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

Fortner, Renée T.; Schock, Helena; Le Cornet, Charlotte; Hüsing, Anika; Vitonis, Allison F.; Johnson, Theron S.; Fichorova, Raina N.; Fashemi, Titilayo; Yamamoto, Hidemi S. and Tjønneland, Anne, et al. (2018) In International Journal of Cancer 142(7). p.1355-1360
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... (More)

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.

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keywords
anti-CA125 antibodies, autoantibodies, CA125, early detection markers, MUC16, ovarian cancer
in
International Journal of Cancer
volume
142
issue
7
pages
6 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:85041834082
ISSN
0020-7136
DOI
10.1002/ijc.31164
language
English
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yes
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011e0c84-baf3-43f0-961d-5e00b58414a2
date added to LUP
2018-02-20 13:31:47
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2018-05-29 10:21:50
@article{011e0c84-baf3-43f0-961d-5e00b58414a2,
  abstract     = {<p>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 &lt;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]; p<sub>het</sub> = 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.</p>},
  author       = {Fortner, Renée T. and Schock, Helena and Le Cornet, Charlotte and Hüsing, Anika and Vitonis, Allison F. and Johnson, Theron S. and Fichorova, Raina N. and Fashemi, Titilayo and Yamamoto, Hidemi S. and Tjønneland, Anne and Hansen, Louise and Overvad, Kim and Boutron-Ruault, Marie Christine and Kvaskoff, Marina and Severi, Gianluca and Boeing, Heiner and Trichopoulou, Antonia and Papatesta, Eleni Maria and La Vecchia, Carlo and Palli, Domenico and Sieri, Sabina and Tumino, Rosario and Sacerdote, Carlotta and Mattiello, Amalia and Onland-Moret, N. Charlotte and Peeters, Petra H. and Bueno-de-Mesquita, H. Bas and Weiderpass, Elisabete and Quirós, J. Ramón and Duell, Eric J. and Sánchez, Maria Jose and Navarro, Carmen and Ardanaz, Eva and Larrañaga, Nerea and Nodin, Björn and Jirström, Karin and Idahl, Annika and Lundin, Eva and Khaw, Kay Tee and Travis, Ruth C. and Gunter, Marc and Johansson, Mattias and Dossus, Laure and Merritt, Melissa A. and Riboli, Elio and Terry, Kathryn L. and Cramer, Daniel W. and Kaaks, Rudolf},
  issn         = {0020-7136},
  keyword      = {anti-CA125 antibodies,autoantibodies,CA125,early detection markers,MUC16,ovarian cancer},
  language     = {eng},
  month        = {04},
  number       = {7},
  pages        = {1355--1360},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels : Results from the EPIC cohort},
  url          = {http://dx.doi.org/10.1002/ijc.31164},
  volume       = {142},
  year         = {2018},
}