Cascade genetic testing in Lynch syndrome families

Abstract

Introduction: Lynch syndrome (LS) is the most common form of inherited genetic predisposition to colorectal cancer (CRC). LS is caused by a germline pathogenic/likely pathogenic variant (P/ LPV) in one of the mismatch repairs (MMR). Since LS is linked to an increased risk of cancer, it is crucial to test both individuals and their family members (cascade testing). Methods: We performed the analysis of data from the Department of Clinical Cancer Genetics, the Institute of Oncology Ljubljana, i.e. the information on individuals suspected of LS who were referred for genetic counselling between 01/01/2007 and 31/12/2023. The research was conducted using descriptive statistical methods. Results: A total of 246 individuals from 97 LS-positive families were referred for genetic counselling in 17 years. 170 individuals tested positive, representing 69.1% of all individuals tested. 157 family members from 54 families (55.7%) participated in cascade testing. There were 100 women (63.7%) and 57 men (36.3%). In families where the relatives opted for cascade testing, 90 individuals (57.3%) responded within 12 months after the positive result had been disclosed to the first individual tested. On average, 1.6 blood relatives per family participated in presymptomatic testing. In 54 families where relatives opted for testing, the average number of those who decided to test was 2.9 relatives per family. Conclusion: Cascade genetic testing is a successful systematic method for providing genetic testing to blood relatives of P/LPV carriers. In the case of LS, 55.7% of positive families had at least one blood relative opting for cascade testing. In families where relatives underwent cascade testing, an average of nearly three relatives participated, with almost 60% responding within 12 months.

Keywords

• genetic testing
• cascade testing
• hereditary nonpolyposis colorectal cancer
• HNPCC
• Lynch syndrome
• blood relative