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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 >or=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.

Many cancers, including ovarian, overexpress epithelial mucin (MUC1) and promote anti-MUC1 antibodies that may correlate with more favorable prognosis. By extension, risk for ovarian cancer might be reduced by preexisting MUC1-specific immunity. We measured anti-MUC1 antibodies in 705 control women, identified events predicting antibodies, and estimated ovarian cancer risk by comparing profiles of events generating antibodies in controls with those in 668 ovarian cancer cases. Factors predicting antibodies included oral contraceptive use, breast mastitis, bone fracture or osteoporosis, pelvic surgeries, nonuse of talc in genital hygiene, and to a lesser extent intrauterine device use and current smoking. There was a significant increase in the likelihood of having anti-MUC1 antibodies from 24.2% in women with 0 or 1 condition, to 51.4% in those with five or more conditions. By the same index of events, the risk for ovarian cancer was inversely associated with number of conditions predisposing to anti-MUC1 antibodies. Compared with having experienced 0 or 1 event, the adjusted risk for ovarian cancer decreased progressively with relative risks (and 95% confidence limits) of 0.69 (0.52-0.92), 0.64 (0.47-0.88), 0.49 (0.34-0.72), and 0.31 (0.16-0.61), respectively for women with two, three, four, and five or more events related to the presence of antibodies (P(trend) < 0.0001.) We conclude that several traditional and new risk factors for ovarian cancer may be explained by their ability to induce MUC1 immunity through exposure of MUC1 to immune recognition in the context of inflammatory or hormonal processes in various MUC1-positive tissues.