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Endothelial nitric oxide synthase c.-813C>T predicts for proteinuria in metastatic breast cancer patients treated with bevacizumab-based chemotherapy

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To investigate the association between single nucleotide polymorphisms (SNPs) in endothelial nitric oxide synthase (eNOS) and interleukin-8 (IL-8) genes and risk of developing bevacizumab-related adverse events in metastatic breast cancer… Click to show full abstract

To investigate the association between single nucleotide polymorphisms (SNPs) in endothelial nitric oxide synthase (eNOS) and interleukin-8 (IL-8) genes and risk of developing bevacizumab-related adverse events in metastatic breast cancer (mBC) patients. mBC patients candidate to receive bevacizumab-based chemotherapy were enrolled in this pharmacogenetic study. eNOS c.-813C>T and c.894G>T, and IL-8 c.-251A>T were analyzed by real time PCR on genomic DNA extracted from peripheral blood. Univariate analysis was performed to test the association between each SNP and treatment-related toxicities. Seventy-six mBC patients were enrolled in the present study. Patients carrying the homozygous variant eNOS c.-813TT genotype showed a statistically significant occurrence of any grade proteinuria when compared to CT or CC genotypes (pā€‰=ā€‰0.004). No significant association of proteinuria with IL-8 SNP or hypertension with selected eNOS and IL-8 SNPs was found. These findings suggest an association between the eNOS c.-813C>T polymorphism and the development of proteinuria in mBC patients receiving a bevacizumab-based chemotherapy.

Keywords: bevacizumab based; endothelial nitric; nitric oxide; based chemotherapy; oxide synthase; cancer

Journal Title: Cancer Chemotherapy and Pharmacology
Year Published: 2019

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