XRCC1, ABCB1, CYP3A5 and GSTP1 gene polymorphism associated with platinum-based drugs induced hematotoxicity in Chinese oesophageal cancer patients

Abstract

Background

Hematotoxicity, including severe myelosuppression, is a common adverse drug reaction (ADR) during platinum-based treatment for oesophageal cancer (EC).

Purpose

The aim of this study was to identify single-nucleotide polymorphisms (SNPs) associated with platinum-induced hematotoxicity in patients with EC, as the relationship between SNPs and this ADR is incompletely demonstrated.

Methods

A total of 262 patients receiving platinum-based chemotherapy (cisplatin, nedaplatin, carboplatin and oxaliplatin) were enrolled in this study. Ten SNPs in eight genes were genotyped via multiplex polymerase chain reaction and sequenced to evaluate their relationship with severe myelosuppression and its subset of leukopenia and neutropenia.

Results

Multivariate logistic analysis of cisplatin cohort in severe leukopenia group showed an odds ratio (OR) of GG + GA versus AA in ABCB1 rs1045642 was 5.83 (95% confidence interval (CI) 1.63–20.83, p = 0.007, false discovery rate (FDR) = 0.028), while the OR of AA versus AG + GG in rs1128503 was 0.34 (95% CI 0.14–0.86, p = 0.022, FDR = 0.044). In nedaplatin cohort of neutropenia group, the OR of AA versus GG, AA + AG versus GG in GSTP1 rs1695 was 10.34 (95% CI 1.71–62.40, p = 0.011, FDR = 0.040) and 7.48 (95% CI 1.37–40.81, p = 0.020, FDR = 0.040) respectively. XRCC1 rs1799782 GG genotype in nedaplatin cohort of myelosuppression group and CYP3A5 rs776746 CT genotype in nedaplatin cohort of severe leukopenia group and platinum cohorts of all groups appeared to be risk factors with the p values less than 0.05, but FDR values were all greater than 0.05.

Conclusion

This study identified SNPs of XRCC1, ABCB1, CYP3A5 and GSTP1 related to hematotoxicity of platinum-based drugs, thereby providing a novel theoretical basis for the prediction and prevention of ADRs in platinum-based chemotherapy.