Half of the people tested were unaware of their genetic risk for contracting the disease
Existing clinical laboratory genetic screening guidelines may be inadequate when it comes to finding people at risk of hereditary breast-ovarian cancer syndromes and Lynch syndrome (aka, hereditary nonpolyposis colorectal cancer). That’s according to a study conducted at the Mayo Clinic in Rochester, Minn., which found that about half of the study participants were unaware of their genetic predisposition to the diseases.
Mayo found that 550 people who participated in the study (1.24%) were “carriers of the hereditary mutations.” The researchers also determined that half of those people were unaware they had a genetic risk of cancer, and 40% did not meet genetic testing guidelines, according to a Mayo Clinic news story.
The discoveries were made following exome sequencing, which the Mayo Clinic news story described as the “protein-coding regions of genes” and the sites for most disease-causing mutations.
“Early detection of genetic markers for these conditions can lead to proactive screenings and targeted therapies, potentially saving lives of people and their family members,” said lead author Niloy Jewel Samadder, MD, gastroenterologist and cancer geneticist at Mayo Clinic’s Center for Individualized Medicine and Comprehensive Cancer Center.
“This study is a wake-up call, showing us that current national guidelines for genetic screenings are missing too many people at high risk of cancer,” said lead author Niloy Jewel Samadder, MD (above), gastroenterologist and cancer geneticist at Mayo Clinic’s Center for Individualized Medicine and Comprehensive Cancer Center. New screening guidelines may increase the role of clinical laboratories in helping physicians identify patients at risk of certain hereditary cancers. (Photo copyright: Mayo Clinic.)
Advancing Personalized Medicine
“The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC (hereditary breast and ovarian cancer) and LS (Lynch syndrome),” the authors wrote in JCO Precision Oncology.
For the current study, Helix, a San Mateo, Calif. population genomics company, collaborated with Mayo Clinic to perform exome sequencing on the following genes:
BRCA1 and BRCA2 genes (hereditary breast and ovarian cancer).
Mayo/Helix researchers performed genetic screenings on more than 44,000 study participants. According to their published study, of the 550 people who were found to have hereditary breast cancer or Lynch syndrome:
387 had hereditary breast and ovarian cancer (27.2% BRCA1, 42.8% BRCA2).
163 had lynch syndrome (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2, and 0.2% EPCAM).
Participants recruited by researchers hailed from Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla.
Minorities were less likely to meet the NCCN criteria than those who reported as White (51.5% as compared to 37.5%).
“Our results emphasize the importance of expanding genetic screening to identify people at risk for these cancer predisposition syndromes,” Samadder said.
Exome Data in EHRs
Exomes of more than 100,000 Mayo Clinic patients have been sequenced and the results are being included in the patients’ electronic health records (EHR) as part of the Tapestry project. This gives clinicians access to patient information in the EHRs so that the right tests can be ordered at the right time, Mayo Clinic noted in its article.
“Embedding genomic data into the patient’s chart in a way that is easy to locate and access will assist doctors in making important decisions and advance the future of genomically informed medicine.” said Cherisse Marcou, PhD, co-director and vice chair of information technology and bioinformatics in Mayo’s Clinical Genomics laboratory.
While more research is needed, Mayo Clinic’s accomplishments suggest advancements in gene sequencing and technologies are making way for data-driven tools to aid physicians.
As the cost of gene sequencing continue to fall due to improvement in the technologies, more screenings for health risk factors in individuals will likely become economically feasible. This may increase the role medical laboratories play in helping doctors use exomes and whole genome sequencing to screen patients for risk of specific cancers and health conditions.
Studies into use of population-level genomic cancer screening show promising results while indicating that such testing to find evidence of increased cancer risk among non-symptomatic people may be beneficial
In another example of a government health system initiating a program designed to proactively identify people at risk for a serious disease to allow early clinical laboratory diagnosis and monitoring for the disease, cancer researchers at Monash University in Australia have receive a $2.97 million grant from the Medical Research Future Fund (MRFF) to study ways to “identifying people who are living with a heightened cancer risk who would ordinarily be informed only after a potentially incurable cancer is diagnosed.”
According to a Monash news release, the researchers, led by Associate Professor Paul Lacaze, PhD, Head of the Public Health Genomics Program at Monash University, plan to use the award to develop a “new low-cost DNA screening test which will be offered to 10,000 young Australians. The new approach, once scaled-up, has the potential to drastically improve access to preventive genetic testing in Australia, and could help make Australia the world’s first nation to offer preventive DNA screening through a public healthcare system.”
Called DNACancerScreen, the clinical genetic test will be offered to anyone between the ages of 18 and 40, rather than to a select group of people who have a family history of cancer or who present with symptoms. The Monash scientists hope to advance knowledge about the relationship of specific genes and how they cause or contribute to cancer. Such information, they believe, could lead to the development of new precision medicine diagnostic tests and anti-cancer drug therapies.
