newsweek: Unraveling Your DNA's Secrets - Do-it-yourself genetic tests

[Guest guest]

Unraveling Your DNA's Secrets

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.

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