RecruitingNCT06935344

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

Evaluation of Polygenic Risk Score for Epithelial OVarian cancEr Risk Prediction and Clinical Outcomes in an Italian Population: the PROVE Study

Sponsor

Catholic University of the Sacred Heart

Enrollment

1,300 participants

Start Date

Jun 1, 2025

Study Type

OBSERVATIONAL

Conditions

Ovarian Cancer

Summary

The goal of this observational study is to evaluate whether polygenic risk score (PRS) assessment can help predict the onset of epithelial ovarian cancer in women aged over 18, comparing those with a histologically confirmed diagnosis of epithelial ovarian or fallopian tube cancer (cases) to women with no personal history of ovarian cancer (controls). The main questions it aims to answer are: * Is there an association between PRS and the presence of epithelial ovarian cancer? * Can PRS improve the prediction of ovarian cancer risk when adjusted for other clinical factors? Researchers will compare PRS values between cases and controls to see if higher PRS percentiles are associated with an increased risk of ovarian cancer. Participants will: * Complete a questionnaire on socio-economic status, lifestyle, and dietary habits. * Undergo blood sampling, for the analysis of BRCA1-2, PALB2, RAD51C, RAD51D pathogenic variants. * Undergo PRS analysis.

Eligibility

Sex: FEMALEMin Age: 18 Years

Inclusion Criteria2

For cases: women with a first-time diagnosis of histologically confirmed epithelial ovarian or fallopian tube cancer.
For Controls women with no concomitant or past OC diagnosis.

Exclusion Criteria1

For both cases and controls: the presence of concurrent malignancies other from OC.

Interventions

GENETICPolygenic Risk Score

For the PRS analysis, SNPs for genotyping will be selected based on the latest findings from GWAS on EOC, particularly leveraging the results, as reported by Dareng et al. (doi:10.1038/s41431-021-00987-7). The PRS will be calculated as a weighted sum of risk alleles based on the selected SNPs.

DIAGNOSTIC_TESTBiopsy on normal contralateral ovary

During fertility-sparing surgery for early-stage ovarian cancer, tissue samples will be obtained from macroscopically normal ovarian tissue and analyzed ex vivo using Full-Field Optical Coherence Tomography (FF-OCT) combined with Dynamic Cell Imaging (DCI). The analysis will be performed with the VanGogh biopsy system (AQUYRE Biosciences).

GENETICPharmacogenetic profiles

Identifying distinct pharmacogenetic profiles associated with different responses and toxicities from standard treatments. 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 genetic fingerprints involved in the absorption, distribution, metabolism and elimination of administered drugs will be evaluated to retrospectively correlate the efficacy and the safety profile of therapies and the expected enzymatic activity of patients.

DIAGNOSTIC_TESTFull-Field Optical Coherence Tomography (FF-OCT), combined with Dynamic Cell Imaging (Van Gogh System) on detecting ovarian cancer lesions from tissue samples

Tissue samples retrieved during surgery in eligible patients will be analyzed ex vivo using Full-Field Optical Coherence Tomography and Dynamic Cell Imaging. Samples will be assessed without any alteration, damage, or need for fixation, and this procedure will not interfere with the standard diagnostic workflow.