Abstract NG11: Understand germline determinants of cancer progression using multi-ancestral real-world data

Abstract Inherited genetic variation influences the evolutionary course of cancer, yet the contribution of common germline variants to tumor genomic architecture and patient outcomes is not well defined. While rare, high-penetrance mutations often promote tumorigenesis through secondary somatic hits in the same gene, the role of more prevalent, low-effect variants remains less clear. Genome-wide association studies have uncovered numerous common susceptibility loci, and emerging evidence suggests that some of these variants are associated with specific somatic driver events. However, a systematic understanding of how common germline variation shapes patterns of somatic mutation across pathways and influences tumor development is still lacking. Elucidating these germline-somatic interactions may reveal previously unrecognized mechanisms governing tumor initiation, clonal selection, and progression, ultimately providing new insights for cancer risk stratification and therapeutic intervention. Citation Format: Jian Carrot-Zhang. Understand germline determinants of cancer progression using multi-ancestral real-world data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr NG11.