Sunday September 14, 2008
Testing, testing genes
By Dr TEO SOO HWANG
This is the third article in a series of four articles by the Cancer Research Initiatives Foundation (CARIF) that explores how genes are linked to diseases, the relationship between genes and cancer, and what is genetic testing and counselling. This week, we explore whether direct-to-consumer SNP-based genetic testing adds anything to our ability to prevent disease.
THIS may happen soon: Scenario 1 – Samy is 50 years old, overweight and does not exercise regularly. Samy’s father had a heart attack in his 50s and Samy is worried that he will have a heart attack soon. Samy’s doctor tells him that he needs to lose weight, stop smoking and exercise regularly, and this would reduce his chances of getting heart disease.
But Samy likes his char-koay-teow, roti chanai and five meals a day too much, has not gone on a diet, has not given up smoking and does not do any exercise. A year later, he is afraid to go back to the doctor.
At a shopping centre, a pretty sales executive tells him that for a mere US$1,000 (RM3,300), he can do a genetic test which would tell him whether he has an inherited risk to heart disease, cancer and diabetes. Samy is ecstatic because the executive tells him that perhaps only 20% of the population will be classified as high risk, and Samy reckons his chances are good and goes ahead with the test.
There is a lack of public awareness about genes and the risk of disease, and the technology of genetic testing. The test (a whole genome analysis at multiple single nucleotide polymorphisms or SNPs – pronounced “snips” – ie a test to detect small genetic changes or variations that can occur within a person’s DNA) tells him that he is not at high risk relative to the rest of the population.
Samy interprets this to mean that he can go on with his high-fat food, cigarettes and no exercise lifestyle. Six months later, Samy has a heart attack and dies before his 51st birthday.
Samy’s wife and children are devastated, but the company’s report says that the test was “not a clinical service to be used as the basis for making medical decisions”. Who is responsible for Samy’s death?
Scenario 2: Nur is now 31 but she was just a teenager when her mother and aunt died of breast cancer. Another aunt has just developed breast cancer and Nur is worried that she will be next. Her doctor tells her that because of her family history, she is at high risk of developing breast cancer and advises her to attend regular mammograms, although mammograms are not very sensitive for women under the age of 40.
At the shopping centre, a helpful “health screening” executive offers her a genetic test for a mere US$1,000 (RM3,300). Nur goes ahead and is ecstatic because the test shows that she is not at high risk to cancer. Nur decides not to undergo any further mammograms.
Three years later, Nur notices a lump in her breast and is diagnosed with Stage III breast cancer. Nur is devastated, because the cancer could have been detected earlier if she had attended regular mammograms and she may not have needed the full mastectomy that she now needs because of the late diagnosis. Who is responsible for Nur’s breast cancer?
Since 2007, there have been a large number of genetic studies showing that some genetic changes are linked to common diseases, including heart disease, cancer and diabetes. For the first time, such studies have identified some genetic changes, which were not previously suspected to be related to disease, to be associated with disease.
This is hugely exciting because for the first time, scientists have a genetic location to look for the genes that are linked to these diseases. In other words, instead of looking at three billion bases (alphabets) of the human genome, scientists can focus in on the most likely two million bases for those genes.
But even before these genes have been identified, some companies have already started offering direct-to-consumer genetic tests for common diseases. The claim is that from just a spoonful of blood, they may be able to tell whether an individual is at risk of heart disease, cancer, diabetes and a host of other diseases.
There remain major problems in letting the “genome genie” out of the bottle. First, while some genetic tests such as tests for the breast cancer genes BRCA1 and BRCA2, and up to 1,100 other genetic tests are well-validated, the more recent “personal genome tests” remain largely unvalidated.
The contrast is clear: whereas the genetic tests that use a technique called DNA sequencing examines every single base (alphabet) of the disease-causing gene, these newer genetic tests “scan” many genes, without examining every base. By analogy, whereas some genetic tests involve reading an instruction book in detail, other genetic tests only read one or two words from each chapter.
In the example above, because the SNP test only scanned Nur’s genome without reading every single alphabet of the most relevant gene, it missed the single alphabet change in the BRCA1 gene, which meant that Nur had an 80% chance of developing cancer.
In addition, whereas “conventional” genetic tests examine genes that significantly increase risk (for example, increase the likelihood of getting cancer from 2% in a normal individual to up to 80% in a carrier), the SNP test examines genetic changes that cause only a modest increase in risk (for example, increase the likelihood of getting cancer from 2% in a normal individual to 4% in a carrier).
If you were told that you had an 80% chance of developing cancer, you may consider prevention very seriously. Would you take it so seriously if it was only 4%?
We also do not yet know how the information will be used in the clinic: if a patient is found to be at risk for a disease, what can be done about it? We have many assumptions about potential benefits, but few answers.
The added danger is that whereas there are few carriers with high risk genes in the population (less than 1%), there may be many carriers of low risk genes in the population (up to 20%). The lack of public awareness about genes and the risk of disease, and the technology of genetic testing, would mean that doctors may face a situation of managing many individuals whose test results show a high risk but who, in reality, may very well be free of disease.
Ultimately, most of the diseases listed by SNP testing are so-called complex diseases (diseases thought to be caused by multiple gene variants and modified by our lifestyles and diet). We still do not understand enough about how these different genes interact with each other or with the lifestyle, environmental and dietary factors. Thus, we cannot use the information (yet!) to distinguish the people who will develop the disease from those that will not.
It may be argued that armed with knowledge that his father had a heart attack and that he is at risk because of his obesity and lack of exercise, Samy should have begun an exercise routine and controlled his diet – regimes which we KNOW will decrease his risk for heart disease and diabetes.
Also, Nur and other women who have a family history of breast and ovarian cancer should have seen a genetic counsellor and clinical geneticist who are experts on genetics so that she can understand the facts about her situation.
In fact, all women, regardless of their family history, their lifestyle, their diets and so on have a risk of developing breast cancer – the important message is that all women should be breast aware (ie aware of any changes in their breast) and should have mammograms once a year if they are more than 40 years old.
It is clear that genetics will revolutionise the way we approach medicine as it will enable us to identify individuals who are at risk to disease, and hopefully understand how changes in lifestyle, environment and diet may be able to reduce that risk.
However, there are at present few good genetic studies in Asians. Despite the wealth of information now available, the promised benefits of personalised medicine will at best, be only partially realised, because we know so little about genes in Asians.
Genetic studies rely, after all, on the good will of thousands of subjects who agree to have their DNA studied, from just one spoonful of blood.
Will you take part in Malaysian research studies to understand genetics in our population?
The fourth and final article in this series will explore the importance of an individual’s family history in assessing the need for genetic testing, and the role of experts (genetic counsellors and clinical geneticists) in providing information and services in the genetic testing process.
Dr Teo Soo Hwang is the Chief Executive of Cancer Research Initiatives Foundation (CARIF). CARIF is a Malaysian independent cancer research organisation whose mission is to conduct fundamental and pioneering research on cancers prevalent in Malaysia, with potentially far-reaching implications for prevention, diagnosis, treatment and therapy. CARIF is focused on cancer research in Malaysia especially in the areas of breast cancer, oral and nasopharyngeal cancer and developing new cancer therapies from our country’s biodiversity. For further information, e-mail starhealth@thestar.com.my. The views expressed are those of the writer and readers are advised to always consult expert advice before undertaking any changes to their lifestyles. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this column. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.
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