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Clinical Research and Public HealthIn-Press PreviewNephrologyOncology Open Access | 10.1172/jci.insight.198098

Pan-cancer polygenic risk score associates with cancer susceptibility following kidney transplantation

Jarmo Ritari,1 Kati Hyvärinen,1 Kirsi Jahnukainen,2 Jukka Partanen,1 Ilkka Helanterä,3 and Timo Jahnukainen4

1Finnish Red Cross Blood Service, Helsinki, Finland

2Division of Hematology-Oncology and Stem Cell Transplantation, University of Helsinki, Helsinki, Finland

3Transplantation and Liver Surgery, University of Helsinki, Helsinki, Finland

4Department of Pediatric Nephrology and Transplantation, University of Helsinki, Helsinki, Finland

Find articles by Ritari, J. in: PubMed | Google Scholar

1Finnish Red Cross Blood Service, Helsinki, Finland

2Division of Hematology-Oncology and Stem Cell Transplantation, University of Helsinki, Helsinki, Finland

3Transplantation and Liver Surgery, University of Helsinki, Helsinki, Finland

4Department of Pediatric Nephrology and Transplantation, University of Helsinki, Helsinki, Finland

Find articles by Hyvärinen, K. in: PubMed | Google Scholar

1Finnish Red Cross Blood Service, Helsinki, Finland

2Division of Hematology-Oncology and Stem Cell Transplantation, University of Helsinki, Helsinki, Finland

3Transplantation and Liver Surgery, University of Helsinki, Helsinki, Finland

4Department of Pediatric Nephrology and Transplantation, University of Helsinki, Helsinki, Finland

Find articles by Jahnukainen, K. in: PubMed | Google Scholar

1Finnish Red Cross Blood Service, Helsinki, Finland

2Division of Hematology-Oncology and Stem Cell Transplantation, University of Helsinki, Helsinki, Finland

3Transplantation and Liver Surgery, University of Helsinki, Helsinki, Finland

4Department of Pediatric Nephrology and Transplantation, University of Helsinki, Helsinki, Finland

Find articles by Partanen, J. in: PubMed | Google Scholar

1Finnish Red Cross Blood Service, Helsinki, Finland

2Division of Hematology-Oncology and Stem Cell Transplantation, University of Helsinki, Helsinki, Finland

3Transplantation and Liver Surgery, University of Helsinki, Helsinki, Finland

4Department of Pediatric Nephrology and Transplantation, University of Helsinki, Helsinki, Finland

Find articles by Helanterä, I. in: PubMed | Google Scholar

1Finnish Red Cross Blood Service, Helsinki, Finland

2Division of Hematology-Oncology and Stem Cell Transplantation, University of Helsinki, Helsinki, Finland

3Transplantation and Liver Surgery, University of Helsinki, Helsinki, Finland

4Department of Pediatric Nephrology and Transplantation, University of Helsinki, Helsinki, Finland

Find articles by Jahnukainen, T. in: PubMed | Google Scholar

Published April 23, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.198098.
Copyright © 2026, Ritari et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 23, 2026 - Version history
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Abstract

Background Cancer accounts for over 20% of late post-transplant mortality, yet the contribution of genetic susceptibility to post-transplant cancer risk remains unclear. This study investigates germline genetic risk factors for post-transplant cancer in the Finnish population using data from the FinnGen cohort. Methods A pan-cancer polygenic risk score (PRS) was constructed using genetic variants identified in UK and US populations to assess the influence of common germline variants on time to first cancer diagnosis in 1,802 Finnish kidney transplant recipients (KTRs), of whom 317 developed post-transplant cancer. The PRS was first validated in the FinnGen non-transplantation cohort and subsequently applied to KTRs, with replication in lung and liver transplant recipients (n = 476). Functional relevance was explored by assessing associations between the PRS and expression levels of 2,923 plasma proteins in the UK Biobank (n = 53,013). Results Compared to a matched non-transplantation cohort (n = 68,294), KTRs exhibited earlier cancer onset. The PRS was significantly associated with time to first cancer diagnosis in the non-transplantation population (HR 1.04; 95% CI 1.038-1.056; p = 3.75 x 10-25). Among KTRs younger than 40 years, higher PRS was associated with earlier cancer onset (HR, 1.08; 95% CI ,1.01-1.17; p = 0.036), indicating a stronger genetic effect at younger ages. The PRS significantly (Bonferroni < 0.05) altered the regulation of 87 plasma proteins, several of which were known cancer-related markers. Conclusion Inherited genetic predisposition, captured by pan-cancer PRS, may contribute to individual susceptibility to cancer after solid organ transplantation, particularly at younger ages.

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