Roanoke Times
Copyright (c) 1995, Landmark Communications, Inc.
DATE: SUNDAY, July 9, 1995 TAG: 9507100106
SECTION: NATIONAL/INTERNATIONAL PAGE: A-1 EDITION: METRO
SOURCE: PAUL RAEBURN ASSOCIATED PRESS
DATELINE: LENGTH: Long
Janet didn't need a doctor to tell her something was wrong.
For more than a decade, she had watched as breast cancer stalked her family. Her mother was diagnosed in 1978, at the age of 47. Her aunt was struck a year later. The aunt's 29-year-old daughter was next, then another daughter, then one of Janet's sisters.
The two cousins and the sister died, and in 1992, the shadow fell on Janet. She, too, had breast cancer. She was 40.
By then, Janet's sister Susan - four years younger and free of any sign of disease - could not stand waiting for what she viewed as the inevitable. She scheduled surgery to have both her healthy breasts removed.
Janet and Susan - who used assumed names to protect their privacy - told their story last fall to several hundred geneticists and researchers gathered in Montreal for the annual meeting of the American Society of Human Genetics.
As Janet began, the audience fell silent. The sorrow in her voice filled the cavernous hall, where doctors and researchers were beginning to grapple with a problem unlike any they had faced before.
Last year, the mystery behind the shadow that fell on the women of Janet's family was solved. Researchers identified the gene causing the breast cancer in families like hers.
But the discovery did little to lift the shadow. Instead, it brought with it a fearsome power. For the first time, doctors could predict, decades in advance, which members of those families would get cancer and which would not.
Within weeks of the discovery, Susan became one of the first women to undergo testing. Only days before the scheduled surgery to remove her breasts, doctors notified her of the results: She did not carry the breast cancer mutation.
That meant her risk of developing breast cancer was normal - not astronomical, as it would be if she carried the gene. She canceled the surgery.
``I couldn't believe it,'' Susan said. ``It was the first reason we had for hope.''
For many others, however, including other women in Janet's and Susan's family, doctors have only bad news. Many of those women are carrying ``genetic markers'' indicating they have the mutation. And doctors can do nothing to help them.
Some day, it may be possible to pluck out harmful genetic mutations, to ``cure'' bad genes. In the meantime, doctors who have identified patients at risk can only watch helplessly as their fates unfold.
``There's that quote from Sophocles - `It is but sorrow to be wise, when wisdom profits nothing,''' said Dr. Francis Collins, the director of genetics research at the National Institutes of Health.
Collins directs the National Center for Human Genome Research, an ambitious effort to identify all the estimated 100,000 genes in humans - including an unknown number of cancer genes.
Last year, researchers discovered genes that make it possible to identify the individuals at risk in families ravaged by colon cancer. More such genes are sure to follow, Collins said.
``These genes for cancer are getting cloned willy-nilly. Testing would have potential benefits if we knew what to recommend. But we don't.''
A few years ago, doctors found the gene for Huntington's disease, a crippling and ultimately fatal nerve disorder. They are close to finding a genetic indicator of Alzheimer's disease.
Collins is among many geneticists who see a crisis building. Pressure to make testing available is coming not only from patients like Janet and Susan, but also from biotechnology companies, which stand to make a fortune selling test kits.
This new ability to predict cancer raises a host of vexing scientific and ethical questions. How should the tests be interpreted outside the research lab? Should testing be offered to anyone? What kind of psychological support should be provided?
Cancer testing also is likely to have a disastrous impact on patients' health insurance. Insurance companies may drop coverage for people carrying cancer genes. And as the ability to test for such genes grows, the pool of people excluded from coverage could grow.
``We are all carrying around pre-existing conditions, and we're learning more about how to find them,'' Collins said. ``Pretty soon, we're all going to be uninsurable.''
A further problem is that the government hasn't decided what it should do to assure the accuracy of the new gene tests and ensure they aren't misused.
The Food and Drug Administration has the authority to regulate genetic tests, but has not exercised it so far. Companies promoting the tests have not been submitting them to the FDA for approval, the National Academy of Sciences warned in a 1993 report.
The emotional consequences of testing can be so overwhelming that the tests must be nearly 100 percent accurate, the academy said. At present, they aren't.
Mary-Claire King, a geneticist at the University of California, Berkeley, did the ground-breaking work leading to the discovery of the breast cancer gene. Breast cancer runs in King's family, as it does it Janet's and Susan's.
Few people understand the significance of the test and its implications better than King. And she has decided not to take it.
``I have not screened myself. I have not screened my daughter,'' she said. ``It is premature now. The information is of no use.''
The genetic link to breast cancer in her family is weaker than in Janet and Susan's family; in King's family, the tests might not provide conclusive information on risks.
Many other families are in similar circumstances. Few families are hit as hard as Janet and Susan's, so King pleaded with women in those families to wait before seeking testing. ``Give us time to sort out the biology,'' she said.
When the biology is sorted out over the next few years, testing may become routine. But that in turn will create another problem. Genetic testing does not produce yes or no answers. The results are expressed in terms of probabilities.
In Janet and Susan's family, the probability for any individual woman is either very high or very low. But what happens when a woman has a slightly elevated probability of breast cancer, or double the usual risk? What if a young man is told he is at high risk of getting Alzheimer's in his 60s?
There will be an urgent need for genetic counselors, professionals who can interpret test results and provide guidance. Collins imagined what might happen in the absence of such counseling:
``A patient comes in and says `I lost my keys last week, and I can't remember this person's name. Am I getting Alzheimer's?'
``And the physician says, `Let's do this test.' And he says, `Yeah, you've got it. We better test your kids.'
``And some of them have it...
``And one of them goes out and blows his brains out.''
The number of Americans at risk of breast cancer, colon cancer and Alzheimer's disease reaches the tens of millions. But there are now only 1,200 genetic counselors in the United States, and Collins said the few training programs are short of funds and unable to expand.
That inevitably leaves doctors and nurses to fill the gap, even though many of them may have little genetic training.
``We have to move very swiftly if we're going to prepare physicians and nurses for this,'' Collins said.
Even the limited use of the tests thus far has revealed surprises in the way patients react. When Susan learned she was free of the genetic marker for breast cancer, her worries should have been over. Yet the good news proved to be almost as difficult to handle as bad news would have been.
First, she felt anger - ``for the hell my sisters had been through.'' Then a pervasive guilt seeped in, and remains.
``I keep thinking, `Why did they inherit it and I didn't? They're good people.' I'm the only one out of five children that didn't inherit the marker. The next day I remember not being able to get out of bed.''
Janet concluded her remarks to the geneticists with a word of thanks - and a hope.
``We as a family feel tremendously grateful that something has been happening for us,'' she said.
``I wish you all a lot of luck in figuring this out.''
by CNB