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Cancer Epidemiol Biomarkers Prev. 2018 Jul;27(7):790-804. doi: 10.1158/1055-9965.EPI-17-0744. Epub 2018 Apr 16.

Anti-CA15.3 and Anti-CA125 Antibodies and Ovarian Cancer Risk: Results from the EPIC Cohort.

Author information

1
Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts. dcramer@bwh.harvard.edu r.kaaks@dkfz.de.
2
Harvard Medical School, Boston, Massachusetts.
3
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
4
Laboratory of Genital Tract Biology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts.
5
Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts.
6
Navarra Public Health Institute, Pamplona, Spain.
7
IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
8
CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain.
9
School of Public Health, Imperial College London, London, United Kingdom.
10
German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
11
Department of Clinical Sciences, Lund University, Sweden.
12
Division of Surgery, Skåne University Hospital, Lund, Sweden.
13
CESP, INSERM U1018, Univ. Paris-Sud, UVSQ, Université Paris-Saclay, Villejuif, France.
14
Gustave Roussy, Villejuif, France.
15
Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
16
CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
17
Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
18
Public Health Direction and Biodonostia Research Institute and Ciberesp, Basque Regional Health Department, San Sebastian, Spain.
19
International Agency for Research on Cancer, Lyon, France.
20
Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.
21
Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
22
Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
23
Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
24
Division of Cancer Epidemiology, German Cancer Research Center, (DKFZ) Heidelberg, Germany.
25
School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
26
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
27
Diparmento di Medicina Clinica e Chirugria Federico II University, Naples, Italy.
28
Department of Medical Sciences, University of Torino, Italian Institute for Genomic Medicine -IIGM (FKA HuGeF), Torino, Italy.
29
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.
30
Hellenic Health Foundation, Athens, Greece.
31
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, Athens, Greece.
32
Julis Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
33
Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
34
Public Health Directorate, Asturias, Spain.
35
Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
36
CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
37
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
38
Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy.
39
Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
40
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
41
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
42
Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
43
Division of Cancer Epidemiology, German Cancer Research Center, (DKFZ) Heidelberg, Germany. dcramer@bwh.harvard.edu r.kaaks@dkfz.de.

Abstract

Background: Neoplastic and non-neoplastic events may raise levels of mucins, CA15.3, and CA125, and generate antibodies against them, but their impact on epithelial ovarian cancer (EOC) risk has not been fully defined.Methods: CA15.3, CA125, and IgG1 antibodies against them were measured in 806 women who developed EOC and 1,927 matched controls from the European Prospective Investigation of Nutrition and Cancer. Associations between epidemiologic factors and anti-mucin antibodies were evaluated using generalized linear models; EOC risks associated with anti-mucin antibodies, by themselves or in combination with respective antigens, were evaluated using conditional logistic regression.Results: In controls, lower antibodies against both mucins were associated with current smoking; and, in postmenopausal women, higher levels with longer oral contraceptive use and later-age-at and shorter-interval-since last birth. Lower anti-CA15.3 antibodies were associated with higher body mass and, in premenopausal women, more ovulatory cycles. Higher anti-CA15.3 and anti-CA125 antibodies were associated with higher risk for mucinous EOC occurring ≥ 3 years from enrollment. Long-term risk for serous EOC was reduced in women with low CA125 and high anti-CA125 antibodies relative to women with low concentrations of both.Conclusions: We found general support for the hypothesis that anti-mucin antibody levels correlate with risk factors for EOC. Antibodies alone or in combinations with their antigen may predict longer term risk of specific EOC types.Impact: Anti-CA125 and anti-CA15.3 antibodies alone or in perspective of antigens may be informative in the pathogenesis of EOC subtypes, but less useful for informing risk for all EOC. Cancer Epidemiol Biomarkers Prev; 27(7); 790-804. ©2018 AACR.

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