The Future
The lack of a national VA contract with outside laboratories for genetic testing means that each facility has to negotiate its own contract, which is a wasteful duplication of resources that needs to be addressed. Beyond this parochial concern, GCRA is undergoing a revolution in diagnosing and managing cancer risk. In the past, a careful family history was followed by selected single gene testing for mutations, using Sanger sequencing. However, many laboratories are now offering multigene testing using next-generation sequencing that can look at multiple genes, all the way up to whole genome sequencing. Current estimates for the actual cost to the laboratory for a whole genome using next-generation sequencing is about $1,000.
A number of laboratories also have been offering multigene panels for testing in patients with familial cancer syndromes. The genes in these panels include those with a well-documented association with known cancer syndromes as well as other genes where mutations may confer only a modestly increased risk. Furthermore, new genetic syndromes and new genes associated with known syndromes are being reported yearly.
This revolution in technology and the virtual explosion in the amount of data generated have raised as many questions as answers. 11 One joke in the genetic testing community goes: “$1,000 genome, $100,000 interpretation.” Among the remaining issues are how to counsel patients about the possible results from multigene testing, including the possibility of results that may be applicable to noncancer-related diagnoses; what to do about the unanticipated actionable finding (incidentaloma); how to interpret and treat a patient whose gene test results are at odds with the clinical family history; how to treat patients whose panel returns with a mutation in a gene that has only a minor increased risk for the cancers; how genes with modestly increased or decreased risk singly or in combination may modify highrisk gene expression; and how to address variants of unknown significance.
A general consensus has emerged that these questions will need much more research correlating genetic and clinical data to answer. As a result, many leading researchers have set up multi-institutional, international collaborative groups directed at specific syndromes, which pool data from many investigators to answer questions beyond the capability of any single investigator or group. These big data collaborative studies are already beginning to publish early results and seem to represent the future of genetic cancer risk assessment, a field that is at once dynamic, exciting, and confusing. 4
A major question is whether and how the VA can cooperate with these international consortia. The VA has particular concerns about confidentiality based on past experience, but it also has a unique group of patients who could provide valuable contributions to our knowledge about genetic markers for disease, including cancer. A method for the VA system to provide data to collaborative groups who are advancing our knowledge of the genetic risk factors for cancer while protecting the confidentiality of veterans could provide a model for collaboration between the VA and non-VA health care systems.
Author disclosures
The author reports no actual or potential conflicts of interest with regard to this article.