Outcomes of 'in-house' genetic testing within a specialist hereditary colorectal cancer registry

Approximately 5%-10% of colorectal cancer (CRC) cases are due to known Mendelian syndromes. This study aimed to report the diagnostic yield of constitutional genetic testing, alongside clinicopathological factors for hereditary CRC, within a specialised National Bowel Hospital, and outside traditional genetics referral pathways.

This study retrospectively reviewed clinical, pathological and genetic factors using prospectively collected data from the St Mark's Hospital Centre for Familial Intestinal Cancer registry. Between December 2021 and June 2023, consecutive patients at risk of hereditary CRC were selected for genetic testing according to UK National Genomic Testing criteria. The diagnostic yield of genetic testing was calculated by indication. Statistical analysis for clinicopathological data was performed using the Mann-Whitney U test, chi-square test and logistic regression.

A total of 283 consecutive patients underwent genetic testing, 100 (35.3%) mainstreamed with CRC, 95 (33.6%) with multiple polyps, 74 (26.6%) had cascade testing (within families where the probands were known to the registry) and other testing including 'unaffected' patients with a relevant family history. Variants were detected in 85 of 283 (30%) patients with known CRC predisposition genes. Diagnostic yields were high for deficient mismatch repair (dMMR) cancer with Lynch syndrome (LS) at 45%, and also for multiple adenoma cohorts at 16%; and in CRC patients under 40 years (irrespective of tumour MMR status) at 16%.

Genetic testing performed by our specialist unit provides patients with a high-yield, and effective genetic diagnosis, directly indicating comprehensive lifelong care, outside the context of a traditional genetics service.