A case-control study involving personal interviews of approximately 300 women with recently diagnosed and uniformly classified ovarian cancers and 300 general population controls will assess the following epidemiologic risk factors: diet using semiquantitative food frequency questionnaires with particular emphasis on animal and vegetable fat and vitamins, genital exposure to talc from use as body or dusting powder, reproductive history including use of contraceptive and noncontraceptive hormones, use of phenobarbital and antidepressants, and family and childhood history to be confirmed whenever possible by self-administered questionnaires in mothers of cases and controls. Biologic studies will be performed in the same population to measure: serum antibody levels to mumps, galactose transferase activity in whole blood, urinary gonadotropin levels in post-menopausal subjects and selenium levels in specimens of toenails. More elaborate studies on the subset of patients from the Brigham and Women's Hospital and Massachusetts General Hospital will include: extensive histochemical characterization and ennumeration of inclusion cysts in ovaries of cases and surgical controls and analysis of fat biopsy specimens for fatty acids as an indicator of past diet. These studies are designed to test the following theory for the pathogenesis of ovarian cancer. Entrapment of multipotent surface epithelium into the hormonally active stroma of the ovary occurs first followed by differentiation and proliferation of the entrapped epithelium mediated by estrogen or estrogen precursors. The estrogen may come from extraglandular sources as from high fat diets, for example, or from intraglandular sources consequent to high gonadotropins. In turn, high gonadotropins may derive from premature ovarian failure or from substances which cause increased hepatic degradation of estrogen and interfere with normal pituitary-ovarian feedback. This study combines epidemiologic and biologic markers in a coherent test of this theory. If confirmed this model could offer several approaches for the primary or secondary prevention of a disease which takes lives of more than 11,000 American women each year.
