Newsweek: Unraveling Your DNA's Secrets - Do-it-yourself genetic testing

[Guest guest]

The dirty little secret comes out: " . . .But so far, very few genes

associated with major diseases have proved helpful in diagnosis or

treatment. " That's because it's really about stealth eugenics.

Lenny

Do-it-yourself genetic tests promise to reveal your risk of coming

down with a disease. But do they really deliver?

By Shute Posted Sunday, December 31, 2006

http://www.usnews.com/usnews/health/articles/061231/8genes.htm

Ellen had long thought that her death was preordained. Her

mother and aunt died of ovarian cancer, and her mother had breast

cancer, too. So the 54-year-old woman decided to get tested for the

BRCA genes that cause hereditary breast and ovarian cancer. " I wanted

to do the testing anonymously, " she says. " I didn't want it in my

medical records. " First Ellen called Myriad Genetics, the Salt Lake

City outfit that holds the patent on the BRCA genetic test. But Myriad

wouldn't test her without a doctor's signature, and her doctor would

only sign if she used her real name. (Ellen is an alias.) Then she

heard about DNA Direct, a San Francisco firm that sells the test to

the public. Under an assumed name, Ellen took the test in June, and it

came back positive for the BRCA mutation.

Ellen, who lives in New York, kept mum as she bought long-term

care insurance and increased her life insurance. " Those were a hard

three months, " she says now. " I was convincing myself that I really

had something. " She finally told her doctor, and in early December,

she had surgery to remove her ovaries, the only way to ensure that she

won't get ovarian cancer. Now she's talking with an oncologist and a

reconstructive surgeon about having her breasts removed. " I'm very

happy with DNA Direct, " she says. " They did excellent medical and

genetic counseling. "

In an era of inexpensive DNA analysis, genetic testing has

become absurdly simple: Buy a test online, and within a few days a kit

arrives in the mail. Rub the small brush on the inside of your cheek

for 30 seconds, pop it back in the prepaid envelope, mail it back, and

voilá! In a short time, you'll receive the truth about your genes. " A

lot of people didn't have access to these tests, " says Phelan, an

entrepreneur who founded DNA Direct in 2003 to sell tests for cancer,

cystic fibrosis, and other diseases. " This started really out of

seeing a very important need, "

Phelan says. " And if there's a need for it, maybe there's also a

good business. "

Real genes. But is good business also good medicine? In the past

few years, dozens of companies have started selling genetic tests via

the Internet. Some are real medical tests, for diseases including

breast cancer, celiac disease, and hemochromatosis. Others test real

genes but don't give information that's useful in making personal

health decisions.

" Many of the claims that are being made are quite fanciful, "

says Francis , director of the National Human Genome Research

Institute, who oversaw the project to sequence the human genome. " But

the fact that many of these tests have not yet reached the point of

rigorous scientific validation has not slowed down the interests of

consumers and of entrepreneurs. "

For years, scientists have predicted that medical care will

improve as they decode the ties between genes and disease. Just about

every week there's a " disease gene " discovery. But so far, very few

genes associated with major diseases have proved helpful in diagnosis

or treatment. A few genetic tests are used for diagnosing familial

breast and colon cancers.

Others are helpful in tailoring cancer treatments.

The first big application of genetics for medical treatment,

which the Food and Drug Administration is considering, will be for

warfarin, a blood thinner prescribed to prevent strokes. The test

identifies patients who have trouble metabolizing standard doses of

the drug, which can lead to bleeding in the stomach or brain. " The

genetic test is the most powerful indicator of where to start the

dose, " says , who directs the American College of

Medical Genetics. " What is much less clear is whether it would reduce

the number of bleeding problems. " In 2004, the ACMG said that at-home

genetic tests are potentially harmful. But it is reassessing that

stance, says , as it believes some forms, such as carrier

screening, are less problematic.

To investigate the quality and usefulness of direct-to-consumer

genetic tests, U.S. News tried six of them. Three were the same type

of tests used by doctors for celiac disease, hemochromatosis, and

breast cancer. Three others–for Alzheimer's disease, depression, and

glaucoma and macular degeneration–test genes associated with the

diseases but aren't used in medical practice. Our testers were U.S.

News staff members and their relatives. One staffer took a DNA sample

from his 3-year-old dog, Tate, a corgi mix. We found that the value in

diagnosing or predicting disease varies widely. Some could be helpful

in making health decisions, while others could be worthless or even

dangerous. And it's often hard to tell which is which. Our key findings:

Some tests that promise to reveal the risk of disease rely on

genes that aren't up to the task. The gene tested for Alzheimer's

disease, for example, indicates only increased susceptibility. And

there's nothing people can do to reduce that risk.

