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Clin Cancer Res. 2018 Nov 15;24(22):5594-5601. doi: 10.1158/1078-0432.CCR-18-1496. Epub 2018 Jul 23.

KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer: A Prospective Nested Case-Control Study.

Author information

1
International Agency for Research on Cancer (IARC), Lyon, France.
2
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom. david.muller@imperial.ac.uk rbhatt@bidmc.harvard.edu.
3
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
4
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
5
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
6
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands.
7
Institute for Risk Assessment Sciences, Utrecht University, the Netherlands.
8
Department of Public Health, Section for Epidemiology, Aarhus University, Denmark.
9
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
10
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands.
11
Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
12
CESP, Faculté de Médecine, Université Paris-Sud, Faculté de médecine, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.
13
Gustave Roussy, Villejuif, France.
14
Laboratoire de Mathématiques Appliquées MAP5 (UMR CNRS 8145), Université Paris Descartes, Paris, France.
15
Hellenic Health Foundation, Athens, Greece.
16
Department of Clinical Sciences and Community Health Università degli Studi di Milano, Milan, Italy.
17
2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari, Greece.
18
Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute, ISPO, Florence, Italy.
19
Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
20
Dipartimento Di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
21
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
22
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
23
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
24
Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
25
Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Institut Catatlà d'Oncologia, L'Hospitalet de Llobregat, Spain.
26
Public Health Directorate, Asturias, Spain.
27
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
28
CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
29
Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
30
Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
31
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford.
32
Department of Medicine, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
33
Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, Massachusetts.
34
Department of Medicine, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. david.muller@imperial.ac.uk rbhatt@bidmc.harvard.edu.
#
Contributed equally

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 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 = 4.1 × 10-23], 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 = 0.0053).Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival. Clin Cancer Res; 24(22); 5594-601. ©2018 AACR.

PMID:
30037816
PMCID:
PMC6239904
[Available on 2019-05-15]
DOI:
10.1158/1078-0432.CCR-18-1496

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