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.
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.
For both cases and controls: the presence of concurrent malignancies other from OC.
Cases and controls enrolment will be conducted in the ovarian cancer and rheumatology outpatient clinics of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, respectively.
Case-control
Prospective
Polygenic Risk Score
GeneticFor 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.
Biopsy on normal contralateral ovary
Diagnostic testDuring 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).
Pharmacogenetic profiles
GeneticIdentifying 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.
Full-Field Optical Coherence Tomography (FF-OCT), combined with Dynamic Cell Imaging (Van Gogh System) on detecting ovarian cancer lesions from tissue samples
Diagnostic testTissue 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.
Odds of developing EOC by different PRS percentiles
Correlation between PRS percentiles and EOC risk
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.
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.
Frequency of functional genotypes in drug-metabolizing enzymes and transporters
Number of genes associated with treatment response identified
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Catholic University of the Sacred Heart
Lead sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Collaborator