The advice some testing firms offer patients with the results

can be misleading. The test results often overstated the risk of

disease or were unclear about how to interpret that risk. References

to scientific research included with some of the results were outdated

or irrelevant.

Several tests offered generic preventive advice, such as " get

regular exercise. " Just two companies, DNA Direct and Denver's Kimball

Genetics, offered access to certified genetic counselors trained to

interpret and explain the results. Experts in the field say that

interpretation is crucial because the results are usually not black

and white.

Direct-to-consumer genetic tests are not regulated. The FDA does

not evaluate the safety and efficacy of at-home genetic tests. Some

are done in certified laboratories used by doctors and hospitals;

others are not.

In July, the Federal Trade Commission urged consumers to be wary

of the claims of DTC genetic testing.

Although there are now more than 900 genetic tests available to

doctors, most are used to screen for rare disorders like Duchenne

muscular dystrophy. For decades, scientists have been hunting similar

triggers for killers like heart disease and cancer. What they've found

are dozens of genes that interact with one another–and with

environmental effects like smoking. For instance, women with mutations

in BRCA genes have an 84 percent chance of getting cancer. But then

again, there's a 16 percent chance they won't.

Until now, most people who encountered genetic testing were

expectant women, who are routinely offered screening to see if they're

carriers of the genes for cystic fibrosis, sickle cell anemia, or

Tay-Sachs.

Amniocentesis and chorionic villi sampling tests can reveal

genetic disorders in a fetus. Newborns are screened for dozens of

genetic disorders like phenylketonuria, a metabolic disease, which are

treatable if detected early. Preimplantation genetic diagnosis is

increasingly being used to screen embryos for fatal disorders–and also

to pick the child's sex.

So if embryos can have a molecular crystal ball, why not

grownups? Alas, using genetic tests to predict eventual disease is a

lot tougher than diagnosing if the person already has a disease. " It

could account for the disease, or maybe it can't, " says Georgia

Wiesner, a geneticist at Case Western Reserve University. " There could

be other genes or other factors. "

With only a few diseases caused by a single gene, like

Huntington's disease, is it certain that a person who tests positive

will succumb.

Future peek. Still, there's no question that many people find

the chance to peek into the medical future irresistible.

Unfortunately, three of the tests that we analyzed that are marketed

as gauging the risk of major diseases relied on genes that don't

provide a clear view. The Alzheimer's test, sold for $150 by Graceful

Earth of Honolulu, examines the APOE gene.

One version is associated with an increased risk of Alzheimer's.

Our tester, a 41-year-old female, was told that she had APOEe3. Not

having APOEe4, the test results said, offered " moderate protection "

from Alzheimer's. But half of people with Alzheimer's don't have

APOEe4, and many people with it will never get Alzheimer's. " It

doesn't have a lot of value to the patient, " says Thies, vice

president of medical and scientific affairs for the Alzheimer's

Association, which recommends against using APOE for predictive

testing. Friedenberg, vice president of Graceful Earth, agrees

that having APOEe4 doesn't mean that someone will get Alzheimer's.

" We've gotten criticism from doctors, " he says. " But I think people

really want to know, especially if they'd had it in their family. "

Knowing a person is at increased risk, he says, could prompt him or

her to eat healthier. " What is the harm if someone starts increasing

their intake of antioxidants? Or fish oils? How is that going to hurt

them? "

Depression is another serious disease, estimated to affect 1 in

10 Americans. A depression risk test, sold by NeuroMark of Boulder,

Colo., for $125, says it tests for variations in a serotonin

transporter gene, 5-HTTLPR. In 2003, researchers found that people

with one version of the gene were more likely to become clinically

depressed after stressful events. Our tester, a woman in her 50s with

a family history of depression, was told she had a variant that makes

her less susceptible.

But 5-HTTLPR is only one of dozens of genes that may play a role

in depression. And five years from now, the genes linked to depression

will probably be totally different from those on the list now, says

Levinson, a professor of psychiatry at Stanford University who

is leading a huge national hunt for depression genes. Knowing those

genes may also make it easier to identify nongenetic factors. Studies

on twins, for example, suggest that about half of depression is caused

by genes, the other half by the environment. " Are there some people

for whom it's almost entirely genes? And others it's not genes? " asks

Levinson. " We just don't know. "

NeuroMark says the purpose of the test is " educational, " and it

is not attempting to assist doctors in diagnosing depression. " That

would be a reach, " says CEO Kim Bechthold, who notes the firm no

longer sells the depression test because of " enormous demand. " It

plans to reintroduce the test in mid-2007.

