The molecular genetics of sporadic and familial epithelial ovarian cancer

Progress in investigating the molecular basis of cancer has been rapid during recent years and has resulted in important advances in understanding ovarian carcinogenesis. These include the isolation of highly penetrant cancer susceptibility genes and the identification of alterations in other genetic elements involved in cell growth, differentiation and DNA repair. The first section of this review describes the epidemiology and genetics of familial ovarian cancer and the identification of the BRCA1 gene associated with breast/ovarian cancer and of the DNA repair genes associated with the Lynch II syndrome. The risk of cancer associated with germ line abnormalities of these genes and the management options for women with a family history of ovarian cancer are discussed. The second section describes genetic abnormalities associated with sporadic ovarian cancer. Although a detailed multistep pathway of sporadic ovarian carcinogenesis cannot yet be described a number of specific abnormalities have now been documented. These include abnormalities of growth factors (M-CSF, TGF-beta), growth factor receptors (c-fins, EGFR, Her-2/neu), genes involved in signal transduction (Ki-ras), and genes involved in transcriptional regulation (c-myc, p53) and loss of heterozygosity at various chromosomal loci. The final section of the review discusses the genetics of metastatic disease, candidate precursor lesions for ovarian cancer and the field change hypothesis of ovarian carcinogenesis.