Lag Times between Lymphoproliferative Disorder and Clinical Diagnosis of Chronic Lymphocytic Leukemia: A Prospective Analysis Using Plasma Soluble CD23
Year: 2014
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Chronic lymphocytic leukemia (CLL) is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time. METHODS: Within the European Prospective Investigation into Cancer cohort, we measured prediagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer. RESULTS: In a very large proportion of CLL patients' plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% confidence interval (CI), 0.90-1.00] for CLL diagnosed within 0.1 to 2.7 years after blood measurement, 0.90 (95% CI, 0.86-0.95) for diagnosis within 2.8 to 7.3 years, and 0.76 (95% CI, 0.65-0.86) for CLL diagnosed between 7.4 and 12.5 years. Even at a 7.4-year and longer time interval, elevated plasma sCD23 could predict a later clinical diagnosis of CLL with 100% specificity at >45% sensitivity. CONCLUSIONS: Our findings provide unique documentation for the very long latency times during which measurable B-cell lymphoproliferative disorder exists before the clinical manifestation of CLL. IMPACT: Our findings have relevance for the interpretation of prospective epidemiologic studies on the causes of CLL in terms of reverse causation bias. The lag times indicate a time frame within which an early detection of CLL would be theoretically possible. Cancer Epidemiol Biomarkers Prev; 24(3); 538-45. ©2014 AACR.
Authors: Rudolf Kaaks, Disorn Sookthai, Anna Łuczyńska, Christopher C. Oakes, Susen Becker, Theron Johnson, Annsofie Johansson, Beatrice Melin, Klas Sjöberg, Dimitrios Trichopoulos, Antonia Trichopoulou, Pagona Lagiou, Amalia Mattiello, Rosario Tumino, Giovanna Masala, Claudia Agnoli, Heiner Boeing, Krasimira Aleksandrova, Paul Brennan, Silvia Franceschi, Sandrine Roulland, Delphine Casabonne, Silvia de Sanjose, María-José Sánchez, José María Huerta, Eva Ardanaz, Nuria Sala, Kim Overvad, Anne Tjønneland, Jytte Halkjær, Elisabete Weiderpass, H. B(as). Bueno-de-Mesquita, Roel Vermeulen, Petra H. Peeters, Paolo Vineis, Rachel S. Kelly, Kay-Tee Khaw, Ruth C. Travis, Timothy J. Key, Elio Riboli, Alexandra Nieters
Institutions: German Cancer Research Center, University of Freiburg, University Medical Center Freiburg, Leipzig University, Umeå University, Lund University, Skåne University Hospital, Harvard University, Academy of Athens, Hellenic Health Foundation, National and Kapodistrian University of Athens, Federico II University Hospital, University of Naples Federico II, Istituto per lo Studio e la Prevenzione Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori, German Institute of Human Nutrition, Centre international de recherche sur le cancer, Aix-Marseille Université, Centre d’Immunologie de Marseille-Luminy, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Instituto de Investigación Biosanitaria de Granada, Andalusian School of Public Health, Instituto de Salud Pública de Navarra, Aarhus University, Danish Cancer Society, Karolinska Institutet, Cancer Registry of Norway, Folkhälsans Forskningscentrum, UiT The Arctic University of Norway, University Medical Center Utrecht, National Institute for Public Health and the Environment, Imperial College London, Utrecht University, Italian institute for Genomic Medicine, University of Cambridge, University of Oxford
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: World Health Organization, Deutsches Krebsforschungszentrum, Wellcome Trust, World Cancer Research Fund International, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, European Commission, Bundesministerium für Bildung und Forschung, Cancerfonden, Stavros Niarchos Foundation, NordForsk, Associazione Italiana per la Ricerca sul Cancro, Deutsche Krebshilfe, Hellenic Health Foundation, Medical Research Council, World Cancer Research Fund, Instituto de Salud Carlos III
OpenAlex ID: W2129098442