Fear of disease is a powerful motivation to seek out genetic

testing, and that's certainly the case with blindness. Age-related

macular degeneration and glaucoma are two leading causes in people

over age 55. Macular degeneration causes deterioration in the retina;

with glaucoma, excess pressure within the eye damages the optic nerve.

A test for macular degeneration and glaucoma, sold for $99.95 by

CyGene Laboratories of Coral Springs, Fla., looked at three variants

in the myocilin gene. But those are just three of the 80 to 100

myocilin changes associated with glaucoma.

Our tester, a 37-year-old woman with abnormally high pressure on

glaucoma tests, got this news: " You do not have an increased risk for

developing Primary Open Angle Glaucoma over the general population. "

That may or may not be true. " It's just too small a slice, " says Janey

Wiggs, an ophthalmologist at Harvard Medical School who is leading a

national study of the genetics of glaucoma. " You could easily miss a

mutation that could be related to very severe glaucoma. " So far, Wiggs

says, genetic testing is useful only in patients with early onset of

glaucoma and a family history of the disease, something that our

tester doesn't have. The best way to screen for disease, Wiggs says:

Go to the eye doctor. Munzer, CEO of CyGene, says that " we

could do a comprehensive vision panel, but nobody would be able to

afford it. " His company's test, he says, is not definitive, but " it's

like chicken soup–it won't hurt you. "

He agrees that regular eye exams are the best screening tool.

When considering do-it-yourself genetic testing, customers need

to be certain the tests are performed properly. " People should be

aware that there is no regulation of the quality of the tests that are

being sold over the Internet, " says Kathy Hudson, director of the

Genetics and Public Policy Center at s Hopkins University. " They

may not be certified labs, and even if they are, the regulations for

laboratory quality really are general and have minimal standards. They

don't assess whether a laboratory is able to accurately do genetic tests. "

The FDA, which approves drugs and medical devices, deems genetic

tests " services, " devised by the labs that perform them. And the

Centers for Medicare and Medicaid Services, which regulates medical

laboratories under the Clinical Laboratory Improvement Amendments, or

CLIA, has balked at creating special oversight for genetic tests. At a

minimum, people ordering genetic tests should ask if the laboratory is

certified under CLIA. " I would also look for a lab that's

participating in the College of American Pathologists or ACMG

proficiency testing, " says ACMG's ..

Four of the testing companies we used, DNA Direct,

HealthCheckUSA, Kimball Genetics, and NeuroMark, use CLIA-certified

labs. CyGene plans to apply for CLIA certification this month, Munzer

says.

We sent CyGene a sample of DNA from Tate the dog. The results

reported that Tate had a " moderately elevated risk of macular

degeneration. "

Geneticists say dog DNA is similar enough to human DNA to return

a result.

But dogs don't get macular degeneration.

A 2006 Government Accountability Office study found that

nutrigenetic tests, which offer nutritional advice to reduce disease

risk–based on your DNA–failed to do so. " Clearly consumers are being

misled by this modern-day snake oil, " Sen. Gordon , a Republican

from Oregon and chairman of the Special Committee on Aging, says of

the nutrigenetic tests. and Massachusetts Democratic Sen.

Kennedy plan to introduce legislation aimed at imposing tighter

controls on all genetic tests.

Patient privacy. Despite the paucity of oversight, some clients

say the tests are quite literally just what the doctor ordered. After

, 37, of North Carolina had a stillbirth and a miscarriage,

her doctor suggested that she take a test for Factor V Leiden, a

hereditary disorder that boosts the risk of blood clots. But he

proposed that she order the test through DNA Direct so that the

results wouldn't be part of her medical record. tested positive.

" No one wants to have bad news, "

she says, " but I felt somewhat liberated by knowing it. "

Almost all states have laws offering some protection against

genetic discrimination by medical insurers. Federal legislation

prohibiting genetic discrimination in employment or insurance has

failed to pass Congress. " We get two or three calls a month from

people who have lost their jobs or lost their insurance, " says Sharon

Terry, president and CEO of the Genetic Alliance, a consumer advocacy

group.

The DTC genetic testing firms aren't required to protect patient

privacy under federal law, as hospital and healthcare facilities must.

