Research Abstract
Dr. Cramer's research focuses on the epidemiology of ovarian cancer with the goal of developing a model to explain risk factors for the disease and biomarkers that might correlate with risk. There are three events which increase risk for ovarian cancer that are associated with chronic inflammation affecting the lower or upper genital tract. These include: cosmetic talc powder use; repeated ovulation not interrupted by pregnancies, breastfeeding, or oral contraceptive use (incessant ovulation), and endometriosis. Besides pregnancies, breastfeeding, and oral contraceptive use that decrease ovulations, other factors that lower risk for ovarian cancer include childhood mumps, a tubal ligation, and an infection while breastfeeding (mastitis). We have assembled data to suggest that the mucin tumor biomarkers CA125(MUC16) and CA15.3(MUC1) and immune reactions related to these may be unifying biomarkers. These mucins reside on the apical surfaces of the reproductive, digestive, and genital tracts as well as breast ducts. Acute events like mumps, tubal ligation, and mastitis lead to the spillage of tumor-like forms of MUC1 and MUC16 and the production of anti-mucin antibodies that could serve to protect against mucin-secreting ovarian tumors. Conversely chronic events like talc use, incessant ovulation, and endometriosis lead to prolonged exposure to mucins, down regulation of mucin immunity, and tolerance of an emerging mucin-secreting tumor. We have developed an efficient and reliable set of assays for MUC1, MUC16, anti-MUC1 antibodies, and anti-MUC16 antibodies to assess their ability to predict short and long-term risk for ovarian cancer in large prospective data sets including the European Prospective Investigation of Nutrition and Cancer (EPIC). Finally we are developing a novel assay to quantify the amount of mucin-binding to circulating white blood cells that we believe is necessary to complete the picture of mucin immunity in relation to ovarian cancer.