Wednesday, April 4, 2012

Genes are no crystal ball for disease risk

Deciphering a person?s genetic instruction book doesn?t predict medical future

Web edition : Tuesday, April 3rd, 2012

CHICAGO ? The human genetic instruction book is as lousy at predicting disease as an almanac is at predicting the weather, a prominent cancer researcher concludes from an analysis of the genetic data from thousands of pairs of identical twins.

A technological revolution has made deciphering genetic instruction books, called genomes, quicker and cheaper than ever before. Many scientists have touted the genome as a crystal ball for peering into people?s medical futures. But Bert Vogelstein of Johns Hopkins University School of Medicine wondered just how informative knowing a person?s genetic makeup could be.

So Vogelstein and his colleagues gathered medical data from 53,666 twin pairs from around the world. Identical twins share their genetic makeup, so looking at one twin?s health history may reveal what medical complications the other twin's genome has in store. The researchers did not decipher any of the twins' genomes but used used the medical data to develop a mathematical formula to predict the minimum and maximum risk of getting 24 different diseases, including several cancers, heart disease, diabetes and Alzheimer?s disease.

For all but four diseases, the genetic data would fail to determine who is likely to contract the condition in most cases, Vogelstein reported April 2 at the annual meeting of the American Association for Cancer Research. The results were also published online April 2 in Science Translational Medicine.

?Basically, you can still do better just by putting somebody on the scales and asking about their smoking history,? says Walter Willett, an epidemiologist at the Harvard School of Public Health who was not part of the study.

Under the team?s criteria, a test result was considered positive if it shows that a person has a 10 percent or greater chance of developing a particular disease. For most of the diseases, only a small fraction of people would get a positive test result, the researchers found.

For ovarian cancer, for example, only 1 percent to 23 percent of women who will eventually develop the cancer would get a positive result. So, most women who will get ovarian cancer would have received a negative test result.

That?s because genetics are only part of the story when it comes to determining health. Lifestyle, environment and random chance play a bigger role than genes, or work with genes, to cause or protect against disease.

But for the small number of people who do get a positive test result, such information could be very important. ?Even if the majority of individuals will receive negative test results, you don't know until you check,? says George Church, a Harvard geneticist and founder of the Personal Genome Project, an effort to catalog genomes and relate genetic variation to individual traits. ?It is analogous to fire insurance. You don't know in advance if you are in the majority who will not lose their house.?

Doctors, especially those who treat cancer, have already been through passionate debates about the value of genetic testing, says Olufunmilayo Olopade, director of the Cancer Risk Clinic for University of Chicago Medicine. The more doctors and scientists know about genomes, the better they can advise and treat patients, she said.

But Vogelstein said that he and his colleagues aren?t making a value judgment about the usefulness of genome sequencing. ?What we?re trying to do is simply introduce a reality check,? he said.

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