MDM2 rs2279744 and TP53 rs1042522 Polymorphisms Associated with Etoposide- and Cisplatin-Induced Grade III/IV Neutropenia in Chinese Extensive-Stage Small-Cell Lung Cancer Patients

Abstract

Background/Aims: Etoposide and cisplatin (EP) chemotherapy is the most frequently used regimen in extensive-stage small-cell lung cancer (SCLC) patients, although the side effects (e.g., neutropenia) are high. This study investigates the association of the MDM2 rs2279744 and TP53 rs1042522 single-nucleotide polymorphisms (SNPs) with EP-induced grade III/IV neutropenia and with response to EP in extensive-stage SCLC patients. Methods: Blood samples from 119 extensive-stage SCLC patients were subjected to genotyping of these 2 SNPs, using the allele-specific matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry for determining the association with neutropenia in the patients. Results: The data showed that patients carrying the MDM2 rs2279744-GG genotype were associated with a lower incidence of grade III/IV neutropenia in the recessive and additive models, while the TP53 rs1042522-CC genotype was associated with a higher incidence in the recessive model. Furthermore, the combination of the MDM2 rs2279744-TT+TG and the TP53 rs1042522-CC genotype was associated with a significantly higher incidence of grade III/IV neutropenia. And the combination of the MDM2 rs2279744-GG and the TP53 rs1042522-GG+GC genotype was associated with the lowest incidence of grade III/IV neutropenia. Conclusions: MDM2 rs2279744 and TP53 rs1042522 SNPs were associated with EP-induced high-grade neutropenia in extensive-stage SCLC patients. Further studies are needed to investigate the underlying mechanisms.