60 Germline Platelet Polygenic Risk Score Predicts Renal Cell Carcinoma Survival via Sustained Thrombocytosis

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A germline polygenic risk score for higher platelet counts predicts worse overall survival in renal cell carcinoma, an effect that operates predominantly through the sustained elevation of circulating platelets. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

Mustafa Saleh; Eddy Saad; Pablo Barrios; Wassim Daoud Khatoun; Jad El Masri; Marc Machaalani; Liliana Ascione; Clara Steiner; Rashad Nawfal; Razane El Hajj Chehade; Marc Eid; Élio Ibrahim; Gaelle Nafeh; Shaye Carver; Zeyun Lu; Emre Yekeduz; Tarek Baroud; Sara Sarrout; Ali Hajj Ali; Sylvan Baca; Alexander Gusev; Toni Choueiri

doi:10.1093/oncolo/oyag312.061

Key Points

To evaluate whether germline polygenic risk scores for hematologic measures associate with overall survival in patients with renal cell carcinoma.
Analyzed 495 patients with renal cell carcinoma who underwent tumor sequencing, imputing 321 hematological polygenic risk scores from the PGS Catalog.
Evaluated overall survival using left-truncated Cox proportional hazards regression models adjusted for technical covariates across diagnosis, sequencing, and immune checkpoint inhibitor initiation timepoints.
A polygenic risk score for higher platelet counts was significantly associated with worse survival (HR 1.37, 95% CI: 1.17–1.62, q = 0.027), whereas a score for elevated red cell distribution width was protective (HR 0.74, 95% CI: 0.63–0.87, q = 0.027).
Adjusting for longitudinal platelet counts attenuated the genetic score's association by 51%, while circulating platelet levels remained strongly adverse (HR 1.40, 95% CI: 1.29–1.58, p = 1.1x10⁻¹¹).
Pan-cancer analysis across 17 cancer types demonstrated that the platelet risk score's prognostic effect during immune checkpoint blockade was restricted exclusively to renal cell carcinoma.

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Implication

Cohort study reveals inherited high platelet risk scores reduce overall survival in renal cell carcinoma, indicating genetic drivers of thrombocytosis worsen cancer prognosis.

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Saleh et al. (2026) studied this question.

synapsesocial.com/papers/6a993626636c6408cfa7f0d0 https://doi.org/10.1093/oncolo/oyag312.061

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60 Germline Platelet Polygenic Risk Score Predicts Renal Cell Carcinoma Survival via Sustained Thrombocytosis

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60 Germline Platelet Polygenic Risk Score Predicts Renal Cell Carcinoma Survival via Sustained Thrombocytosis

Key Points

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Implication

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Cite This Study

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