Evaluation of Polygenic Risk Score for Epithelial OVarian cancEr Risk Prediction: the PROVE Study

This study aims to investigate epithelial ovarian cancer (EOC) through a combined case-control and prospective cohort design, focusing on genetic, clinical, and lifestyle risk factors. The recruitment phase will last 12 months, conducted at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. Cases will include women with histologically confirmed EOC, while controls will be women without a history of ovarian cancer, consecutively recruited from the Rheumatology Unit. Eligible participants must be ≥18 years old and provide informed consent. Women with concurrent malignancies other than OC will be excluded. Study Procedures Baseline Visit After signing informed consent, participants will undergo the following assessments: * Structured Questionnaire: Collection of socio-demographic data, medical and family history, obstetric history, lifestyle factors, comorbidities, and potential ovarian cancer risk factors. * Blood Sampling: Blood will be collected for molecular analysis, including BRCA1/2 mutational status and Polygenic Risk Score (PRS) evaluation. PRS results will be available to participants upon request, while pathogenic BRCA results will be referred to a geneticist and managed according to clinical practice. A fertility-sparing approach will be considered for patients of reproductive age who express a desire for future fertility and are diagnosed with FIGO stage IA or IC1 ovarian cancer of low-grade serous, grade 1-2 endometrioid, or expansile mucinous histology. Tissue samples obtained from macroscopically normal ovarian tissue in patients undergoing fertility-sparing surgery (cases) will be analyzed ex vivo using Full-Field Optical Coherence Tomography and Dynamic Cell Imaging. For the pharmagenetics analysis, patients will be divided into different groups based on the treatment type received (i.e. PARPi, chemo, moAB) and each drug will be characterised by different groups of pharmacogenetic profiles involved in their efficacy and toxicity. The pharmacogenetic signature will also be evaluated to determine the drug-drug interaction risks in patients undergoing multiple treatments for comorbidities.