This story has been updated from a version posted August 31 to provide more detail on the sample analysis process.
NEW YORK – Researchers from Australia's Monash University have launched a study to screen some 10,000 people aged 18-40 for nine genes that increase risk of hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia.
The four-year study, called DNA Screen, will serve as a pilot to test the scalability and feasibility of implementing a population screening program as part of routine medical care covered under Australia's public healthcare system.
The study joins other Australian efforts to incorporate genomics into public health initiatives. The government, for instance, recently established Genomics Australia, an agency tasked with supporting the integration of genomic medicine into Australia's healthcare system.
The conditions screened for in the study are considered both most penetrant in Australia and medically actionable. They are all adult-onset conditions that meet an evidence threshold for population where the risk is conferred by a single, high-risk pathogenic variant, whose effect is well known, such as BRCA1 and BRCA2 in the case of breast and ovarian cancers. Furthermore, intervention and risk management options supported by clinical guidelines are available for all these conditions.
"We've really stripped it down to the bare essentials so that there can be no accusation of over-screening, over-testing, or overreach," said Paul Lacaze, the study's principal investigator.
No moderate risk variants were included and variants of unknown significance are not reported, Lacaze added.
Michael Murray, a professor of genetics at Yale School of Medicine, who has himself conducted population genetics studies, called DNA Screen "exciting and important," and the conservative selection of the genes included in the study as being "based on sound data and rationale."
"Using DNA as a population screening tool through a public health system is something that many of us have talked about for some time," he said, "but it still needs to be modeled effectively, so I look forward to seeing the data from this 10,000-person pilot."
Lacaze noted that in contrast to many population genetics studies, which typically return genetic results to participants retrospectively, if at all, DNA Screen was designed to return them in the fairly quick time frame of 12 weeks, accompanied by a genetic counseling session courtesy of Australia's Garvan Institute to help participants understand their results.
This methodology, Lacaze said, stands at odds with what participants actually want, which is to have their genetic results as soon as possible in order to use them to proactively better their health.
"That's what people want," he said, "so we designed the study to deliver that exact thing to people in as timely a manner as possible."
Murray commented that while the 12-week turnaround time appeared reasonable, "ideally there should also be an ongoing periodic reanalysis of the participants' variant data since new information regarding variant reclassification within these nine genes is added almost daily to public records such as ClinVar."
At this stage, DNA Screen does not yet include such variant reanalysis.
"We hope that because we are only sequencing very well-known genes, supported by ClinGen expert panels, that variant reclassification and VUS will be minimal," Lacaze said.
He added, however, that reanalysis is a topic of ongoing discussion and the group has the technical capacity to reanalyze later, if needed or desired.
"At this stage," he said, "we're trying to deliver a screening test at a given time, with known and acknowledged sensitivity and specificity."
Lacaze and his collaborators are using traditional and social media to recruit participants, to whom they can send a saliva sample kit through the mail. Samples are processed and analyzed via a custom targeted capture and sequencing workflow using Illumina instrumentation at Monash University's Precision Medicine Laboratory, which Lacaze says has ample experience in working with large cohorts, as well as by the Biobanking Victoria facility.
"We got really good media attention in Australia," Lacaze said, "and as a result, we had over 10,000 people sign up in the first 24 hours," adding that another 10,000 have signed up in the week since.
"Incredible public response so far," he said. "The study shows the demand and the appetite for DNA testing that's out there. We're now trying to figure out how best to [deal with that] huge demand."
Despite the strong interest, Lacaze remains committed to demonstrating the study's proof of concept in 10,000 people, while planning how to scale it up in the future and what the time frame for doing so might be.
Murray noted that the study also offers the possibility of better understanding health risks in the Australian Aboriginal community, for which there appears to be little data.
"Understanding this subpopulation’s risk may be another interesting and important outcome of this work," he said.
While such an outcome isn't a stated objective of the study, DNA Screen has set a recruitment target of 3 percent of participants identifying as First Nations, in line with the proportion of Australians who identify as First Nations. The study also includes a First Nations Advisory Group, as part of an effort to meet this goal and to make the study as inclusive as possible.
"We understand the evidence on genetic risk varies across ancestral groups," Lacaze said. "We hope to add at least some evidence to help this situation in the future, [although] it is not the primary goal of our study."
DNA Screen has four years of funding from a $2.97 million grant through Australia's Medical Research Future Fund, a $20 billion long-term investment supporting Australian health and medical research.
"We're trying to do this in a highly ethical and responsible way that's evidence-based and designed to be compatible with our health system from the beginning," Lacaze said, adding that the study aims to "take all of the stakeholders on board with us on the journey including consumers, patient groups, clinicians, clinical services, genetic counseling researchers, epidemiologists, screening experts, and policy experts."