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

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Title: Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: results from the EPIC cohort
Authors: Fortner, RT
Schock, H
Le Cornet, C
Hüsing, A
Vitonis, AF
Johnson, TS
Fichorova, RN
Fashemi, T
Yamamoto, HS
Tjønneland, A
Hansen, L
Overvad, K
Boutron-Ruault, M-C
Kvaskoff, M
Severi, G
Boeing, H
Trichopoulou, A
Papatesta, E-M
La Vecchia, C
Palli, D
Sieri, S
Tumino, R
Sacerdote, C
Mattiello, A
Onland-Moret, NC
Peeters, PH
Bueno-de-Mesquita, HBA
Weiderpass, E
Quirós, JR
Duell, EJ
Sánchez, M-J
Navarro, C
Ardanaz, E
Larrañaga, N
Nodin, B
Jirström, K
Idahl, A
Lundin, E
Khaw, K-T
Travis, RC
Gunter, M
Johansson, M
Dossus, L
Merritt, MA
Riboli, E
Terry, KL
Cramer, DW
Kaaks, R
Item Type: Journal Article
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 4 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 towards 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. This article is protected by copyright. All rights reserved.
Issue Date: 11-Dec-2017
Date of Acceptance: 26-Oct-2017
URI: http://hdl.handle.net/10044/1/54285
DOI: https://dx.doi.org/10.1002/ijc.31164
ISSN: 0020-7136
Publisher: Wiley
Start Page: 1355
End Page: 1360
Journal / Book Title: International Journal of Cancer
Volume: 142
Issue: 7
Copyright Statement: © 2017 UICC. This is the accepted version of the following article, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/ijc.31164/abstract
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
ovarian cancer
early detection markers
CA125
anti-CA125 antibodies
MUC16
autoantibodies
TUMOR-ASSOCIATED ANTIGENS
IMMUNE-COMPLEXES
BIOMARKERS
DIAGNOSIS
LUNG
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Conference Place: United States
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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