Evaluation of microRNAs, oxidized biomolecules and polymorphisms in the CYP2E1, ABCB1 and ABCC2 genes as possible biomarkers of cisplatin-induced toxicities in head and neck cancer patients

Abstract

The most effective treatment for advanced head and neck cancer is concomitant cisplatin and radiotherapy. However, its use is limited due to its toxicities caused by oxidative stress, mainly nephrotoxicity. There is a need to identify new biomarkers of nephrotoxicity. Among the biomarkers studied, we have the microRNAs and oxidized biomolecules. In addition to these possible biomarkers, the CYP2E1 enzyme, ABCB1 and ABCC2 transporters appear to be related to cisplatin-induced oxidative stress and nephrotoxicity. The objective of this study will be to analyze microRNAS and oxidized biomolecules as possible biomarkers of nephrotoxicity and to verify the relationship of polymorphisms in the CYP2E1, ABCB1 and ABCC2 genes with oxidative stress and cisplatin-induced toxicities in head and neck cancer patients. This is an analytical, experimental, clinical, single-arm, prospective, quantitative study with non-probability sampling of the consecutive type. Head and neck cancer patients who start treatment with cisplatin and radiotherapy will be included. Nephrotoxicity, gastrointestinal toxicity, myelotoxicity, expression of plasmatic and urinary microRNAs, urinary and plasmatic oxidative stress, and polymorphisms in the CYP2E1 genes (rs3813867, rs3813865, rs8192772), ABCB1 (rs1045642, rs1128503 and Rs2032582) and ABCC2 (rs717620, rs2273697 and rs3740066) will be evaluated. Treatment response, overall survival, and disease-free survival will also be evaluated. Chi-square, Fisher exact, Mann-Whitney and ANOVA tests for repeated measures will be used for statistical analysis, as well as the Hardy-Weinberg equilibrium, considering p <0.05. (AU)