Gene polymorphism and prediction of toxicity to platinum-based chemotherapy in patients with gynecologic cancer.

Abstract

The relationship between single nucleotide polymorphisms (SNPs) at various loci and adverse drug reactions (ADRs) in patients with gynecologic cancer receiving platinum-based chemotherapy (PPCT) remains unexplored. This research aimed to investigate the correlation between SNPs at several loci (e.g., GSTP1 rs1695, MTHFR rs1801133, XPC rs2228001, TP53 rs1042522, and ERCC1 rs3212986) and ADRs in patients with gynecologic cancer receiving PPCT. A total of 244 patients with gynecologic cancer who received first-line PPCT were included in this retrospective study. Blood fluorescence quantitative polymerase chain reaction was used to detect genotypes. Logistic regression, Pearson's Chi-square test, and Fisher's exact test were used to explore the correlations between these SNPs and the occurrence of ADRs. The logistic regression results showed that different genotypes of the five genes had no statistical significance in the overall grade greater than or equal to 3 ADRs. The results of Pearson's Chi-square test showed the same results. On specific adverse reactions, we found that the rs1042522 GG genotype significantly increased the risk of grade greater than or equal to 3 leucopenia compared with the CG and the CC genotypes (p = 0.002). The rs1695 AG genotype showed higher correlation for grade greater than or equal to 3 neutropenia (p = 0.020). The rs2228001 CC genotype also had a higher risk for grade greater than or equal to 3 neutropenia (p = 0.003). This study found that whereas the overall grade greater than or equal to 3 adverse reactions in patients with gynecologic cancer receiving PPCT were not associated with SNPs, specific SNPs (rs1042522 GG, rs1695 AG, and rs2228001 CC) were linked to higher risks of leucopenia and neutropenia, indicating their potential as predictors of hematotoxicity in PPCT-treated patients with gynecologic cancer.