Implications of venous thromboembolism GWAS reported genetic makeup in the clinical outcome of ovarian cancer patients

Abstract

Ovarian cancer (OC) represents the most lethal gynaecological neoplasia. Conversely, venous thromboembolism (VTE) and OC are intricately connected, with many haemostatic components favouring OC progression. In light of this bilateral relationship, genome-wide association studies (GWAS) have reported several single-nucleotide polymorphisms (SNPs) associated with VTE risk that could be used as predictors of OC clinical outcome for better therapeutic management strategies. Thus, the present study aimed to analyse the impact of VTE GWAS-identified SNPs on the clinical outcome of 336 epithelial ovarian cancer (EOC) patients. Polymorphism genotyping was performed using the TaqMan® Allelic Discrimination methodology. Carriers with the ZFPM2 rs4734879 G allele presented a significantly higher 5-year OS, 10-year OS and disease-free survival (DFS) compared to AA genotype patients with FIGO I/II stages (P = 0.009, P = 0.001 and P = 0.003, respectively). Regarding SLC19A2 rs2038024 polymorphism, carriers with the CC genotype presented a significantly lower 5-year OS, 10-year OS and DFS compared to A allele carriers in the same FIGO subgroup (P < 0.001, P = 0.004 and P = 0.005, respectively). As for CNTN6 rs6764623 polymorphism, carriers with the CC genotype presented a significantly lower 5-year OS compared to A allele carriers with FIGO I/II stages (P = 0.015). As for OTUD7A rs7164569, F11 rs4253417 and PROCR rs10747514, no significant impact on EOC patients’ survival was observed. However, future studies are required to validate these results and uncover the biological mechanisms underlying our results.

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Fig. 1: Association between ZFPM2 rs4734879 polymorphism and patients’ survival.
Fig. 2: Association between SLC19A2 rs2038024 polymorphism and patients’ survival.
Fig. 3: Association between CNTN6 rs6764623 polymorphism and patients’ 5-year overall survival.

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Acknowledgements

We would like to thank the Liga Portuguesa Contra o Cancro-Centro Regional do Norte (LPCC-NRN2020-VT), Ministério da Saúde de Portugal (CFICS-45/2007), IPO-Porto Projects (CI-IPOP-22-2015 and CI-IPOP-91-2018) and Fundação para a Ciência e Tecnologia (FCT).

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Tavares, V., Pinto, R., Assis, J. et al. Implications of venous thromboembolism GWAS reported genetic makeup in the clinical outcome of ovarian cancer patients. Pharmacogenomics J (2020). https://doi.org/10.1038/s41397-020-00201-9

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