July 26, 2023

International workgroup of geneticists issues CHEK2 guidelines

International workgroup issues additional guidance on how to manage patients who carry inherited CHEK2 gene mutations that put them at a higher risk for cancer.

Clinicians now have additional guidance on how to manage patients who carry inherited CHEK2 gene mutations that put them at a higher risk for cancer.

The guidance was published Tuesday in Genetics in Medicine, the journal of the American College of Medical Genetics and Genomics. Inherited CHEK2 mutations have been linked to raised risks of breast cancer, colorectal cancer, and prostate cancer. But CHEK2 is largely considered a moderate risk gene, unlike the BRCA1 and BRCA2 mutations, which put people at much higher risk for cancers. Consequently, CHEK2 mutations have received less public attention than BRCA mutations.

Tuya Pal, associate professor of medicine and Ingram Associate Professor of Cancer Research (Daniel Dubois/Vanderbilt)
Tuya Pal, MD

Managing patients with CHEK2 mutations requires a more nuanced approach, said Tuya Pal, MD, associate director of Cancer Health Disparities at Vanderbilt-Ingram Cancer Center and Ingram Professor of Cancer Research, who served on the international workgroup that issued the CHEK2 guidance.

“CHEK2 mutations are common in individuals of European ancestry, and we must take the type of CHEK2 gene mutation as well as the personal and family history into account, when giving individuals with mutations guidance about their care,” said Pal.

The practice resource by the American College of Medical Genetics and Genomics, published Tuesday in the organization’s official journal, states that clinicians should consider multiple factors. While CHEK2 has largely been considered a moderate risk for breast cancer, the distinction is blurred with risk being on a continuum, ranging from low to moderate to high risk. The guidance states that the association of cancer risk with CHEK2 variants is complex and influenced by the specific variant, family history, non-CHEK2 genetic background and other factors. Consequently, personalized rather than generalized risk assessments are recommended by a clinician with expertise in cancer genetics and genetic counseling.

The president of the American College of Medical Genetics and Genomics and also a member of the international workgroup, Susan Klugman, MD, said the CHEK2 Clinical Practice Resource published Tuesday will provide more clarity for clinicians.

“This is an important resource for this moderate risk cancer predisposition gene and discusses risk influencers including family history, specific variant and genetic and nongenetic factors,” Klugman said. “This resource will clearly have a worldwide impact for those taking care of cancer patients and patients who are predisposed to cancer because of their CHEK2 variant status.”

The workgroup of geneticists who issued the recommendations performed a comprehensive review of literature in peer-reviewed journals before issuing the guidance. The group also identified knowledge gaps that researchers should address.

“In developing this resource, we sought to make practical guidance based on current high-quality, peer reviewed evidence and input from an international team of specialists in cancer genetics to help guide clinical practice in this complex area,” said the lead author of the guidance, Helen Hanson, MD, of the Southwest Thames Regional Genetics Service, St George’s University Hospitals National Health Service Foundation Trust, London, United Kingdom.