Genetic Risk Evaluation for Patients Younger Than 46 Years With RCC

A new study presented by Dr. Lan Chen at the 24th Annual Meeting of the Society of Urologic Oncology reviewed the benefits of genetic risk evaluation for patients with renal cell carcinoma (RCC) who are 46 years or younger.

The National Comprehensive Cancer Network recommends that patients 46 years or younger undergo genetic risk evaluation upon receiving an RCC diagnosis.

Researchers noted the importance of determining if a patient has hereditary RCC caused by a germline pathogenic variant in a renal cancer risk gene. Identifying hereditary RCC can assist physicians in prescribing correct care, such as clinical management and genetic counseling.

Dr. Chen and colleagues sought to identify the frequency of germline mutations in patients 46 years or younger. They evaluated the whole exome sequencing data for 21 genes with mutations connected to increased odds of an RCC diagnosis in 60 patients younger than 46 years included in the Penn Medicine BioBank.

After identifying 4223 variants in the participating patients, the study discovered 6 pathogenic or likely pathogenic variants. Each of the 6 variants was found in 1 individual. Four pathogenic variants were found in the VHL gene, 1 was found in the CHEK2 gene, and 1 was found in the PMS2 gene.

Three patients with a pathogenic variant in the VHL gene had undergone diagnostic clinical testing prior, while 1 patient underwent no prior testing and reported a family history of RCC connected with Von Hippel-Lindau syndrome. Two patients were found to have pathogenic variants that were unidentified by clinical testing.

Researchers concluded that the standard of offering genetic testing using age at diagnosis should be reconsidered because of the low diagnosis yield of identifying patients with an unknown pathogenic or likely pathogenic variant using age alone.

“The identification of an inherited P/LP variant in renal cancer susceptibility genes can facilitate prevention strategies for RCC, including, but not limited to, cancer surveillance, genetic testing of family members, and education and awareness of non-RCC tumor risks,” the researchers wrote.