And there is no guarantee that the firms won't sell or share medical

results with insurers or another company. The privacy question cuts

another way. A person who hides test results could also miss out on

important healthcare–say, more careful reading of mammograms for

someone who's BRCA-positive. " It makes for an incomplete medical

record that will not be transportable, " says Wiesner. " I would submit

that that's not modern medicine. "

For most people, the odds of having a hereditary disorder are so

small that testing doesn't make sense. Elissa Levin, a genetic

counselor and clinical director of DNA Direct, says that 40 percent of

their clients test positive, a much higher number than would be found

in the general population. " The vast majority of people who are

testing are testing due to personal diagnosis, family history, or 1 in

5 have a known family mutation, " she says. " It's not the worried well. "

DNA Direct's most popular test is its $199 screening for

hemochromatosis, which elevates iron in the blood and can lead to

liver cancer. Ever since a gene that causes the disease was detected

in 1996, doctors have debated widespread screening. ,

president of the American Hemochromatosis Society, encourages people

who contact her to use DTC tests and thinks that everyone should be

screened for the disease, which killed her mother. But a National

Institutes of Health study of almost 100,000 people in 2005 found the

correlation between gene and disease not strong enough to be useful as

a screening tool. The U.S. News staffer, who took the test through

HealthCheckUSA, had no family history and came up negative. " Some

people have cirrhosis and liver cancer, and some people have the same

genetic profile and don't even have iron overload, " says , a

gastroenterologist at the University of Western Ontario who led the

NIH study.

Genetics is notoriously confusing, and most people need help

interpreting test results. Most primary care doctors never studied

genetics in medical school, and there are only about 800 U.S.

physicians board-certified in genetics. About 3,000 genetic counselors

have master's degrees, but they aren't doctors and thus can't give

medical advice.

Annette , president of Kimball Genetics, is both a

geneticist and a certified genetic counselor, and she believes that

counseling and interpretation are essential for both patients and

doctors. She requires customers to give a healthcare provider's name

and faxes them the results.

Our celiac disease tester, a 38-year-old male who has irritable

bowel syndrome, called the counselors at Kimball because he couldn't

decipher the written results. " A DQA 1*05 allele (*0501 or *0505) was

detected but neither of the DQB1*02 alleles (*0201 or *0202) was

detected, " they read in part. The counselor, who said she had a

master's in genetic counseling, spent 20 minutes talking with him by

phone. He said she explained that the test didn't rule out celiac,

which is caused by an autoimmune reaction to gluten in food, but it

didn't definitively diagnose celiac, either. A third of the population

had this genetic pattern, she said, but only about 1 percent has

celiac. She suggested the tester talk with his doctor about a blood

test that would detect gluten antibodies. She also suggested, twice,

that he buy the test from Kimball, raising the question of whether her

focus was on interpreting tests or selling them. " She was just making

it convenient for him, " says . " We would never say anything that

is not medically indicated. "

To gauge how phone counseling compared with face-to-face

guidance, U.S.

News asked Deborah Nagler of Teaneck, N.J., to call DNA Direct.

Nagler had a double mastectomy in 2002 at age 50, after learning she

had a BRCA mutation (her sister, mother, and aunt died of breast

cancer). The DNA Direct counselor called her at home after she filled

out an online form.

" I found her to be very empathetic, very knowledgeable, and that

there was relative parity with the face-to-face experience I had, "

says Nagler. " The counseling piece is really, truly critical. It's a

personal and emotional upheaval to receive the news. "

Nagler worries about her two daughters, both in their 20s. " I

could be delivering death sentences to my children, and to my

children's children. "

With more access to genetic testing, more families will face

these struggles. The hope is that they will do so armed with real

medical insight, not hype.

A BRAVE NEW WORLD

Some genetic tests are already in wide use. Others have yet to

fulfill their promise. Tests include:

r screening. Pregnant women can be tested for mutations

they can pass on to their children.

Prenatal screening. Tests that pull a fetus's genes from

amniotic fluid or chorionic villi can detect disorders.

Newborn screening. All babies are tested right after birth for

treatable diseases.

Forensic. DNA can identify criminal suspects or victims, as well

as establish paternity.

Predictive. A few tests can help gauge the odds of having a

familial version of a disease.

Diagnostic. Genes can reveal or confirm inherited diseases such

as sickle cell, as well as rare disorders.

Nutrigenomic or nutrigenetic. Sold as offering customized

nutritional advice, but they're questionable.

Pharmacogenetic. Doctors now use genes to tailor cancer

treatments to the individual patient. More are in the works.