A recent Mayo Clinic study published in JCO Precision Oncology reveals that current clinical genetic screening guidelines may be insufficient in identifying individuals at risk for hereditary breast-ovarian cancer syndromes and Lynch syndrome. The research, which involved exome sequencing of over 44,000 participants, found that a significant number of individuals carrying hereditary mutations were unaware of their genetic predisposition to these diseases, highlighting the need for expanded screening approaches.
The study identified 550 individuals (1.24%) as carriers of hereditary mutations associated with breast and ovarian cancer (BRCA1, BRCA2) and Lynch syndrome (MSH6, PMS2, MLH1, MSH2, EPCAM). Strikingly, half of these carriers were previously unaware of their genetic risk, and 40% did not meet the genetic testing guidelines established by the National Comprehensive Cancer Network (NCCN).
Key Findings and Implications
The research underscores the limitations of current screening guidelines, particularly for minorities, who were less likely to meet NCCN criteria compared to White participants (51.5% vs. 37.5%). The findings suggest that a more comprehensive approach to genetic screening, utilizing exome sequencing, could identify at-risk individuals who are currently being missed.
"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, gastroenterologist and cancer geneticist at Mayo Clinic’s Center for Individualized Medicine and Comprehensive Cancer Center.
Methodology and Collaboration
The study was conducted as part of the Mayo Clinic Center for Individualized Medicine Tapestry study, in collaboration with Helix, a population genomics company. Exome sequencing was performed on genes associated with hereditary breast and ovarian cancer and Lynch syndrome. The researchers analyzed data from participants recruited from Mayo Clinic sites in Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla.
Impact on Personalized Medicine
Mayo Clinic is integrating exome sequencing data into patients' electronic health records (EHRs) as part of the Tapestry project. This integration aims to provide clinicians with easy access to genomic information, facilitating informed decision-making and advancing genomically informed medicine.
"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.
The Future of Genetic Screening
As the cost of gene sequencing continues to decrease, the implementation of broader screening programs for cancer risk factors may become more economically feasible. This could lead to an expanded role for medical laboratories in utilizing exome and whole-genome sequencing to screen patients for various cancers and health conditions, ultimately improving early detection and personalized treatment strategies.
