Anti-CA15.3 and anti-CA125 antibodies and ovarian cancer risk: Results from the EPIC cohort

Daniel W Cramer, Raina N Fichorova, Kathryn L Terry, Hidemi Yamamoto, Allison F Vitonis, Eva Ardanaz, Dagfinn Aune, Heiner Boeing, Jenny Brändstedt, Marie-Christine Boutron-Ruault, Maria-Dolores Chirlaque, Miren Dorronsoro, Laure Dossus, Eric J Duell, Inger T Gram, Marc Gunter, Louise Hansen, Annika Idahl, Theron Johnson, Kay-Tee Khaw, Vittorio Krogh, Marina Kvaskoff, Amalia Mattiello, Giuseppe Matullo, Melissa A Merritt, Björn Nodin, Philippos Orfanos, N Charlotte Onland-Moret, Domenico Palli, Eleni Peppa, J Ramón Quirós, Maria-Jose Sánchez-Perez, Gianluca Severi, Anne Tjønneland, Ruth C Travis, Antonia Trichopoulou, Rosario Tumino, Elisabete Weiderpass, Renée T Fortner, Rudolf Kaaks

Neoplastic and non-neoplastic events may raise levels of mucins, CA15.3 and CA125, and generate antibodies against them; but their impact on epithelial ovarian cancer (EOC) risk has not been fully defined. CA15.3, CA125, and IgG1 antibodies against them were measured in 806 women who developed EOC and 1,927 matched controls from the European Prospective Investigation of Nutrition and Cancer. Associations between epidemiologic factors and anti-mucin antibodies were evaluated using generalized linear models; EOC risks associated with anti-mucin antibodies, by themselves or in combination with respective antigens, were evaluated using conditional logistic regression. In controls, lower antibodies against both mucins were associated with current smoking; and, in postmenopausal women, higher levels with longer oral contraceptive use and later-age-at and shorter-interval-since last birth. Lower anti-CA15.3 antibodies were associated with higher body mass and, in premenopausal women, more ovulatory cycles. Higher anti-CA15.3 and anti-CA125 antibodies were associated with higher risk for mucinous EOC occurring ≥ 3 years from enrollment. Long-term risk for serous EOC was reduced in women with low CA125 and high anti-CA125 antibodies relative to women with low concentrations of both. We found general support for the hypothesis that anti-mucin antibody levels correlate with risk factors for EOC. Antibodies alone or in combinations with their antigen may predict longer term risk of specific EOC types. Anti-CA125 and anti- CA15.3 antibodies alone or in perspective of antigens may be informative in the pathogenesis of EOC subtypes, but less useful for informing risk for all EOC.