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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5481 - DNA Repair genetic profiling in epithelial ovarian cancer: an opportunity for clinical improvement?

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Joana Assis

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

J. Assis1, S. Coelho2, A. Nogueira1, R. Pinto1, M. Brandao3, J. Dias2, S.G.C.M. Alves2, D. Pereira2, R. Medeiros1

Author affiliations

  • 1 Grupo De Oncologia Molecular E Patologia Viral - Centro De Investigação, Instituto Portugues de Oncologia Centro do Porto(IPO-Porto), 4200-072 - Porto/PT
  • 2 Medical Oncology, Instituto Portugues de Oncologia Centro do Porto(IPO-Porto), 4200-072 - Porto/PT
  • 3 Ctsu, Institute Jules Bordet, 1000 - Brussels/BE
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Resources

Abstract 5481

Background

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.

Methods

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.

Results

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.

Conclusions

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

IPO-Porto.

Funding

Liga Portuguesa Contro Cancro-Centro Regional do Norte; IPO-Porto (CI-IPOP-22-2015); Fundação para a Ciência e Tecnologia (FCT).

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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