Genome sequencing has its limits, researchers say

Apr. 03, 2012
Genome sequencing has its limits, researchers say
John Fauber | McClatchy-Tribune News Service

CHICAGO — Researchers have found that the increasingly popular form of disease prediction testing known as whole genome sequencing fails to provide solid insight into whether someone will develop a variety of common diseases.

The analysis showed that genome sequencing could warn of at least one disease, but most people would get negative results for the majority of the 24 diseases that were studied.

Yet those negative tests would not mean they are not at risk. Indeed, they still would have risks, although 20 percent to 50 percent less than the general population.

Genome sequencing could be useful for people who do not know their family disease history, said co-author Bert Vogelstein, a professor of oncology at Johns Hopkins University.

And down the road, such sequencing is likely to become valuable, revealing risks for cancer, heart disease and Alzheimer's disease, Vogelstein said.

But if someone already knows they have a family history of those diseases, they could be tested for a specific disease-causing genetic variation, rather than having their entire genome sequenced, he said.

Whole genome sequencing, which now costs about $7,500, is becoming increasingly popular, and its cost is expected to drop to as little as $1,000 in coming years. Genome sequencing involves cataloging all of the genes a person inherits from each parent. But the study in effect cautions against overreaching with the testing.

Vogelstein's paper, which was presented at the American Association for Cancer Research in Chicago, involved sequencing the genomes of 54,000 identical twin pairs. The researchers then used mathematical models to predict risk for 24 diseases.

Identical twins share the same genome and, theoretically, would have the same risk of developing various diseases such as cancer. However, most cancer is caused by the interplay of genetic mutations acquired after birth through environmental factors, lifestyle and random mistakes in genes that occur when cells divide, said co-author Victor Velculescu, a professor of oncology at Johns Hopkins University. So even though their sequencing was the same, their risk levels for common diseases are different.

As an example, researchers pointed to ovarian cancer.

Up to 2 percent of women undergoing whole genome sequencing would receive a positive test result for ovarian cancer, alerting them that they have at least a one in 10 chance of developing that cancer over their lifetime.

However, the other 98 percent who get a negative test are not guaranteed they will never get ovarian cancer.

They still would have a 1.3 percent chance of developing ovarian cancer sometime in their lives, compared with a 1.4 percent risk for the general population. In other words, the sequencing test results would be different, but the real-life experience would likely not.

"When it comes to cancer, it's genes, it's environment and it's bad luck," said Thomas Sellers, director of the Moffitt Research Institute in Tampa, Fla. Sellers was not involved in the study.

Another example is melanoma. While there are genes that convey higher risk for the disease, most people already know they are at increased risk, said Timothy Rebbeck, a professor of biostatistics and epidemiology at the University of Pennsylvania. Rebbeck also was not involved in the research.

People with red hair, freckles and who burn easy already know they should avoid the sun, he said. The value of genome sequencing for them would seem to be small.

Late-onset Alzheimer's disease, however, might be one of those diseases in which testing could be useful if people don't know their family history, Vogelstein said. And if they do know that Alzheimer's runs in their family, they could be tested for that specific gene variation - rather than having their whole genome sequenced. If they test negative, he said, they could be reassured that their risk would be small.

"For the vast majority, it (genome sequencing) will never become a crystal ball," he said. "I've met a lot of statisticians and the only thing they agree on is the risk of death is 100 percent."

Knowledge of one's entire genome can be valuable if it leads to beneficial changes in behavior, Rebbeck added.

"But the number of cases of that right now is small," he said.

John Fauber writes for the Milwaukee Journal Sentinel.