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Incessant Ovulation, Mucin 1 Immunity, and Risk for Ovarian Cancer

¹ Obstetrics and Gynecology Epidemiology Center and ² Department of Pathology (Women's and Perinatal Pathology Division), Brigham and Women's Hospital, Boston, Massachusetts; ³ Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; and ⁴ Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Requests for reprints: Kathryn Terry, Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115. Phone: 617-732-8596; Fax: 617-732-4899. E-mail: kterry{at}hsph.harvard.edu

Background: Risk for ovarian cancer correlates directly with "ovulatory years or cycles" estimated from time not pregnant, breast-feeding, or using oral contraceptives. Recently, we reported that several factors known to reduce ovarian cancer risk may operate by inducing antibodies against mucin 1 (MUC1), a glycoprotein overexpressed in ovarian cancer. Conversely, other events might increase risk by interfering with the development of protective immunity. In this study, we examined whether the total number of ovulatory cycles decreases the likelihood of anti-MUC1 antibodies and provides an immune basis for the association between "incessant ovulation" and ovarian cancer risk.

Methods: From 1998 to 2003, we enrolled 668 epithelial ovarian cancer cases and 721 controls residing in eastern Massachusetts or New Hampshire, collected information on menstrual and reproductive events, and obtained blood samples from controls to measure anti-MUC1 antibodies. Using logistic regression, we calculated odds ratios to evaluate the influence of reproductive factors, including the estimated lifetime number of ovulatory cycles on ovarian cancer risk and on the presence of MUC1 antibodies in controls.

Results: Overall, we observed that early age at first birth, cycle lengths 30 days, and oral contraceptive use increased the likelihood of having anti-MUC1 antibodies. Estimated ovulatory cycles were correlated positively with ovarian cancer risk and inversely with the presence of anti-MUC1 antibodies among controls ages 46 to 60 years.

Conclusions: These data suggest that suppression of MUC1-specific immunity should be considered as an additional explanation for the observation that ovarian cancer risk increases with the lifetime number of ovulatory cycles. (Cancer Epidemiol Biomarkers Prev 2007;16(1):30–5)

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