Half of People at Risk of Hereditary Cancer Are Unaware of It

The Growing Importance of Hereditary Cancers

About 5-10% of all cancers are hereditary, although current research suggests that the proportion may be higher. Despite advances in genetic technology, many people at risk of hereditary cancer remain unaware of it. Research shows that current genetic screening guidelines fail to adequately identify patients with conditions such as hereditary breast and ovarian cancer syndrome and Lynch syndrome . These shortcomings result in missed opportunities for early diagnosis and intervention, reducing access to potentially lifesaving treatment for patients and their families.

Published on July 16, 2024, in JCO Precision Oncology , a study led by Niloy Jewel Samadder involving 44 thousand patients emphasizes the need to reconsider genetic screening guidelines. Making these screenings more inclusive could help save many lives.

50% of People at Risk of Hereditary Cancer Are Unaware of It: Gaps in Genetic Screening Guidelines

Some patients with genetic predispositions to cancer may not qualify for genetic screening under current guidelines. Researchers are exploring ways to advance personalized medicine and tailor prevention and treatment strategies for these patients.

Explanation of Terms:

• Hereditary Breast and Ovarian Cancer Syndrome: BRCA1 and BRCA2 mutations cause this genetic condition, which increases the risk of breast and ovarian cancers.
• Lynch Syndrome: A genetic syndrome that predisposes individuals to various cancers, particularly colorectal and endometrial cancers.
• Personalized Medicine: The use of treatment and prevention strategies tailored to a patient's genetic information.
• Genetic Screening: Tests performed to identify genetic diseases or risks.

Important Mutations

Hereditary breast and ovarian cancer syndrome is associated with BRCA1 and BRCA2 mutations. Previous research has shown that BRCA1 mutations increase the lifetime risk of developing breast cancer by 60% and ovarian cancer by 40%. BRCA2 mutations increase the risk of breast and ovarian cancers by 50% and 20%, respectively, and may also increase the risk of prostate and pancreatic cancers in men. Lynch syndrome has been associated with a lifetime colorectal cancer risk of 80% and an endometrial cancer risk of 50%.

Shortcomings of Current Guidelines

Current screening protocols fail to identify many patients carrying genetic mutations associated with hereditary breast and ovarian cancer syndrome and Lynch syndrome. This may be particularly pronounced among underrepresented minorities.

"Early detection of genetic markers for these conditions can save patients' and family members' lives through proactive screening and targeted treatments," explains the study's lead author, Dr. Niloy Jewel Samadder, a gastroenterologist and cancer geneticist at Mayo Clinic's Center for Individualized Medicine and Comprehensive Cancer Center.

Study Methods and Results

In the Mayo Clinic Center for Individualized Medicine's Tapestry project, researchers enrolled 44,306 patients from diverse backgrounds for genetic screening. They sequenced patients' exomes to identify disease-causing genetic mutations.

Note: Mayo Clinic's Tapestry project includes participants with a wide range of health conditions. The Tapestry study encompasses more than 100 thousand participants with diverse health statuses and genetic characteristics, including both healthy individuals and people genetically predisposed to various diseases.

• 1.24% of patients (550 individuals) were found to carry hereditary genetic mutations.
• Of the genetic mutations, 42.8% were found in BRCA2, 27.2% in BRCA1, 12.3% in MSH6, and 8.8% in PMS2, with 4.5% in MLH1 and 0.2% in EPCAM.
• 46.4% of participants had a personal history of cancer.
• Among carriers of hereditary breast and ovarian cancer syndrome, 35.1% had a history of breast cancer; among Lynch syndrome carriers, 26.1% had a history of colorectal cancer.
• Of all participants, 27.9% had a history of breast cancer and 10.7% a history of colorectal cancer.
• 50% of patients carrying genetic mutations had previously been unaware of their hereditary genetic risk, and 40% did not meet the criteria for genetic testing under current clinical guidelines.

Commentary

The 1.24% figure in the study indicates the proportion of the general population, including healthy individuals, at risk of hereditary cancer. This differs from the statement that 5-10% of all cancers are hereditary, because one refers to the general population and the other only to people diagnosed with cancer. This distinction emphasizes the importance of genetic screening to identify hereditary cancer risk in the general population and its potential to identify at-risk individuals even before a cancer diagnosis.

The researchers explained that the Tapestry project had sequenced the exomes of more than 100 thousand patients and integrated the results into their electronic health records to personalize patient care and provide a dataset for further genetic research. They stated that the project's overall mission was to advance personalized medicine and tailor prevention and treatment strategies for patients.

This study clearly demonstrates that current national genetic screening guidelines miss many patients at high risk of cancer. The results show that these guidelines may inadvertently introduce bias when determining who qualifies for testing and who is covered by health insurance. This creates inequalities in cancer prevention. The findings emphasize the importance of expanding genetic screening to identify at-risk patients with these cancer predisposition syndromes.