Puerperal mastitis: a reproductive event of importance affecting anti-mucin antibody levels and ovarian cancer risk
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Test the hypothesis that puerperal mastitis may alter immunity related to the mucin (MUC) family of glycoproteins and lower risk of ovarian cancer.
In two case–control studies conducted in New England between 1998 and 2008, we examined the association between self-reported mastitis and ovarian cancer in 1,483 women with epithelial ovarian cancer and 1,578 controls. IgG1 antibodies against (MUC1) CA15.3 and (MUC16) CA125 were measured using electrochemiluminescence assays in a subset of controls (n = 200). Preoperative CA125 was recorded in 649 cases. The association between ovarian cancer and mastitis was assessed using unconditional logistic regression to calculate adjusted odds ratios, OR, and 95 % confidence intervals (CI). Associations between mastitis and anti-CA15.3 and anti-CA125 antibodies and preoperative CA125 levels were evaluated using adjusted linear regression models.
Prior mastitis was associated with a significantly lower risk of ovarian cancer: OR (and 95 % CI) of 0.67 (0.48, 0.94) adjusted for parity, breastfeeding, and other potential confounders. The association was strongest with 2 or more episodes of mastitis, and risk declined progressively with increasing number of children and episodes of mastitis. Among controls, prior mastitis was associated with significantly higher anti-CA15.3 and anti-CA125 antibody levels and, among cases, with significantly lower preoperative CA125 levels.
Puerperal mastitis may produce long-lasting anti-mucin antibodies that may lower the risk of ovarian cancer, plausibly through enhanced immune surveillance. Studying immune reactions related to MUC1 and MUC16 in the 10–20 % of breastfeeding women who develop mastitis may suggest ways to duplicate its effects through vaccines based on both antigens.
KeywordsCA125 CA15.3 Ovarian cancer Puerperal mastitis
We acknowledge Professor Olivera J. Finn for her support of our prior studies of mucin immunity and ovarian cancer and her thoughtful input on this manuscript. We thank John R. McKolanis for his technical advice on the anti-mucin assays, and Hassan Y. Dawood, B.S. for performing the anti-CA125 and anti CA15.3 immunoassays in Dr. Fichorova’s laboratory. This work is dedicated to the memory of Katherine Astrove in recognition of her husband’s long-term support of research on ovarian cancer at the Brigham and Women’s Hospital. This research was supported by the National Institutes of Health (Grant numbers. R01CA123170, R01CA54419, and P50CA105009 to DWC) and donations from Mr. Edgar Astrove.
Conflict of interest
Daniel W. Cramer is a plantiff’s witness in litigation related to ovarian cancer. The remaining authors declare that they have no conflict of interest.
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