Mustafa Saleh, MD, discusses germline platelet polygenic risk score for renal cell carcinoma

In an interview at the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California, Mustafa J. Saleh, MD, discussed findings from a study examining whether germline-derived polygenic risk scores could help predict outcomes for patients with kidney cancer. Saleh is a research fellow at Dana-Farber Cancer Institute in Boston, Massachusetts.

The analysis included 495 patients with kidney cancer who were treated at Dana-Farber Cancer Institute and had tumor sequencing performed using targeted oncology panels. Investigators used an imputation pipeline to derive germline genetic information and calculated more than 300 polygenic risk scores related to complete blood count traits. Among these, 2 scores were significantly associated with overall survival after correcting for multiple testing. Notably, a polygenic risk score related to platelet levels showed that patients with higher scores had a 37% greater risk of death (HR, 1.37, CI, 1.17 to 1.62; q = 0.027), suggesting that inherited genetic variation influencing platelet biology may affect survival outcomes in kidney cancer.

Further analyses helped clarify the mechanism behind this association. When investigators adjusted for measured platelet levels, the survival association disappeared, indicating that the genetic risk score likely operates through platelet-related biological pathways rather than an independent mechanism. The team also evaluated whether this association appeared in other cancer types and found that it was unique to kidney cancer, highlighting a potential disease-specific interaction between platelet biology and tumor behavior.

According to Saleh, these findings suggest that germline genetic information related to platelet biology may represent a novel prognostic signal in kidney cancer. Because current prognostic models such as the IMDC risk model rely on clinical factors measured after diagnosis, integrating germline genetic information could eventually add a new layer of risk stratification and improve understanding of the tumor microenvironment and immune interactions that influence response to therapy.

REFERENCE

1. Saleh M, Saad E, Barrios P, et al. Germline platelet polygenic risk score to predict renal cell carcinoma survival via sustained thrombocytosis. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract 543. https://www.asco.org/abstracts-presentations/256737/abstract