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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer
• Intervention / Treatment: Genetic: Polygenic Risk Score; Diagnostic test: Biopsy on normal contralateral ovary; Genetic: Pharmacogenetic profiles; Diagnostic test: Full-Field Optical Coherence Tomography (FF-OCT), combined with Dynamic Cell Imaging (Van Gogh System) on detecting ovarian cancer lesions from tissue samples

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 1300

Contacts and Locations

• Study Contact: Name: Stefania Boccia; Phone Number: +39 0630154396; Email: stefania.boccia@unicatt.it

Study Locations

• Italy
  • Italia
    • Roma, Italia, Italy, 00168
      • Recruiting
      • Dipartimento Universitario di Scienze della Vita e Sanità Pubblica
      • Contact: Stefania Boccia; Phone Number: 0630154396; Email: stefania.boccia@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Cases and controls enrolment will be conducted in the ovarian cancer and rheumatology outpatient clinics of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, respectively.

Description

Inclusion Criteria:

• 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 Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CASES: women with ovarian cancer; Patients with histologically proven epithelial ovarian and fallopian tube cancer (referred to as cases), consecutively enrolled in the Ovarian Carcinoma Complex Operative Unit of Policlinico Gemelli.	Genetic: Polygenic 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 test: Biopsy 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).; Genetic: Pharmacogenetic 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 test: Full-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.; Other Names: biopsy
CONTROLS: Healthy women; Women with no previous or concomitant personal history of OC (referred as controls), consecutively enrolled in the Rheumatology Complex Operative Unit of Policlinico Gemelli.	Genetic: Polygenic 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Odds of developing EOC by different PRS percentiles	Correlation between PRS percentiles and EOC risk	At enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of PRS percentiles and covariates	Correlation between PRS percentiles and: age, familiarity with OC, stage, histotype, grading (1-2 versus 3), BRCA1-2, PALB2, RAD51C, RAD51D, FANCM status, type of surgery, residual tumor (RT) at histology, type of chemotherapy, maintenance, chemo-resistance, response to treatment, recurrences, progressions, cancer-specific deaths, Disease Free survival (DFS) hazard ratio (HR), Overall Survival (OS) HR.	At enrollment
Diagnostic accuracy of Full-Field Optical Coherence Tomography (FF-OCT), combined with Dynamic Cell Imaging (Van Gogh System)	The diagnostic accuracy will be assessed by estimating sensitivity, specificity, accuracy, and predictive values against the histopathological gold standard. These statistics will be derived from 2×2 contingency tables and presented with two-sided 95% CIs.	At enrollment
Frequency of functional genotypes in drug-metabolizing enzymes and transporters	Number of genes associated with treatment response identified	At enrollment

Collaborators and Investigators

• Sponsor: Catholic University of the Sacred Heart
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 20, 2025

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: ovarian cancer; case-control; polygenic risk score
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Disease Susceptibility; Genetic Predisposition to Disease; Pathological Conditions, Signs and Symptoms; Genetic Risk Score; Ovarian Neoplasms; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Biopsy
• Other Study ID Numbers: 7225 (CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No