KIM-1 as a blood-based marker for early detection of kidney cancer: A prospective nested case–control study
Scelo, Ghislaine; Muller, David C.; Riboli, Elio; Johansson, Mattias; Cross, Amanda J.; Vineis, Paolo; Tsilidis, Konstantinos K.; Brennan, Paul; Boeing, Heiner; Peeters, Petra H.M.; Vermeulen, Roel C.H.; Overvad, Kim; Bas Bueno-de-Mesquita, H.; Severi, Gianluca; Perduca, Vittorio; Kvaskoff, Marina; Trichopoulou, Antonia; Vecchia, Carlo La; Karakatsani, Anna; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Weiderpass, Elisabete; Sandanger, Torkjel M.; Nøst, Therese H.; Agudo, Antonio; Ramon Quiros, J.; Rodríguez-Barranco, Miguel; Chirlaque, Maria Dolores; Key, Timothy J.; Khanna, Prateek; Bonventre, Joseph V.; Sabbisetti, Venkata S.; Bhatt, Rupal S.
(2018) Clinical Cancer Research, volume 24, issue 22, pp. 5594 - 5601
(Article)
Abstract
Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to
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clinical diagnosis. Experimental Design: KIM-1 concentrations were measured in prediagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to 5 years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival. Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 [95% confidence interval (CI), 1.44–2.03, P ¼ 4.1 1023], corresponding to an IRR of 63.3 (95% CI, 16.2–246.9) comparing the 80th to the 20th percentiles of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index, and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver-operating characteristic curve of 0.8 compared with 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (P ¼ 0.0053). Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival.
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Keywords: Oncology, Cancer Research
ISSN: 1078-0432
Publisher: American Association for Cancer Research Inc.
Note: Funding Information: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santéet de la Recherche Médicale (Inserm), (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare, and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Anda-lucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020; Spain); Swedish Cancer Society, Swedish Scientific Council and County Councils of Ska°ne and V€asterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford United Kingdom). Funding Information: The authors thank all participants in the EPIC cohort for their invaluable contribution to the study. R.S. Bhatt was funded by NIH R01 CA196996 and NIH P50 CA101942-12. D.C. Muller was funded by a Cancer Research UK Population Research Fellowship. Publisher Copyright: © 2018 American Association for Cancer Research.
(Peer reviewed)