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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Renée T. Fortner
  • Helena Schock
  • Charlotte Le Cornet
  • Anika Hüsing
  • Allison F. Vitonis
  • Theron S. Johnson
  • Raina N. Fichorova
  • Titilayo Fashemi
  • Hidemi S. Yamamoto
  • Anne Tjønneland
  • Louise Hansen
  • Kim Overvad
  • Marie Christine Boutron-Ruault
  • Marina Kvaskoff
  • Gianluca Severi
  • Heiner Boeing
  • Antonia Trichopoulou
  • Eleni Maria Papatesta
  • Carlo La Vecchia
  • Domenico Palli
  • Sabina Sieri
  • Rosario Tumino
  • Carlotta Sacerdote
  • Amalia Mattiello
  • N. Charlotte Onland-Moret
  • Petra H. Peeters
  • H. Bas Bueno-de-Mesquita
  • Elisabete Weiderpass
  • J. Ramón Quirós
  • Eric J. Duell
  • Maria Jose Sánchez
  • Carmen Navarro
  • Eva Ardanaz
  • Nerea Larrañaga
  • Annika Idahl
  • Eva Lundin
  • Kay Tee Khaw
  • Ruth C. Travis
  • Marc Gunter
  • Mattias Johansson
  • Laure Dossus
  • Melissa A. Merritt
  • Elio Riboli
  • Kathryn L. Terry
  • Daniel W. Cramer
  • Rudolf Kaaks
Organisations
External organisations
  • German Cancer Research Centre
  • Brigham and Women's Hospital / Harvard Medical School
  • Harvard Medical School
  • Danish Cancer Society Research Center
  • Aarhus University
  • Centre for Research in Epidemiology and Population Health (CESP)
  • University of Paris-Sud
  • Stabilite genetique et oncogenese
  • Human Genetics Foundation (HuGeF)
  • German Institute of Human Nutrition
  • Hellenic Health Foundation, Athens
  • National and Kapodistrian University of Athens
  • University of Milan
  • Cancer Research and Prevention Institute (ISPO)
  • Istituto Nazionale dei Tumori
  • Azienda Sanitaria Provinciale di Ragusa
  • Citta' della Salute e della Scienza Hospital-University of Turin
  • University of Naples Federico II
  • University Medical Center Utrecht
  • Imperial College London
  • National Institute for Public Health and the Environment (RIVM)
  • UiT The Arctic University of Norway, Tromsø
  • Cancer Registry of Norway Institute of Population-Based Cancer Research
  • Karolinska Institutet
  • Folkhälsan
  • Public Health Directorate
  • Catalan Institute of Oncology
  • University of Granada
  • CIBER Epidemiology and Public Health (CIBERESP)
  • Murcia Regional Health Council
  • Health Research Institute of Navarra (IDISNA)
  • Public Health Division of Gipuzkoa
  • Umeå University
  • University of Cambridge
  • University of Oxford
  • International Agency for Research on Cancer, World Health Organization
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • anti-CA125 antibodies, autoantibodies, CA125, early detection markers, MUC16, ovarian cancer
Original languageEnglish
Pages (from-to)1355-1360
Number of pages6
JournalInternational Journal of Cancer
Volume142
Issue number7
Publication statusPublished - 2018 Apr 1
Publication categoryResearch
Peer-reviewedYes