Say your sister has breast cancer. Say you've heard of BRCA1 and BRCA2, the genes which are mutated in 25 percent of women younger than 45 who get this disease. Say you want to know your risk.
Say Alzheimer's runs in your family — your Dad has it. Say your older brother is in his 60s, and you're not that far away. Say you've heard of ApoE, on chromosome 19, now widely available for testing. Say you want to know your chances.
Welcome to the brave new world of genetic testing. It's a world in which testing comes before knowing, and knowing is everything. It's a world in which 26 states passed antidiscrimination and pro-privacy laws last year, while 20 bills pending in Congress would do the same. It's a world in which some Florida, North Carolina and Louisiana employers wish everyone would just forget about the time they could test for sickle cell trait. Their state legislatures had to pass laws to make sure they remembered.
Genetic screening is coming fast. What are the basics?
Genetic screening is testing plus counseling — not testing alone. Testing is not just DNA-based, but any laboratory testing that yields genetic information. Counseling is genetic counseling, preferably by a genetic counselor certified by the American Board of Genetic Counselors.
What make good criteria for screening? According to the "1994 U.S. Preventive Services Task Force Report," that question is best answered after asking three more questions:
- What is the prevalence of the disease?
- What is the accuracy of the test?
- What is the effectiveness of early detection?
Some genetic tests are well accepted and in wide use. Newborn screening, carrier testing (for example, for cystic fibrosis) and prenatal diagnosis all use genetic screening. In cancer, testing for early detection, diagnosis, prognosis and treatment all have their advocates and legitimate uses. The real interest to employers and insurers, however, is predictive testing for hereditary susceptibility to genetic disorders.
For most screening tests, the predictive value is very low — so low as to be of little or no use (retinoblastoma and Wilms' tumor are two exceptions.) But consumers want knowledge — for themselves, not for insurers' actuarial risk analysis and adjustment — no matter how many false positives a test yields.
What consumers think
Still, consumers are reluctant to share their knowledge with anyone — including their doctors. Why? Plain and simple: fear.
A study, "Genetic Discrimination: Perspective of Consumers" (Science 1996; 274:621– 624) quantified this fear. The investigators found that of 332 relatives of people with a genetic disorder, 22 percent of respondents thought they or a family member had been refused health insurance because of it. Eighteen percent had kept genetic information from an insurer, and 83 percent would not want their insurers to know if they were tested and found to be at high risk for a disorder.
Would informed consent and promises of privacy help? Maybe not. A 1997 New England Journal of Medicine report found that only 17 percent of tested patients gave informed consent to having a test that detects mutations linked to familial adenomatous polyposis — a condition that can be diagnosed without genetic testing.
But informed consent is worth a try. The three components of informed consent — adequate information, reasonable understanding and absolute volition — are familiar to many physicians. The psychological, familial and medical impacts are unpredictable in genetic testing.
Employers and fairness
If managed health care were not primarily employment-based, people would have much less to fear.
It might be more equitable to separate health benefits from employment, offer an annual stipend or credit and ask people to purchase their own health care. It might be more equitable to consider health care a right instead of a privilege, and to fund it through higher public taxes and private clinics. It might be more equitable to reduce demand for intensive testing and treatment by building people's confidence in their ability to care for themselves and to blunt the expression of unfavorable genes.
But most employers are neither interested in creating the picture of health in their work forces nor in the tenuous nature of genetic predictive diagnosis. They are interested in fitness to work, not working to become fit. They are also necessarily interested in the Americans with Disabilities Act, an antidiscrimination law with privacy protections.
When genetic screening is improved, every person will be found to be at risk for something. More linkages are discovered literally every day. The genome will be mapped within 10 years, and all of a person's 100,000 genes will have a locus.
The results of genetic screening should remain anonymous, perhaps even in cases where the safety of workers is at issue. Anonymous testing means that which is invisible to medical records. Access to genetic medical information matters more now than its use.
Can privacy exist?
If genetic information is collected, employers, insurers and pharmacy benefit managers will find a way to get it. It's hard to imagine that keeping test results in a separate folder (especially an electronic one) will really mean the difference between private and public.
In the meantime, clinicians asked about genetic screening by their patients can help by giving them good information from the National Society of Genetic Counselors (1-610-872-7608) and the National Cancer Institute (1-800-422-6237).
Cancer is where there are the most questions and fewest answers. There are 185,000 new breast cancer cases annually, but only 5 to 10 percent, at most, are linked to breast cancer genes. More than 200 mutations occur at these sites. And the penetrance of the mutation that results in breast cancer is between 65 and 80 percent — it is not 100 percent. Before testing a patient who wants to know her genetic susceptibility, most counselors advise testing one of her relatives with the disease for a genetic mutation — and, if the result is positive, then testing the patient.
While lawyers are litigating it, and regulators are regulating it, clinicians will have to answer questions about it. Make sure you:
- Distinguish between testing and screening.
- Distinguish between research and practice.
- Engage or contract with a genetic counselor.
- Insist on written, pre- and post-test informed consent.
- Know that the law is a floor for ethics. They are not the same.