Screening the genomes of healthy people may give important clues about their cancer risk, according to a study that suggests advanced DNA technology might be employed early in a patient’s health assessment.
Among 572 people who underwent a broad analysis, 12 were found to have genes that put them or their children at elevated risk of dangerous tumors, according to the report from researchers at the U.S. National Human Genome Research Institute in Bethesda, Maryland. Eight of the participants had no family history of cancer that doctors normally look to for signals of heightened susceptibility to malignancies, the study said.
The research, released today by the American Journal of Human Genetics, highlights the role that sequencing machines made by Illumina Inc. (ILMN:US) and Life Technologies Corp. (LIFE:US) may play in alerting healthy individuals to their risk of disease. The machines can decipher swaths of human DNA in hours, giving massive amounts of information about inherited traits.
“The current medical approach for finding susceptibility to disease requires that you or your family members have the condition or have died of it,” said Leslie Biesecker, chief of the genetics disease research branch at the Human Genome Research Institute, in a telephone interview. “This suggests that it doesn’t have to be that way, that we can find susceptibility before all that suffering.”
Biesecker’s study, called ClinSeq, sequences all the genes in participants’ DNA to find clues to health and disease. About 1 percent of the human genome, the reproductive code found in each cell, is composed of genes, which are the blueprints for making proteins.
The researchers screened 37 genes in participants’ DNA for changes that have been linked to cancers. The screen yielded 334 variants of “potential clinical importance,” most of which were associated with unknown cancer risk.
Eight participants were found to have gene mutations that significantly elevated their risk. Seven had changes in the BRCA1 and BRCA2 genes that sometimes appear in families affected with high rates of breast and ovarian cancer, the study said.
Another participant had a mutation in a gene called SDHC, which has been linked to head and neck tumors that sometimes cause severe nerve damage. This person, along with three of those with BRCA1 and BRCA2 mutations, had no family history of the cancers related to these genes.
“This demonstrates that there’s fairly high frequency of useful information that one can gain from the whole exome or whole genome,” said Robert Nussbaum, chief of the division of medical genetics at the University of California, San Francisco.
Genetics researchers have debated whether it’s worthwhile to look across the span of the genome on the chance that a dangerous mutation may be present in a person with no family history of disease, Nussbaum said.
“The paper shows that we can detect mutations that everyone would agree that a patient and doctor should be alerted to,” he said in a telephone interview.
Scientists using DNA sequencers to investigate the human body are also struggling with how to handle the explosion of genetic information, and when to share it with research participants. Thousands of people who volunteer for research studies involving DNA testing agree not to receive the results.
Because the implications of genetic information can be difficult to explain, many of the panels that oversee human research, called institutional review boards, set guidelines for studies that discourage unexpected results, often called secondary findings, from being communicated to subjects.
Geneticists are asking whether there should be a minimum set of gene mutations examined and reported back to doctors when seen in anyone whose DNA has been sequenced, said Robert Green, a Harvard Medical School geneticist. These would be genes that are well-understood and have a strong health impact.
“The question is whether you should report these secondary findings, and this paper supports it,” he said in a telephone interview. “They found real cancer-related variants in people who didn’t think they were at risk for cancer.”
Results from the institute’s study were confirmed and returned to the participants by clinical geneticists, doctors who are trained to interpret genetic information and share it with patients and other caregivers. All received appropriate referrals, prevention information and counseling.
Four subjects with high-risk colon cancer genes were carriers of recessive mutations that won’t affect them, but may affect their children, researchers said. Those findings will be returned to the participants later as part of the continuing project.
The researchers also will study how patients react to the information they’ve received over time, Biesecker said. These and many other issues must be resolved before widespread genetic risk assessment can be used in larger populations, he said.
“While this opens the door to wider possibilities, we’ll need to scale it up,” Biesecker said. “You probably need to think of first going from 500 people, like we did, to 5,000 people.”
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