery". This involves removing both breasts (with plastic surgery reconstruction), ovaries and fallopian tubes - after completion of one's family.

Although it is a difficult step, such risk-reducing surgery is extremely effective. Hollywood actress Angelina Jolie, a BRCA carrier who underwent preventative surgery in 2013 and 2015, continues to lead a normal and active life.

Thirdly, cancer patients who have a BRCA gene mutation stand to benefit from new treatments.

Olaparib, the first cancer drug that specifically targets an inherited genetic biomarker (BRCA), has recently been approved for advanced ovarian cancer. This is an oral cancer drug with minimal side effects that is effective at delaying ovarian cancer relapses.

Genetic knowledge, though burdensome, does bring benefits.

Rosalind Franklin was an astonishingly brilliant scientist who discovered the helical structure of DNA, which contributed the basis to the work of James Watson and Francis Crick, the celebrated scientists who first published the three-dimensional structure of DNA, the complex molecule that forms the basic building block of life. But she was denied the Nobel Prize because of her premature death from cancer. She was Ashkenazi Jewish and it is widely believed that she died from BRCA-associated ovarian cancer.

Fifty years later, her pioneering work has led to a vast body of knowledge and sophisticated DNA- sequencing techniques that could have spared her cancer, had they been available to her at that time.

True, human destiny is sometimes in our genetic make-up and our fates are outlined in the stars. Yet we are not powerless to act.

Even for BRCA carriers, the simple action of bearing children to complete their families early and then pursuing risk-reducing surgery can fundamentally alter the genetic predestination to cancer.

In the plays of Euripides and Sophocles, the "tragedy" occurs when the protagonist actively contributes to his fate and destiny due to some character flaw.

His destiny is only inescapable because he carries the flaw - hubris and ignorance - inside him that blinds him to the warning signs, thus guiding him inevitably towards his fate.

We should take heed not to dismiss the benefits of knowledge and to grasp the chance for intervention. And as a society, we will also need to develop better policies for healthcare, insurance and education that will allow us to adapt to the enormous growth in technology.

This will be necessary if we, as a society, are to reap the full benefits arising from the tremendous progress of science.

As former United States president Bill Clinton said at the announcement ceremony for the Human Genome Project in 2000: "It is now conceivable that our children's children will know the term "cancer" only as a constellation of stars."

•Dr Chia is senior consultant and chief of the gynaecology oncology team at the division of medical oncology at the National Cancer Centre, Singapore. For the past 10 years, he has been extremely active in clinical trial research. His passion has been to improve cancer outcomes for his patients - through research, early diagnosis and care protocols.

A version of this article appeared in the print edition of The Straits Times on September 13, 2016, with the headline 'Human destiny is in genetic make-up but we are not powerless to act'. Print Edition | Subscribe