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Int J Cancer. 2018 Apr 1;142(7):1355-1360. doi: 10.1002/ijc.31164. Epub 2017 Dec 11.

Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort.

Author information

1
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Ob/Gyn Epidemiology Center, Brigham and Women's Hospital, Boston, MA.
3
Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA.
4
Laboratory of Genital Tract Biology, Brigham and Women's Hospital, Boston, MA.
5
Unit of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
6
Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
7
INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, F-94805, France.
8
Université Paris Sud, UMRS 1018, Villejuif, F-94805, France.
9
Gustave Roussy, Villejuif, F-94805, France.
10
Human Genetics Foundation (HuGeF), Torino, Italy.
11
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
12
Hellenic Health Foundation, Athens, Greece.
13
Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, WHO Collaborating Center for Nutrition and Health, National and Kapodistrian University of Athens, Athens, Greece.
14
Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
15
Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
16
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
17
Cancer Registry and Histopathology Unit, "Civic-M.P-Arezzo" Hospital, ASP Ragusa, Italy.
18
Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
19
Dipartimeno di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
20
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
21
MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
22
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
23
Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
24
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
25
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
26
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
27
Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
28
Public Health Directorate, Asturias, Spain.
29
Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.
30
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
31
CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
32
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
33
Navarra Public Health Institute, Pamplona, Spain.
34
IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
35
Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Donostia, Spain.
36
Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
37
Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
38
Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.
39
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
40
Cancer Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
41
Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, Oxford, United Kingdom.
42
International Agency for Research on Cancer, Lyon, France.
43
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom.

Abstract

CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; phet  = 0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection.

KEYWORDS:

CA125; MUC16; anti-CA125 antibodies; autoantibodies; early detection markers; ovarian cancer

PMID:
29159934
PMCID:
PMC5805613
DOI:
10.1002/ijc.31164
[Indexed for MEDLINE]
Free PMC Article

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