Genetic tests offer early warnings for disease, for better or worse

relder@newsobserver.comMay 26, 2013 

  • Genotyping versus gene sequencing

    Genotyping is a process that provides information on specific variants based on examination of selected segments of genes.

    Gene sequencing examines longer strings of DNA for known variants but also may identify individually unique mutations.

    The first complete human gene sequencing took place during the Human Genome Project, which ran for 10 years and was completed in 2003. There are more than 20,000 individual genes in the human body.

    Sequencing genes may costs thousands of dollars, compared to about $100 for a direct-to-consumer genotyping report on more than 250 known variants.

    Gene sequencing may be preferred by doctors seeking specific medical information for patients or before prescribing more individualized medical treatment. Prices for gene sequencing are expected to drop through ongoing advancements in technology.

    Source: American Cancer Society; Coriell Institute for Medical Research;

Marla Dansky is scheduled for two rounds of surgery this summer, shortly after she completes chemotherapy treatments for a tumor in her left breast.

Her first operation at Duke Cancer Center will remove both breasts. A second will take out her ovaries and uterus, which are not cancerous but are likely to develop the disease, based on genetic tests that show she carries a faulty BRCA1 gene.

“It’s the best pre-emptive strike that I have,” Dansky, 40, said of her decision to undergo a complete hysterectomy in addition to bilateral breast surgery. “My plan is to ‘do cancer’ once, and do it right the first time.”

The strong link between the BRCA1 gene and cancer, as well as the option to sidestep much of the risk through elective surgery, grabbed headlines recently when actress Angelina Jolie made public her decision to undergo a double mastectomy.

But the procedure isn’t only available to movie stars. More than a third of women who test positive for BRCA1 are choosing preventative surgeries – largely because the gene mutation raises the typical 10 percent risk of female breast cancer to something closer to 80 percent, according to the National Cancer Institute.

Screening for breast cancer is now one of more than 1,000 genetic tests available to evaluate health risks. Such tests offer unprecedented opportunities to take steps to avoid serious illness in many cases, but they pose dilemmas for patients facing a high risk for diseases with no known cure.

Medical laboratory testing for genetic conditions can be expensive – typically running about $3,000 for BRCA1. Because the disease is so expensive to treat and can be fatal, the cost for gene testing is often covered by insurance for women who have a strong family history of breast cancer and have been referred for testing by their doctors.

As the first company to isolate the individual BRCA1 and 2 genes, Myriad Genetics holds a patent for this test. The Salt Lake City-based company is facing a lawsuit over the gene patent, a case that is now before the U.S. Supreme Court. A ruling is expected in June.

Individuals seeking more general clues to their genetic profiles are turning to direct-to-consumer testing companies. A number of companies offer to scan blood or saliva samples for indications of risk for common diseases such as macular degeneration or diabetes, as well as more serious conditions such as cancer or Parkinson’s disease.

One such testing company, the Web-based 23andMe, evaluates genetic indicators for health, ancestry and other traits using saliva samples sent in by customers, said company spokeswoman Catherine Afarian.

In 2007, when the testing was first offered, the service produced 14 reports for $999. Now more than 240 reports are available for $99, Afarian said.

“It’s a reflection of the amount of research that is being done in the field of genetics,” she said.

Their BRCA test looks for three of the most common markers, although there are more than 100 possible BRCA gene mutations that can occur, Afarian said.

All results are provided through a secure internet portal, and customers have the option of declining to view certain data sets, such as those indicating an elevated risk of Alzheimer’s disease or cancer.

“We try to make it clear that some information could be useful or interesting, and some they may not know how to respond to,” Afarian said. “Once you know that information, you can’t unlearn it.”

Kristy Lee, a certified genetic counselor at the UNC Cancer Center, said she has counseled patients who have had difficulty interpreting their commercially obtained results. Some seem overly frightened by slight elevations in risks with little statistical significance, while others are shocked to learn they may someday face serious disorders with no known treatment.

“I don’t think people understand the gravity of the information they can get,” Lee said. “While a lot of the direct-to-consumer testing is just fun stuff, like ancestry or whether you like Brussels sprouts, the medical stuff, which looks at a bunch of markers across different genes, can be easily misinterpreted.”

