Abstract Purpose: Historically, indigent populations have faced significant disparities in access to germline testing for various gastrointestinal (GI) cancers. With the rising incidence of GI cancers among adults under 50, coupled with evidence that pathogenic germline variants (PGVs) in young-onset (YO) cancers can be present in over 20% of cases, there is a critical need to address barriers to genetic testing in underserved populations. This study aimed to assess the feasibility and impact of a multilevel intervention designed to optimize the implementation of universal germline testing (UGT) in a county hospital system serving a predominantly low-income population. Methods: Between March 2024 and September 2025, patients aged 50 years and younger, diagnosed with GI cancers, and receiving care at Lyndon B. Johnson Hospital in Houston, Texas, were recruited for the study. Participants were universally offered germline testing with a 48-gene multiplex panel covering major hereditary cancer predisposition syndromes, along with pre-recorded video education and standardized pretest counseling. Pre- and post-test surveys were administered to assess patient-level impacts on genetic knowledge, psychosocial factors, and stressors related to UGT. The primary outcomes included the proportion of patients with YO GI cancers who completed germline testing, compared to historical controls (previously reported completion rate: 49%), and the feasibility of implementing this universal approach. Results: Of the 64 eligible patients, 41 (64%) enrolled in the pilot study and completed germline testing. The majority of participants had colorectal cancer (48%), followed by gastro-esophageal cancers (12%). The median age at diagnosis was 42 years (range: 24-50). Spanish was the primary language spoken by 68% of participants, and 40% were diagnosed with stage IV cancer. Pathogenic germline variants (PGVs) were identified in 16% of participants, while variants of uncertain significance (VUS) were found in 42%. PGVs included BRCA2, FAP, MLH1, and ATM. Patient level impacts of the intervention on genetic knowledge, psychosocial factors, and stressors related to UGT will be reported. Conclusion: The rate of PGVs among this underserved population was notably high, with approximately 1 in 6 patients diagnosed with GI cancers at or under the age of 50 carrying a germline mutation linked to cancer. The universal approach to germline testing proved to be feasible and resulted in a higher completion rate compared to historical controls, who were offered targeted testing. This pilot demonstrates strong interest in UGT among underserved cancer patients and suggests that improving the framework for genetic testing in this context is a valuable investment for enhancing clinical outcomes and equitable access to genetic insights. Citation Format: Kaysia Ludford, Ysaith Orellana Ascencio, Hilary Ma, Yi-Qian Nancy You. Universal Germline Testing in Young-Onset GI Malignancies: Expanding Access for Underserved Patients abstract. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31 (23Suppl): Abstract nr B025.
Ludford et al. (Wed,) studied this question.