Abstract
In Europe ovarian cancer represents the third most common cancer of the female genital tract, with 30,000 newly diagnosed patients per year. Family history is the most significant risk factor. Lifetime risk for ovarian cancer increases from 1.4% for women with a negative family history to 14.6-32.2% in women from affected families. About 5-10% of ovarian cancers are hereditary and supposed to occur in three different forms: hereditary breast and ovarian cancer syndrome (HBOC), site-specific hereditary ovarian cancer (HOC) and hereditary nonpolyposis colorectal cancer syndrome (HNPCC). HBOC and HOC account for 80-90% of the cases and are associated with inactivating germline mutations of the BRCA1 and BRCA2 genes. For BRCA1 and BRCA2 mutation carriers the cumulative risk by age 70 of developing ovarian cancer is 45-60% and 25-30%, respectively. Approximately 10-15% of familial ovarian cancers are related to the HNPCC syndrome with a cumulative ovarian cancer risk of 9% by age 70. Germline polymorphisms may further modify ovarian cancer risk. Bilateral prophylactic oophorectomy reduces the risk of developing ovarian cancer in HBOC and HOC families by 50%. Tubal ligation also significantly reduces the risk in BRCA1 mutation carriers (odds ratio 0.39). Knowledge of the genetic background provides an objective basis for individual risk assessment and prevention.
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