Nicole Aguirre, who’s just 13, has had 15 surgeries in the past two years. And that’s good news.
A rare, hereditary cancer syndrome called Von Hippel Landau, or VHL, has run rampant in her family for generations and has taken the lives of several relatives. With VHL, abnormal growth of blood vessels creates tumors, especially on the spinal cord, brain and eyes, often causing blindness.
Through a research grant, Nicole’s family members were genetically tested for VHL at the University of Texas Southwestern Medical Center during the past six years. As a result, all who have it are under constant medical surveillance.
Nicole is watched closely at Children’s Medical Center in Dallas by University of Texas Southwestern Medical Center pediatric oncologists and UT Southwestern retinal specialist Dr. Yuguang He. The goal is to catch any tumor early and to treat it immediately. So far, Nicole has her eyesight and continues to indulge her love of reading.
Eleven years ago, then-President Bill Clinton grandly announced the sequencing, or “first draft,” of the human genome. Clinton said the development would “lead to a new era of molecular medicine, an era that will bring new ways to prevent, diagnose, treat, and cure disease.” Scientists since have discovered hundreds of genetic variants, with risk associations ranging from heart disease to restless leg syndrome.
Clearly, there have been significant advances in DNA processing and basic scientific knowledge. However, research underscores the fact that disease has enormously complex causes and genes cannot be sifted easily to pinpoint the handful of offending mutations.
Dr. Angela Scheurele, a medical genetics physician who practices at Medical City of Dallas, says, “Twenty years ago, we used to think we were doing well when we confirmed a diagnosis one-third of the time. Now we can land one about one-half to two-thirds of the time. There are not enough superlatives to describe how far we’ve come in two decades. But no test is perfect.”
Francis Collins, director of the National Institutes of Health and author of a book about genetic research called The Language of Life: DNA and the Revolution in Personalized Health, says those expecting overnight results were bound to be disappointed. Genomics, he asserts, “obeys the First Law of Technology: we invariably overestimate the short-term impacts of new technologies and underestimate the long-term effects.”
After more than 10 years, the promise of translating the genome into clinical reality remains elusive. However, genetic testing can reveal life-saving information.
Genetic testing uses laboratory methods to analyze genes, which are inherited DNA instructions. The tests can identify increased risks for health problems, help in choosing a treatment, or assess response to medical treatment. People use genetic tests for sickle cell anemia, Down syndrome in fetuses, and cystic fibrosis. The predominant use, though, is for cancer.
The American Society of Clinical Oncology recommends genetic testing when a family history suggests a genetic susceptibility, when testing can be interpreted professionally, and when it can be used to diagnose a condition or influence medical management.
Linda Robinson, a genetic counselor supervisor at UT Southwestern, says up to 30 percent of cancer cases have a family component.
Only 5 percent to 10 percent of cancers have a major inheritable predisposition. The best known and most potent are the BRCA 1 and BRCA 2 genes.
A woman’s average lifetime risk for breast cancer is about 12 percent. However, the risk for a woman with one of the two BRCA genes rises five-fold, to about 60 percent. Similarly, a woman’s average ovarian cancer risk is less than 2 percent. With the presence of a BRCA mutation, however, it is 15 percent to 40 percent.
At UT Southwestern, counselors obtain a patient’s family history and assess risk factors such as environment, diet, and health behaviors. The information is entered into a program called GeneDirect, which was developed by UT Southwestern’s Dr. David Euhus. Its database predicts statistically the patient’s risk of developing cancer. The software is used in more than 4,000 medical centers in more than 75 countries.
The results dictate whether counselors recommend a genetic test. If so, a blood or saliva sample is sent for laboratory testing. If the results are positive, the patient is strongly encouraged to undergo earlier and more frequent screenings and to consider other measures.
Robinson says 90 percent to 95 percent of her patients change medical management based on a positive result. Many have their ovaries removed and about half have prophylactic mastectomies, especially if their cancer risk exceeds 50 percent.
Others may choose what is called chemoprevention. The drug tamoxifen has reduced the risk of developing or having a recurrence of breast cancer by about 50 percent, clinical trials show. According to a study published by Cancer in late March, tamoxifen prevented 29 cases of breast cancer and nine deaths in every 1,000 women treated.
Robinson calls high-risk patients “pre-vivors.” They are as-yet unaffected carriers of potent genes. Thanks to genetic testing, women can make informed choices prior to a cancer diagnosis.
Robinson says people often are in shock after finding out they have an elevated risk.
“Hearing they have a genetic predisposition to cancer is similar to getting a diagnosis. They usually are coming from a family that has
experienced cancer. Hearing you are at high risk is a powerful message, “ Robinson says. “The ultimate goal is to change health behavior. Once they see their risk in black and white, they are very motivated to change their destiny. They start exercising and eating better. They have seen family members suffer with this disease.”
Genetic testing is beneficial regardless of the results. A negative result brings relief and eliminates the need for extra checkups, screening, and possible surgery. A positive result can wipe away uncertainty and motivate women to take positive steps to minimize the risk.
Scheurele at Medical City, author of the book Understanding Genetics: A Primer for Couples and Families, says her practice is about 80 percent pediatrics, with the remainder split among prenatal and adult genetics.
She says pediatricians are more attuned to using genetics to make a diagnosis, while primary-care physicians are much less aware of the field so they refer cases far less often.
“Genetics has a mystique that prevents patients from seeking genetic counseling,” she says. “I don’t understand the fear. People deny themselves access to information.”
Scheurele offers an example of how pediatric genetic testing is beneficial. A couple with two healthy girls had a 3-month-old boy with a rare condition that disables the heart and muscles. Through genetic testing, Scheurele diagnosed Pompe disease shortly before the boy died. When the mother became pregnant again with another boy, the physician genetically tested the fetus and discovered the disease was not present. The family now has a healthy son.
“That’s the way it is supposed to work,” Scheurele says. “You get the answers from the first son to help them have a healthy second son.
“There is a mythology that women should not have prenatal genetic testing because of the fear of what they might do with the information,” she adds. “But it does not obligate anyone to take any action. The decision to have a test is separate from the decision of what you do after that test. If there is a problem with the child, parents can deal with it emotionally beforehand so the baby’s birth day is just a birthday—not a day you have to deal with the emotions of discovering an unexpected condition.”
Donnice Michel, a pediatrics genetic counselor at Children’s Medical Center of Dallas, says that when families receive a negative genetic test result, they tend to believe there is not a genetic basis for a condition. In fact, the test has only ruled out a specific cause.
Genetics professionals advise against using direct-to-consumer genetic tests sold in stores. Walgreens postponed selling the Pathway Genomics test last May after the FDA challenged its legality. The government appears to be deciding whether such tests are medical devices, which would require regulation, or simply consumer information.
A Government Accountability Office investigation found misleading test results and “egregious examples of deceptive marketing.” Federal officials sent real donors’ samples to four companies and posed as fictitious customers to inquire about results. According to the GAO, the companies produced different results for identical samples and told customers they had low risks for diseases they already had.
Robinson said the DTC tests are not that forthcoming about what they are testing and there is no standardization.
Scheurele calls them “entertainment. They don’t do a lot to find disease, [and] there are a lot of pitfalls and bad information without genetic counseling to explain them. You’ve got to recognize it for what it is.”
Some patients have too much faith in the predictive power of genetic tests. Robinson points out that 90 percent of breast cancer cases have no genetic basis. For most, family history and health behaviors are much more reliable predictors of future health.
Says Scheurele: “I can tell you more about your life expectancy if you tell me how old your parents were when they died, and if you smoke or wear a seat belt.”