HEREDITARY OVARIAN-CANCER - MOLECULAR-GENETICS AND CLINICAL IMPLICATIONS

Epidemiologic data support the existence of two discrete manifestation s of hereditary ovarian carcinoma: the breast and ovarian cancer syndr ome and the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome . Genetic linkage analyses reveal that the majority of breast and ovar ian cancer families are Linked to the BRCA1 gene, while some cases of hereditary ovarian cancer are also apparent in breast cancer families linked to the BRCA2 gene. The majority of HNPCC families are linked to one of four genes encoding a family of DNA mismatch repair proteins. Molecular analyses demonstrate that genetic screening for germline tra nsmission of a defective allele of one or another of these genes is no w possible for high-risk individuals. The ethical, legal, and social i mplications of this type of analysis are multiple and complex, and gen etic counseling requires a thorough understanding of these issues and a cautious approach to most effectively meet the special needs of this patient population. Increased medical surveillance and prophylactic o ophorectomy are among the management options that may be appropriate f or some genetically predisposed, asymptomatic women. Further research is needed regarding the most effective use of this genetic information in formulating counseling and clinical management strategies. (C) 199 7 Academic Press.