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

Cancer Chemother Pharmacol. 2019 Dec;84(6):1219-1227. doi: 10.1007/s00280-019-03933-z. Epub 2019 Sep 16.

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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 (p = 0.004). No significant association of proteinuria with IL-8 SNP or hypertension with selected eNOS and IL-8 SNPs was found.

Conclusions: 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: Adverse events; Bevacizumab; Breast cancer; Pharmacogenetics; Polymorphisms; Proteinuria; eNOS.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Bevacizumab / adverse effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension / chemically induced
  • Hypertension / epidemiology
  • Hypertension / genetics
  • Interleukin-8 / genetics
  • Kaplan-Meier Estimate
  • Middle Aged
  • Nitric Oxide Synthase Type III / genetics*
  • Polymorphism, Single Nucleotide
  • Progression-Free Survival
  • Proteinuria / chemically induced*
  • Proteinuria / epidemiology
  • Proteinuria / genetics
  • Proteinuria / urine

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • Bevacizumab
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III