Mapping Your Future: Screening for Disease Risk

Genetic testing isn’t new. In the 1960s, doctors were able to test newborn babies for certain rare single-gene disorders, such as phenylketonuria (PKU), a rare metabolic disease that causes mental retardation. (PKU can be prevented with a special diet if it’s detected early, which was why it was critical to test newborns.)

In the 1970s, genetic testing changed dramatically as the number of tests expanded. The chromosomal basis for Down syndrome was discovered as well as the technique by which fetal chromosomes could be examined in amniotic fluid extracted from a pregnant woman’s uterus. Amniocentesis had arrived. Any fetal anomaly whose genetic basis was known could be detected from a sample of amniotic fluid. (The current rate of termination of pregnancies of Down syndrome fetuses is around 85%.)

In the 1980s and 90s, more tests were added. Among the most commonly tested for were cystic fibrosis, Down syndrome, fragile X syndrome, inherited thrombophilias, Klinefelter syndrome, neural tube defects, sickle cell disease, triple XXX syndrome, thalassemia, trisomy 13, trisomy 18, Turner syndrome. Screening for Tay-Sachs disease, Bloom syndrome, Canavan disease, familial dysautonomia, Fanconi anemia, Gaucher disease, mucolipidosis type IV, and Niemann-Pick disease was common for Ashkenazi Jews because of the higher incidence of these diseases in that population.

Currently there are more than 1000 genetic disorders for which testing is available (though sometimes only on a research basis). The great majority of these disorders are rare and testing is voluntary. Since the 1970s, however, state health departments have required mandatory testing of newborns, however, for certain serious congenital disorders that can often be lessened or prevented by prompt treatment.

The results of prenatal testing have raised a number of ethical issues for many people. There are societal concerns over the termination of pregnancies for conditions less severe, for example, than neural tube defects or Tay-Sachs disease (for which there is no cure and which results in a profound deterioration of mental and physical abilities usually results in death when the child is still a toddler). In vitro fertilization, in which multiple embryos are created and can be tested before implantation, makes such selection far easier, physically, and for many, ethically as well. LESS

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It took billions of dollars and several years to sequence the first complete human genome. But technologies rapidly advanced to the point where a person’s entire genetic profile can now be compiled in days for a thousand dollars or less. That may sound like a dream come true: understanding an individual’s unique genetic predisposition to disease will allow for targeting of both preventive care and treatment. According to proponents, it empowers individuals, giving them more tools to share with their physicians to use in making informed medical and behavioral decisions for better health.

But the current reality is far more complicated. What individuals get from these direct-to-consumer genetic testing service is a health report containing information about dozens of genetic risk factors for conditions such as heart disease, Alzheimer’s, addictions or obesity. The reports often include whether someone might suffer adverse reactions or not benefit from some specific medications, such as cardiovascular drugs. Some reports also offer genetic factoids like earwax type and sensitivity to the smell of sweat.

The problem, however, according to a report by The Hastings Center, is that there is far too little evidence on which to base these interpretations: “Genetic testing has moved with startling rapidity in the past half century from the obscure province of a small medical specialty dealing with extremely rare conditions to center stage in medicine and in the public imagination. Nevertheless, the promise of genetics has so far outstripped actual benefit, while concerns about societal risk have probably also outstripped actual harms. Whether the attention and financial investment in genetics will ultimately bear fruit is an open question.” LESS

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In the 1990s, researchers identified certain mutations of the genes referred to as BRCA-1 and BRCA-2 that appeared to increased person’s chance of developing cancer, particularly breast or ovarian cancer.*

That didn’t mean women who carried those mutations were absolutely destined to get cancer. “It’s important to realize that nearly every disease has both a genetic component and an environmental component,” Dr. Benjamin Wilfond of NIH’s National Human Genome Research Institute explains. “You can’t modify your genes, but you can modify your environment to help prevent some diseases.”

There are actually hundreds of different BRCA-1 and BRCA-2 mutations present in the general population, but most of them are either very rare or are not associated with any increased risk of cancer. And overall, only about 0.2% of the U.S. population carry any type of BRCA-1 or BRCA-2 mutation, which is why screening of these genes is not recommended for the general population.

But for a woman who is tested for mutations of these genes because of her family history, what do the screening results for mean? That’s difficult to say. The exact degree of risk is hard to quantify for an individual. A negative result does not mean that a woman will never develop cancer; only that she has the same lifetime risk of developing these cancers as the rest of the population, which is about 12% for breast cancer and 1.4% for ovarian cancer (it’s important to remember that 90-95% of breast cancers are not associated with a BRCA mutation). A positive result, on the other hand, does not mean that she will invariably develop breast or ovarian cancer, though her odds are increased (to about 60% for breast cancer and 15-40% for ovarian cancer, according to the National Cancer Institute). LESS

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