Ovarian surface epithelium: family history and early events in ovarian cancer.

Ovarian cancer is the most common cause of death from gynecological cancers in the Western world. There are many genetic and environmental factors which can influence a woman's risk of getting ovarian cancer. A strong family history of breast or ovarian cancer is definitely one of the most important and best-defined epidemiological risk factors. This review evaluates current knowledge of hereditary ovarian cancer. Histologic, cytologic and molecular studies on the ovarian surface epithelium (OSE), which is the origin of ovarian epithelial carcinomas, from women with a strong family history for ovarian carcinomas or with a mutation in one of the two known cancer susceptibility genes - BRCA1 and BRCA2, provide a background to facilitate understanding of the early changes in ovarian carcinogenesis. This overview is followed by a discussion of recent hypotheses and research on two questions. First, is there a mutational hotspot of BRCA mutation for ovarian cancer? Second, why do mutations in BRCA1 and BRCA2, which are ubiquitously expressed genes that participate in general cellular activities, lead preferentially to breast and ovarian cancer?