Gap in Current Cancer Screening Practices
The DNACancerScreen test will look for genes related to two specific cancer categories:
Hereditary Breast and Ovarian Cancer Syndrome is associated with an increased risk of developing breast, ovarian, prostate, and pancreatic cancers, as well as melanoma. Lynch Syndrome is associated with colorectal, endometrial, ovarian, and other cancers.
Currently, screening practices may miss as many as 50-90% of individuals who carry genetic mutations associated with hereditary breast and ovarian cancer, and as many as 95% of those at risk due to Lynch Syndrome, according to the Monash news release.
But currently, only those with a family history of these cancers, or those who present with symptoms, are screened. By targeting younger individuals for screening, Lacaze and his team hope to give those at risk a better chance at early detection.
“This will empower young Australians to take proactive steps to mitigate risk, for earlier detection, surveillance from a younger age, and prevention of cancer altogether,” Lacaze said in the news release.
Along with the possibility of saving lives, Associate Professor Paul Lacaze, PhD (above), Head of the Public Health Genomics Program at Monash University, expects that the screening program will have an economic impact as well. “This type of preventive DNA testing will not only save lives, but also save the Australian public healthcare system money by preventing thousands of cancers,” he said. There’s evidence to back up his statement. In 2019 he led a team that published a study, titled, “Population Genomic Screening of All Young Adults in a Healthcare System: A Cost Effectiveness Analysis.” That study concluded, “Preventive genomic screening in early adulthood would be highly cost-effective in a single-payer healthcare system, but ethical issues must be considered.” (Photo copyright: Monash University.)
Similar Genetic Studies Show Encouraging Results
Although the DNACancerScreen study in Australia is important, it is not the first to consider the impact of population-level screening for Tier 1 genetic mutations. The Healthy Nevada Project (HVN), a project that combined genetic, clinical, environmental, and social data, tested participants for those Tier 1 conditions. The project was launched in 2016 and currently has more than 50,000 participants, a Desert Research Institute (DRI) press release noted.
In 2018, HVN began informing participants who had increased risk for hereditary breast and ovarian cancer, Lynch Syndrome, and a third condition called Familial Hypercholesterolemia. There were 27,000 participants, and 90% of those who had genetic mutations associated with the three Tier 1 conditions had not been previously identified.
“Our first goal was to deliver actionable health data back to the participants of the study and understand whether or not broad population screening of CDC Tier 1 genomic conditions was a practical tool to identify at-risk individuals,” said Joseph Grzymski, PhD, lead author of the HVN study in the DRI press release.
Grzymski is Principal Investigator of the Healthy Nevada Project, Director of the Renown Institute for Health Innovation, Chief Scientific Officer for Renown Health, and a Research Professor in Computational Biology and Genetics at the Desert Research Institute.
“Now, two years into doing that it is clear that the clinical guidelines for detecting risk in individuals are too narrow and miss too many at risk individuals,” he added.
A total of 358, or 1.33% of the 26,906 participants in the Healthy Nevada Project were carriers for the Tier 1 conditions, but only 25% of them met the current guidelines for screening, and only 22 had any previous suspicion in their medical records of their genetic conditions.
Another project, the MyCode Community Health Initiative conducted at Geisinger Health System, found that 87% of participants with a Tier 1 gene variant did not have a prior diagnosis of a related condition. When the participants were notified of their increased risk, 70% chose to have a related, suggested procedure.
“This evidence suggests that genomic screening programs are an effective way to identify individuals who could benefit from early intervention and risk management—but [who] have not yet been diagnosed—and encourage these individuals to take measures to reduce their risk,” a Geisinger Health press release noted.
Realizing the Promise of Precision Medicine
Studies like these are an important step in realizing the potential of precision medicine in practical terms. The Tier 1 genetic conditions are just a few of the more than 22,000 recognized human genes of which scientists have a clear understanding. Focusing only on those few genetic conditions enables clinicians to better help patients decide how to manage their risk.
“Genomic screening can identify at-risk individuals more comprehensively than previous methods and start people on the path to managing that risk. The next step is figuring out the impact genomic screening has on improving population health,” said Adam Buchanan, MPH, MS, Director of Geisinger’s Genomic Medicine Institute.
These are positive developments for clinical laboratories and anatomic pathology group practices. The three examples cited above show that a proactive screening program using genetic tests can identify individuals at higher risk for certain cancers. Funding such programs will be the challenge.
At the current cost of genetic testing, screening 100 people to identify a few individuals at high risk for cancer would probably not be considered the highest and best use of the limited funds available to the healthcare system.
