In an extended phase II clinical trial of 500 patients with different types of stage 4 solid tumors who had responded to chemotherapy, a maintenance regimen with low-dose interleukin-2 and 13-cis retinoic acid has shown unexpected 5-year survival rates.

A study in Science Translational Medicine (published online 2012 Apr 2) by Johns Hopkins investigators indicates that whole-genome sequencing will not provide solid predictive information for most people about their risk for many common diseases, including cancers. Furthermore, negative genome test results may make people complacent about taking steps to detect or prevent disease.

“We're definitely not saying that whole-genome sequencing is useless,” says Bert Vogelstein, MD, co-director of the Ludwig Center for Cancer Genetics at Johns Hopkins in Baltimore and a senior author of the study. “We're just trying to show how useful it will be.”

To investigate the predictive potential of whole-genome sequencing, Vogelstein's team combed through data on thousands of monozygotic twin pairs entered in the Swedish Twin Registry, Danish Twin Registry, Finnish Twin Cohort, Norwegian National Birth Registry, and the National Academy of Sciences–National Research Council World War II Veteran Twin Registry.

“If the genome were the determining factor for common diseases, then the prevalence of a specific disease in an individual whose twin has that disease can be used to determine how well whole-genome sequencing could predict an individual's disease risk,” explains Vogelstein.

The researchers collected information on the incidence of 24 common diseases, including 9 types of cancer. Using sophisticated mathematical models that they developed, the researchers calculated the ability of whole-genome sequencing to predict the risk of each disease based on typical thresholds that doctors use in decisions to start preventive or therapeutic measures.

Their analysis shows that whole-genome sequencing could alert most people to an increased risk of at least 1 disease, signaled by a positive test result, but most people would get negative test results for the majority of diseases studied, failing to forewarn them of the disease they may ultimately develop.

In the case of ovarian cancer, about 2% of women would test positive, defined here to mean that they have a 10% increased risk of developing the disease. That means 98% of women would receive a negative test result, meaning they are not at excess risk—their risk of developing ovarian cancer is the same as in the general population.

“It would be nice if the test would say they are risk-free, but that's not the case,” says Vogelstein. “It's not going to give them a ‘get-out-of-jail-free card.’ Cancers are largely the result of non-hereditary contributions.” For example, obese women are more likely to develop ovarian cancers.

Vogelstein notes that whole-genome sequencing will be extremely valuable in some cases, such as in families with a strong history of cancer. “But for most people, it won't show risk much different from the general population,” he says.

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