Diagnostic yield of germline genetic testing for early-onset colorectal cancer in a safety-net healthcare system.

88 Background: Germline genetic testing (GGT) is recommended for all individuals with early-onset colorectal cancer (eoCRC), defined as diagnosis before age 50. The diagnostic yield of GGT in eoCRC patients has been reported to range from 16-25%, although these estimates are largely derived from studies in resource-rich settings with limited diversity of patient ancestry. The aim of this study was to characterize the results of GGT in a predominantly Hispanic cohort of patients with eoCRC evaluated in a safety-net healthcare system. Methods: Clinical data were retrospectively analyzed from patients referred to an adult genetics clinic in a safety-net healthcare system (Harris Health System in Houston, TX) from 2015-2024. Patients with a history of eoCRC who were 0.05 for all). 29.4% of all tested patients had at least one variant of uncertain significance in a cancer-associated gene. Conclusions: In this predominantly Hispanic cohort of patients treated in a safety-net healthcare system, the diagnostic yield of GGT for eoCRC was 22%. Over 40% of those with a positive result would not have met family history-based criteria for testing prior to CRC onset, supporting consideration of broader or even universal GGT of high-penetrance genes. Ensuring access to guideline-informed genetic testing, including in resource-limited settings, is essential to facilitate timely diagnosis of actionable genetic variants.