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Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation.

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Title: Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation.
Authors: Kaaks, R
Fortner, RT
Hüsing, A
Barrdahl, M
Hopper, M
Johnson, T
Tjønneland, A
Hansen, L
Overvad, K
Fournier, A
Boutron-Ruault, M-C
Kvaskoff, M
Dossus, L
Johansson, M
Boeing, H
Trichopoulou, A
Benetou, V
La Vecchia, C
Sieri, S
Mattiello, A
Palli, D
Tumino, R
Matullo, G
Onland-Moret, NC
Gram, IT
Weiderpass, E
Sánchez, M-J
Navarro Sanchez, C
Duell, EJ
Ardanaz, E
Larranaga, N
Lundin, E
Idahl, A
Jirström, K
Nodin, B
Travis, RC
Riboli, E
Merritt, M
Aune, D
Terry, K
Cramer, DW
Anderson, KS
Item Type: Journal Article
Abstract: Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.
Issue Date: 1-Feb-2018
Date of Acceptance: 1-Feb-2018
URI: http://hdl.handle.net/10044/1/60621
DOI: https://dx.doi.org/10.1002/ijc.31335
ISSN: 0020-7136
Publisher: Wiley
Start Page: 515
End Page: 526
Journal / Book Title: International Journal of Cancer
Volume: 143
Issue: 3
Copyright Statement: © 2018 UICC. This is the accepted version of the following article: Tumor-associated autoantibodies as early detection markers forovarian cancer? A prospective evaluation, Int. J. Cancer: 143, 515–526, which has been published in final form at https://dx.doi.org/10.1002/ijc.31335
Keywords: antibodies
early detection
prospective validation
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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