BRCA and cancer risk

When working correctly, the breast cancer susceptibility genes BRCA1 and BRCA2 prevent unchecked cell growth. But mutations can impair that function and raise the risk of cancer.

BRCA mutations increase the likelihood of cancer in both breasts and of developing more than a single type of cancer, according to the American Cancer Society. Also associated with the BRCA mutations are cervical, uterine, pancreatic, colon, stomach, gallbladder and bile duct cancer, as well as melanoma.

Cancers in women with BRCA1 mutations also are known to be less responsive to typical chemotherapy treatments.

“When I see patients who have genetic risk factors as well as family history that suggests a higher risk, the question eventually arises as to whether to step in and prevent cancer by prophylactic surgeries,” said Elizabeth Campbell, a medical oncologist who sees patients in Raleigh at the Cancer Centers of North Carolina.

A surgical procedure to combat a disease that hasn’t yet developed may seem extreme, but it can be the best option for patients with a BRCA mutation, said Gary Lyman, a professor in the division of medical oncology at Duke University Medical School.

“It’s the most definitive way to reduce risk,” Lyman said. “For those who don’t want to take that step, there are medications and other preventative options. Careful screening with MRI starting in the early to mid-20s can catch breast cancer in most people before it spreads throughout the body.

“But those with an 80 percent chance of developing the disease may choose not to live with that chance.”

When an oncologist suggested to Dansky that she consider preventative surgery after her mother and two aunts were diagnosed with breast cancer, she was resistant.

“I said ‘Hold on a minute!’ ” she recalls. “I still had my tonsils and appendix. I’m not the type of person who goes volunteering for surgery. Instead, I went for a mammogram to confirm that I was fine.”

After the mammogram revealed a tumor and a biopsy confirmed that it was cancer, Dansky began to soften toward the idea. But first she underwent genetic testing that confirmed the BRCA1 gene.

“Because my ancestry is Ashkenazi Jewish, I wasn’t really surprised by the results,” she said.

In the overall population, BRCA1 and 2 mutations occur in 1 in 500 people. For some specific groups, however, the odds are much greater, among them descendants of the Ashkenazi Jews of Eastern Europe, who have a 1 in 40 chance of having a BRCA1 mutation.

Doctors estimate that Dansky, who works as a development director for a nonprofit in the Triangle, will cut her lifetime risk of breast and other types of cancer from about 80 percent to less than 10 percent by having both breasts, her ovaries and uterus removed.

Dansky said her two children, Jacob, 10, and Paige, 5, weighed heavily in her decision.

“My first thoughts when I was being diagnosed with cancer were that I don’t want to miss their growing-up years,” she said. “I don’t want to miss a minute – and I certainly don’t want to miss the rest of their lives.”

Putting things in perspective

Tests to determine BRCA mutations were developed in the mid-1990s and have been in widespread use by oncologists since the early 2000s, with other physicians joining over the past five years.

In some ways, the availability of genetic testing may be running ahead of the curve of medical practice.

“Even most general practitioners don’t have a good idea of what genetic testing can do right now,” said Lee, the genetic counselor at UNC.

And then there are issues of privacy. The federal Genetic Information Nondiscrimination Act prevents health insurance companies from denying health coverage based on genetic test results. But other areas such as employment law and life insurance coverage have not yet been addressed, said James Evans, professor of genetics and medicine at UNC.

Despite ongoing concerns, gene testing is already becoming a game changer for the practice of medicine. Certain tests will eventually make their way into routine standards for care, as mammography and colonoscopy have done over the past few decades, Evans said.

Evans and Andrew Olshan, an epidemiologist at the UNC Gillings School of Global Public Health, co-authored an article in a recent edition of Genetics in Medicine calling for more research into the best way to incorporate genetic screening into medical practice, along with public policies to maximize benefits and manage costs.

Their proposal stresses the need to target serious diseases that may be prevented, treated or cured based on genetic information. Colorectal cancer, breast cancer, hereditary heart disease, thyroid cancer and certain types of aneurysms are among them.

“The underlying concept is that people are walking around carrying mutations that dramatically predispose them to severe diseases that are entirely preventable if you know about them,” Evans said. “Right now, it’s like the canary in the coal mine. Without genetic testing, you are just waiting for someone in your family, or you, to develop one of these diseases.”

Elder: 919-829-4528

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