March 2007
Written by Erica Brown

Tags: Health, screening.

You’re in your twenties. You just got a big promotion and you’re dating this really great person. Life is going really well. But often there’s something nagging at the back of your mind… You’re worried about a disease running in your family. Individuals are healthy until about 40 years. And then movement and walking problems appear, personality changes surface, and severe intellectual decline sets in. Is this going to be your fate? Would you want to know, or would you be better off not knowing?
You need to consider this difficult question very carefully. Because once you know what your future holds, there’s no going back. Once asked, the mirror never lies…

What is predictive testing?
Predictive testing tells an individual at risk of developing a disease if she is likely to, or definitely will, develop the condition in the future. It’s kind of like scientific crystal ball gazing.

There are two general categories of predictive tests:

• Pre-symptomatic testing predicts with certainty that the condition definitely will, or definitely will not develop. For example, predictive testing for Huntington’s disease (described above) and Familial Adenomatous Polyposis (a type of colon cancer) gives a definite yes or no answer about whether a person will develop the condition or not.
•  Susceptibility testing does not give a simple yes or no answer whether the individual will develop the condition or not. Rather, if the test reveals a faulty gene, the individual has an increased chance of developing a particular condition but other genes and environmental factors will play a role. For example, individuals who carry a faulty gene for hereditary breast cancer have an increased risk of developing breast cancer but the cancer may never develop.

Who has predictive testing currently?
Usually, it is individuals who have a family history that puts them at increased risk for a genetic condition that shows up later in life who may seek out predictive testing. Huntington’s disease, familial adenomatous polyposis and hereditary breast cancer are all examples of conditions where predictive testing has been offered for some time.

How do you know what is a good predictive test?
Knowing the health hand you’ll be dealt in the future seems like pretty heavy stuff. How can you judge the usefulness of a predictive test?

How valuable a test is depends a lot on personal perceptions of the usefulness of information gained from the test. Here are some factors to consider when deciding on the usefulness of a predictive test:

What is the nature of the condition for which testing was sought?

• How severe and devastating a condition is it? For example, knowing about the onset of a seriously debilitating condition like Huntington’s is likely to be a very burdensome weight to carry around compared to knowing you have a susceptibility to grey hair.

What are the limitations of the information gained from the test result?

• With Huntington’s disease, if you have the faulty gene, then you can be sure that you will eventually develop HD. However, the test can’t tell you at exactly what age symptoms will start or how severe the symptoms will be.
• If predictive testing for hereditary breast cancer finds that a woman carries a faulty gene, it doesn’t mean that she’ll definitely develop cancer. She may never develop the disease. Alternatively, the two genes (BRCA1 and BRCA2) currently tested for are thought to account for a maximum of 1/3 of hereditary breast cancers. (It is important to note that only 5% of breast cancer is considered hereditary, where people have inherited a mutation.) Therefore if genetic testing on BRCA1 and BRCA2 is negative, it doesn’t mean that the individual is not at increased risk for breast cancer (the individual may have an alternation in another as of yet unidentified breast cancer gene). Plus the test does not ‘catch’ all mutations so you can have a mutation in BRCA1/2 but the test may not see it.

Is a treatment for the condition available? And if so, how effective is it?

• It is often more conceivable for individuals to consider predictive testing if there are screening and surveillance measures that can prevent or slow the disease
• For example, studies have shown that for individuals at risk for familial adenomatous polyposis (FAP), where effective surgical treatment exists, 90% choose to have the predictive test. With hereditary breast cancer, screening and interventions are less effective and about 50% of individuals choose to have predictive testing. With Huntington’s disease, where no treatment exists, only 20% of individuals choose testing (1).

Possible benefits from testing
Some benefits of predictive testing may include:

• Regardless of the result, testing can end the uncertainty surrounding the chance of developing the condition
• If a faulty gene is found, it can allow time to plan for future health care, making more realistic life choices or employment decisions, and informed reproductive decisions.
• If a faulty gene is detected and screening and treatment options exist, these can be initiated to prevent or slow the onset of the condition and promote well-being.
• If an individual doesn’t carry the faulty gene, a huge burden may be lifted and a less stressful life may be led.

Possible implications from testing

Predictive genetic testing– a really different ballgame compared to regular medical diagnostic testing– raises many special issues. For example, regular diagnostic testing rarely has implications for other family members. But the fact that many family members share the same genes means that predictive genetic testing on one family member often has implications for others in the family.

Let’s look more closely at Huntington’s disease (HD) to see why this is the case. HD, an inherited brain disorder that causes symptoms like movement and walking problems, personality changes and intellectual decline, is inherited in a dominant pattern. This means that an individual who has HD has a 50% (1/2) chance of passing the altered gene to their child and a 50% (1/2) chance of passing on the normally functioning gene (it’s like flipping a coin). Say ‘Marie’ has a father who was diagnosed with HD and Marie is adamant that she does not want to know if this is also going to be her fate. Marie’s adult son ‘Tom’ wants to know if he inherited the faulty gene from his grandfather. The implication of testing Tom is that it may mean revealing Marie’s genetic status if Tom is found to have the faulty gene (remember Tom would only inherit the mutation if his mother also has it). Alternatively, if Marie had testing and was found to carry the faulty gene, Tom would suddenly find that his risk of carrying the faulty gene was increased from 25% to 50%.

Other implications of predictive testing

• Reproductive decision making: Finding out about the inevitable or about the likely onset of a genetic condition may mean facing difficult decisions about whether or not to have children, whether to have prenatal testing, or whether to start childbearing earlier than originally planned.
• Survivor Guilt: Predictive testing showing that an individual is not at risk for a genetic condition running in the family may evoke feelings of guilt that they escaped inheriting a condition that they’ve seen affect parents, grandparents or siblings. Alternatively, some individuals not at risk for the genetic condition may find themselves excluded from the family ‘club’ of members affected with the condition.
• Employment Discrimination: Knowing one has a genetic condition that will onset later in life may impact negatively on employment opportunities. While employment discrimination based on predictive testing results is not known to have occurred in Canada, we can’t rule out that this may be a problem in the future.
• Insurance Discrimination: Individuals who have had genetic testing must reveal this to life insurance companies and this may impact on an individual’s eligibility for, or cost of, getting life insurance.
• Psychological Burden: A heavy burden may come with the knowledge of a looming condition, especially one that’s untreatable. For this reason, it would be important for a person to think about how they would cope with this type of information and who they can rely on for support before having the test.

Detailed discussions all of these issues as well as the limitations of the test and possible results should take place with a geneticist, genetic counselor or other knowledgeable professional before testing takes place.

Can you change your future?
Marty McFly and Doc Brown in the Back to the Future sequel were able to glimpse the unfortunate future that lay ahead for them and make changes to prevent it from happening. Can the same be done with later onset genetic conditions? Aside from the screening and preventative measures available for some conditions (eg. Surgical treatment with FAP), there is currently no way to cure a genetic condition. Research in the area of stem cells and gene therapy may one day mean some genetic conditions are curable, but at the moment knowing about the future onset of a genetic condition doesn’t allow for treating it.

Would you choose to have a predictive test? Click here to check out an activity

References

1. Harper P. Practical Genetic Counselling. 6th edition. Arnold. 2004.
2. Nutrigenomics: Report by Nuffield Trust and Public Health Genetics Unit. Feb 2004. www.nuffieldtrust.org.uk
3. Gorman C. Does my diet fit my genes? Time. Jun 11 2006.
4. Russo G. Home health tests are ‘genetic horoscopes’. Nature. 442(3):497. 2006.