In a recently published systematic review and meta-analysis, we provided an updated assessment of the association between genetic polymorphisms and epithelial ovarian cancer (EOC) first-line treatment outcome. Results highlighted the role of DNA Repair mediators, namely for variants in ERCC1 and ERCC2. Therefore, this study aims to evaluate the role of ERCC1 (rs11615 and rs3212986) and ERCC2 (rs13181 and rs1799793) variants in the outcome of EOC patients.
We conducted a hospital-based study in a cohort of EOC patients submitted to platinum-based first-line treatment (n = 340). DNA was extracted from peripheral blood samples, and genotypes were determined by Real-Time PCR using validated assays. Overall survival (OS) was the primary endpoint of this analysis. Survival analyses using Kaplan-Meier method and Cox proportional-hazards model were applied and the statistical significance was set at p < 0.05.
The definition of a genetic profile reveals that patients harboring the combination of ERCC1 rs11615 A allele/ERCC1 rs3212986 AA genotype/ERCC2 rs13181 T allele/ERCC2 rs1799793 C allele have a significantly lower survival when compared to other genotype patients (136 vs. 161 months; log-rank test, P = 0.034). Specifically, this genetic profile is associated with a poorer prognosis (26 months vs. 69 months, respectively; log-rank test, P = 0.036) and a higher risk of death (HR, 2.7; Pbootstrap=0.019) among FIGO stage IV patients.
In an era where DNA repair ability is stated as a major cornerstone in EOC management, the characterization and definition of a DNA repair profile might be a useful tool for EOC clinical outcome prediction. According to the results of a meta-analysis, we validate the influence of ERCC1 and ERCC2 genetic polymorphisms in the survival of EOC patients submitted to platinum-based first-line chemotherapy. Particularly, this profile seems to have a preponderant role for the subgroup of advanced disease patients. Further considerations should be applied for the functional evaluation of these mediators in this clinical setting, as they might reveal an opportunity to improve survival in a subgroup with unfavorable prognosis.
Clinical trial identification
Legal entity responsible for the study
Liga Portuguesa Contro Cancro-Centro Regional do Norte; IPO-Porto (CI-IPOP-22-2015); Fundação para a Ciência e Tecnologia (FCT).
All authors have declared no conflicts of interest.