TY - JOUR
TI - Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort
AU - Fortner, R.T.
AU - Schock, H.
AU - Le Cornet, C.
AU - Hüsing, A.
AU - Vitonis, A.F.
AU - Johnson, T.S.
AU - Fichorova, R.N.
AU - Fashemi, T.
AU - Yamamoto, H.S.
AU - Tjønneland, A.
AU - Hansen, L.
AU - Overvad, K.
AU - Boutron-Ruault, M.-C.
AU - Kvaskoff, M.
AU - Severi, G.
AU - Boeing, H.
AU - Trichopoulou, A.
AU - Papatesta, E.-M.
AU - La Vecchia, C.
AU - Palli, D.
AU - Sieri, S.
AU - Tumino, R.
AU - Sacerdote, C.
AU - Mattiello, A.
AU - Onland-Moret, N.C.
AU - Peeters, P.H.
AU - Bueno-de-Mesquita, H.B.
AU - Weiderpass, E.
AU - Quirós, J.R.
AU - Duell, E.J.
AU - Sánchez, M.-J.
AU - Navarro, C.
AU - Ardanaz, E.
AU - Larrañaga, N.
AU - Nodin, B.
AU - Jirström, K.
AU - Idahl, A.
AU - Lundin, E.
AU - Khaw, K.-T.
AU - Travis, R.C.
AU - Gunter, M.
AU - Johansson, M.
AU - Dossus, L.
AU - Merritt, M.A.
AU - Riboli, E.
AU - Terry, K.L.
AU - Cramer, D.W.
AU - Kaaks, R.
JO - International Journal  of Cancer
PY - 2018
VL - 142
TODO - 7
SP - 1355-1360
PB - Wiley-Liss, Inc.
SN - 0020-7136
TODO - 10.1002/ijc.31164
TODO - autoantibody;  CA 125 antigen;  CA125 autoantibody;  unclassified drug;  autoantibody;  CA 125 antigen;  membrane protein;  MUC16 protein, human;  tumor marker, adult;  aged;  area under the curve;  Article;  blood sampling;  cancer growth;  case control study;  cohort analysis;  controlled study;  correlational study;  early cancer diagnosis;  electrochemiluminescence;  female;  human;  immune response;  major clinical study;  ovary cancer;  priority journal;  blood;  early cancer diagnosis;  immunology;  middle aged;  ovary tumor;  procedures;  receiver operating characteristic;  sensitivity and specificity, Adult;  Aged;  Area Under Curve;  Autoantibodies;  Biomarkers, Tumor;  CA-125 Antigen;  Case-Control Studies;  Cohort Studies;  Early Detection of Cancer;  Female;  Humans;  Membrane Proteins;  Middle Aged;  Ovarian Neoplasms;  ROC Curve;  Sensitivity and Specificity
TODO - 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. © 2017 UICC
ER -