Some patients with a genetic predisposition for cancer may not qualify for genetic screenings under the current guidelines, according to a recent study published by Samadder et al in JCO Precision Oncology. Researchers are investigating how to advance personalized medicine and tailor prevention and treatment strategies for these patients.
Background
Hereditary breast and ovarian cancer syndrome is linked to BRCA1 and BRCA2 mutations. Prior research has shown that BRCA1 mutations can lead to a 60% and 40% lifetime risk of developing breast cancer and ovarian cancers, respectively, among other cancers. BRCA2 mutations can increase the risk of developing breast and ovarian cancers to a respective 50% and 20%, with additional risks for prostate and pancreatic cancers in male patients. Lynch syndrome is associated with an 80% lifetime risk of developing colorectal cancer and a 50% risk of endometrial cancer.
Current screening protocols are often inadequate at detecting many patients who have genetic mutations associated with hereditary breast and ovarian cancer syndrome and Lynch syndrome—which increase the risk of developing certain types of cancers. This disparity may be particularly pronounced among underrepresented minorities.
“Early detection of genetic markers for these conditions can lead to proactive screenings and targeted therapies, potentially saving lives of [patients] and their family members,” explained lead study author Niloy Jewel Samadder, MD, a gastroenterologist and cancer geneticist at the Center for Individualized Medicine and the Comprehensive Cancer Center at the Mayo Clinic.
Study Methods and Results
In the Mayo Clinic Center for Individualized Medicine Tapestry project, researchers recruited 44,306 patients from diverse backgrounds to undergo genetic screenings. They sequenced patients’ exomes to identify disease-causing genetic mutations.
Among the patients, 1.24% (n = 550) were found to carry hereditary genetic mutations. Of note, 50% of the patients with genetic mutations were previously unaware of their hereditary genetic risk, and 40% of them did not meet existing clinical guidelines for genetic testing. The researchers also demonstrated disparities in how underrepresented minority patients met genetic screening guidelines compared with other patient groups.
Conclusions
The researchers revealed that the Tapestry project has sequenced the exomes of more than 100,000 patients and is integrating the results into the patients’ electronic health records to better personalize patient care and provide a data set for further genetic research. They noted that the overarching mission of the project is to advance personalized medicine and tailor prevention and treatment strategies for patients, thereby paving the way for targeted health-care interventions.
“This study is a wake-up call, showing us that current national guidelines for genetic screenings are missing too many [patients] at high risk of cancer,” stressed Dr. Samadder. “These results suggest the existing guidelines for genetic testing inadvertently introduce biases that affect who qualifies for testing and who receives coverage through health insurance. This leads to disparities in cancer prevention. Our [findings] emphasize the importance of expanding genetic screening to identify [patients] at risk for these cancer predisposition syndromes,” he concluded.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
