Clinical implications of drug-metabolizing genes CYP3A4 and GSTP1 single nucleotide polymorphisms in oral cancer patients undergoing induction chemotherapy.

Abstract

95 Background: Despite well-established induction chemotherapeutics for advanced-stage oral cavity cancer (OCC), there are no reliable markers to detect drug-induced toxicity and clinical efficacy. The presence of genetic polymorphisms can cause certain enzymes to behave differently in various populations, which can lead to varied outcomes. Thus, we analyzed the effect of metabolizing (CYP3A4) and detoxifying (GSTP1) genes involved in taxane/platinum/5-fluorouracil (TPF) or paclitaxel/carboplatin (PC) metabolism and their clinical outcomes in OCC patients. Methods: The current study included 121 OCC patients who received fixed dose of TPF or PC-based chemotherapy. PCR-RFLP was used to assess the polymorphism of the metabolising gene. SNPs were tested for toxicity and progression-free survival. Results: The grade ≥2 patients (47.9%) having higher fever (33.8%) and vomiting (34.7%) as a result of chemotherapy, showed significant association with the gene CYP3A4 (rs2687105) in both the PM and IM genotypes. For PM genotypes, the odd ratio (OR) of CYP3A4 for fever was 2.33E8 (95% CI: 4.702E7-1.154E9, p = 0.000), and for IM genotypes, it was 6.99E8 (95% CI: 1.89E8-2.581E9, p = 0.000). Meanwhile, the patients with grade ≥2 (58.6%) having anaemia (11.5%) and nausea (32.2%) also found to be significantly associated with GSTP1 (rs749174) in PM genotypes; the odds ratio was (OR: 8; 95%CI:1. 1001-63.963; p=0.05) and (OR: 2.667; 95%CI:1.043-6.815; p=0.04). Moreover, patients with these SNPs showing poor survival rate, however there was no significant association observed between the genotypes of each SNPs with progression-free survival (PFS). Conclusions: In conclusion, our data showed that the rs2687105 in CYP3A4 and the rs749174 in GSTP1 were associated with adverse events of TPF or PC chemotherapeutic regimens among the oral cancer patients. Therefore these genes might be used as predictive markers for minimising the adverse effects caused by chemotherapy and for optimization of drug dose in oral cancer patients.