The cause of ovarian cancer is unknown. Some have speculated that an etiologic agent or a potentiator of oncogenesis could enter the peritoneal cavity through the lower genital canal and spread through the uterus and the fallopian tubes. Possible carcinogens, such as infectious agents and chemical carcinogens have been studied, and while case-control studies have failed to document a specific agent, some studies have linked environmental exposure to asbestos-contaminated talc in douches and contraceptives with the development of epithelial tumors. Case control studies have also pointed to an association of white race, high-fat diet and galactose consumption with a higher incidence of the disease.
Among the epidemiological variables, however, prior reproductive history and the number of ovulatory cycles appear to have the greatest impact on development of the disease, with low parity, infertility, early menarche and late menopause increasing the risk. Fertility enhancing drugs, such as clomiphene citrate and gonadotropins used for ovulation induction have been thought to increase the risk of ovarian cancer, but the data have not been consistent and have not adequately distinguished the influence of infertility per se from the use of fertility stimulating agents. A pooled analysis of eight case-control studies that included 5,207 cases and 7,705 controls found an association of fertility stimulating drugs with serous borderline tumors, but not with invasive ovarian cancers. The increased incidence of ovarian cancer in single women, nuns, and nulliparous women suggests that continual ovulation, uninterrupted by pregnancy, may predispose women to develop this malignancy. Over many cycles of ovulation, the ovarian surface epithelium undergoes repetitive disruption and repair. Epithelial cells covering the ovarian surface are stimulated to proliferate, increasing the probability of spontaneous mutations in tumor suppressor or proto-oncogenes that might contribute to oncogenesis. Alternatively, trapping of epithelial cells within the stroma following ovulation can lead to the formation of inclusion cysts where epithelial cells are subjected to a unique microenvironment.
Most case control and cohort studies have failed to link hormone replacement therapy to an increased risk of epithelial ovarian cancer. One large cohort study has recently re-opened controversy regarding this issue. Among 44,241 postmenopausal women in the Breast Cancer Detection Demonstration Project, 329 developed ovarian cancer. Women who had received estrogen replacement therapy only, without progestin, for more than 10 years were at increased risk of developing ovarian cancer. By 20 years the relative risk was 3.2 fold.
- Epithelial Ovarian Cancer
- Etiology and Epidemiology
- Genetic Risk for Epithelial Ovarian Cancer
- Biology and Prognosis of Ovarian Neoplasms
- Classification and Pathology
- Patterns of Spread
- Clinical Features
- Staging of Ovarian Cancer
- Treatment of Early Stage Ovarian Cancer
- Treatment of Advanced Stage Epithelial Ovarian Cancer
- Assessment of Response in Patients who are Clinically free of Disease
- Survival of Patients with Advanced Ovarian Cancer
- Nonepithelial Ovarian Cancer
The incidence of ovarian cancer varies in different geographic locations throughout the world. Western countries, including the United States and the United Kingdom, have an incidence of ovarian cancer that is three to seven times greater than in Japan, where epithelial ovarian tumors are considered rare. In Asia, the incidence of germ cell tumors of the ovary appears to be somewhat higher than in the West. Japanese immigrants to the United States, however, have a significant increase in the incidence of epithelial ovarian cancer at a rate approaching that of white women from the United States. The incidence of epithelial tumors is about one and one half times greater in whites than in blacks.
Revision date: June 22, 2011
Last revised: by Janet A. Staessen, MD, PhD