CA19-9 and Apolipoprotein-A2 isoforms as detection markers for pancreatic cancer - a prospective evaluation

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  • K Honda, Japan Agency for Medical Research and Development (AMED)-Core Research for Evolutionary Medical Science and Technology (CREST), Japan Agency for Medical Research and Development, 100-0004 Tokyo, Japan., Japan
  • V A Katzke, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Tyskland
  • A Hüsing, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Tyskland
  • S Okaya, Department of Biomarker for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan., Japan
  • H Shoji, Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan., Japan
  • K Onidani, Department of Biomarker for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan., Japan
  • A Olsen
  • A Tjønneland, Research Diet, Genes and Environment Danish Cancer Society Research Center Strandboulevarden, Copenhagen, Denmark., Danmark
  • Kim Overvad
  • E Weiderpass, Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland., Finland
  • P Vineis, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, W2 1NY London, UK., Storbritannien
  • D Muller, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, W2 1NY London, UK., Storbritannien
  • K K Tsilidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece, Grækenland
  • D Palli, Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, 50139 Florence, Italy., Italien
  • V Pala, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy., Italien
  • R Tumino, Cancer Registry and Histopathology Unit, 'Civic-M.P. Arezzo' Hospital, 97100 ASP Ragusa, Italy., Italien
  • A Naccarati, Italian Institute for Genomic Medicine (IIGM/HuGeF), Torino, Italy., Italien
  • S Panico, Dipartimento di Medicina Clinica e Chirurgia, Federico II University, 80138 Naples, Italy. spanico@unina.it., Italien
  • K Aleksandrova, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, 14558, Germany., Tyskland
  • H Boeing, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, 14558, Germany., Tyskland
  • H B Bueno-de-Mesquita, Academic Icon / visiting professor, Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, 50603, Kuala Lumpur, Malaysia., Malaysia
  • P H Peeters, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK., Storbritannien
  • A Trichopoulou, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 157 72 Athens, Greece. atrichopoulou@hhf-greece.gr., Grækenland
  • P Lagiou, Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA., USA
  • K-T Khaw, Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK., Storbritannien
  • N J Wareham, MRC Epidemiology Unit, University of Cambridge, Cambridge, UK., Storbritannien
  • R C Travis, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Storbritannien
  • S Merino, Public Health Directorate, Asturias, Spain, Acknowledgment of funds: Regional Government of Asturias., Spanien
  • E J Duell, Scientific Coordinator, PanC4 Consortium, Unit of Nutrition and Cancer | Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Spanien
  • M Rodríguez-Barranco, Consortium for Biomedical Research in Epidemiology and Public Health (CIBER- CIBERESP), 28029 Madrid, Spain., Spanien
  • M D Chirlaque, Murcia Regional Health Council, CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Ronda de Levante, 11. E30008 Murcia, Spain., Spanien
  • A Barricarte, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain., Spanien
  • V Rebours, INSERM - UMR 1149, University Paris 7, France., Frankrig
  • M-C Boutron-Ruault, Institut Gustave Roussy, Villejuif, France., Frankrig
  • F Romana Mancini, CESP, INSERM U1018, Univ. Paris-Sud, UVSQ, Université Paris-Saclay, Villejuif Cedex, France., Frankrig
  • P Brennan, Section of Genetics, International Agency for Research on Cancer (IARC), World Health Organization, 150 cours Albert Thomas, Lyon, France., Frankrig
  • G Scelo, Section of Genetics, International Agency for Research on Cancer (IARC), World Health Organization, 150 cours Albert Thomas, Lyon, France., Frankrig
  • J Manjer, Department of Surgery, Lund University, Skåne University Hospital, Malmö, Sweden, Sverige
  • M Sund, Department of Surgical and Preoperative Sciences, Umeå University, Sweden., Sverige
  • D Öhlund, Department of Radiation Sciences and Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden., Sverige
  • F Canzian, Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Tyskland
  • R Kaaks, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Tyskland

Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. This study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
TidsskriftInternational Journal of Cancer
Vol/bind144
Nummer8
Sider (fra-til)1877-1887
Antal sider11
ISSN0020-7136
DOI
StatusUdgivet - 2019

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