Modern Trends into the Epidemiology and Screening of Ovarian Cancer. Genetic Substrate of the Sporadic Form

Ovarian cancer (OC) is a heterogeneous disease, including a broad spectrum of histological subtypes and demonstrating diverse biological behavior. Epithelial-derived ovarian malignant tumours constitute the predominant and most lethal form of the disease. Age, genetic predisposition, gynecological and reproductive factors and environmental factors are the main risk factors that increase the risk for acquiring OC. Vaginal examination, ultrasonography and measurement of blood serum levels of tumour markers, especially CA125 constitute the first-line screening modalities for OC, whereas second-line testing involves more accurate imaging techniques such as color Doppler ultrasound of the lesion or/and a CT scan. Sex steroid hormone pathway genes, cell cycle genes, DNA repair genes, oncogenes and onco-suppressor genes have been associated with a genetic susceptibility to sporadic OC. In the present review we focus on the major oncogenes and onco-suppressor genes in the sporadic form of the disease. Each tumour subtype is associated with a unique molecular signature, as revealed by current genetic and biomarker profiling studies. Different OC pathways emerge early in the process of carcinogenesis, ultimately leading to clinically different tumour types. As mutations acquired early during tumourigenesis will be present in all later stages, large-scale gene expression profiling using DNA microarray analysis techniques can help to classify ovarian cancers into clinically relevant subtypes.