Caution urged in choosing gene tests

WASHINGTON — Everyone's genes spell out a risk for some disease, and a coming anti-discrimination law is about to give genetic testing a boost.

But discrimination is just one hurdle. The bigger quandary: Doctors don't yet know how many of the genetic tests being pushed for dozens of conditions are truly useful — and how many are misleading at best.

"Some of these tests are complete rubbish," warns Dr. Howard McLeod, a personalized medicine specialist at the University of North Carolina. "The big challenge for a consumer is figuring out which data is real or not without having to go to medical school."

President Bush is expected soon to sign into law federal protection against genetic discrimination, a bill barring employers and insurers from using test results against patients.

First to benefit will be people who put off learning if they inherited genes responsible for diseases that run in their families — breast cancer, colon cancer, Huntington's, early-age Alzheimer's — for fear of losing insurance coverage or a job.

No one knows how many people that encompasses. The National Institutes of Health estimates 30 percent of potential volunteers for gene studies cite discrimination fears in backing out. At the same time, states have adopted a patchwork of protections, and steadily growing use of two of the best-proven tests — for the BRCA1 and BRCA2 gene mutations linked to breast and ovarian cancer — suggests that lingering concern hasn't been a huge deterrent for people with strong family histories of disease.

But until now, most genetic testing has been for conditions linked to single genes gone wrong, typically rare ones.

That's changing.

Most diseases — including diabetes and the No. 1 killer, heart disease — are caused by complex interactions of multiple genes and environmental factors, such as diet, exercise and smoking. With scientists rapidly discovering gene variants for these more common conditions, genetic testing in turn is poised to boom.

Yet laboratories can market tests for those newly discovered DNA glitches before scientists prove how risky they are, or whether knowing you have one will make any difference in your health care.

Nor are lab tests subject to the same scrutiny as medical treatments. So while the pace of discoveries makes for a thrilling time, genetic testing in some ways is science's Wild West — with more than 1,200 different genetic tests available but only a fraction accepted by mainstream medical groups, McLeod said.

Just last week, government health advisers called for more oversight of genetic testing, citing "significant gaps" in validating the tests' usefulness, especially those sold directly to consumers.

Specialists advise anyone considering a gene test to:

• Consult a doctor or one of the nation's 3,000 genetic counselors to weigh pros and cons.
• Ask what the results will mean for siblings or children. How big is their risk, and do they want to know?
• Ask how accurate the test is, and if knowing you've got a risky gene allows you to take steps for better health or just worry.

"It's not of value unless you're going to do something to modify your health behavior," cautions Angela Trepanier of Wayne State University, president of the National Society of Genetic Counselors.

Stephanie Cone of Oak Harbor, Wash., illustrates the power of gene testing done right. She and her two sisters considered testing for about a decade as their mother beat back four cancer bouts — ovarian, colorectal and two separate breast cancers.

Years before their gene test, Cone and one sister had their ovaries removed. "The family history was clear," Cone said. A grandmother and great-grandmother had both died of ovarian cancer.

But with each of their mother's diagnoses, the sisters wondered if knowing the precise genetic risk might give them more ammunition, and help their own daughters later. A genetic counselor laid out possible scenarios: How would they feel if one sister escaped the gene risk? Would gene carriers get extra breast checks or choose breast removal?

Finally they took the plunge. All three shared their mother's BRCA1 mutation. That meant the final sister to get a hysterectomy also got extra testing that uncovered early-stage ovarian cancer, so she could undergo chemotherapy. And last December, all three sisters checked into the hospital for simultaneous mastectomies.

"I say to my children all the time, 'We're not afraid of cancer here,'" said Cone, whose 16-year-old daughter already said she'll be tested once she's old enough.

Conversely, not finding one particular gene for, say, breast cancer or diabetes doesn't mean you're off the hook for standard checkups; other genes could still sicken.

"The worry is that people say, 'Oh, I have a normal risk for these markers so I won't be tested ever,'" said UNC's McLeod.

Dr. David Altshuler of Harvard Medical School offers a scary example: He had a patient with a rare type of diabetes caused by a single gene mutation. One of her sons didn't inherit it — but he was at risk for more common Type 2 diabetes simply because he was overweight.

Yet, "he said, 'Now I'm through with diabetes,' and had some ice cream," Altshuler recalls.