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

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 PalliSabina Sieri, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, N Charlotte Onland-Moret, Petra H Peeters, H B As Bueno-de-Mesquita, Elisabete Weiderpass, J Ramón Quirós, Eric J Duell, Maria-Jose Sánchez, Carmen Navarro, Eva Ardanaz, Nerea Larrañaga, Björn Nodin, Karin Jirström, 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1355-1360
Number of pages6
JournalInternational Journal of Cancer
Volume142
Issue number7
DOIs
Publication statusPublished - Apr 1 2018

Keywords

  • Adult
  • Aged
  • Area Under Curve
  • Autoantibodies/blood
  • Biomarkers, Tumor/blood
  • CA-125 Antigen/blood
  • Case-Control Studies
  • Cohort Studies
  • Early Detection of Cancer/methods
  • Female
  • Humans
  • Membrane Proteins/blood
  • Middle Aged
  • Ovarian Neoplasms/diagnosis
  • ROC Curve
  • Sensitivity and Specificity

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