Title : Association of SPARC and CYP3A5 polymorphisms with peripheral neuropathy induced by nab-paclitaxel in chinese cancer patients
Objective: Genetic polymorphisms of drug metabolic enzymes, transporters and target receptors may account for the interindividual variability of unpredictable peripheral neuropathy induced by nab-paclitaxel. This study aims to identify the biomarkers for peripheral neuropathy induced by nab-paclitaxel in Chinese cancer patients.
Methods: A total of 92 Chinese Han cancer patients were included in the study. Twelve single nucleotide polymorphisms (SNPs) in SPARC, CYP1B1, CYP2C8, CYP3A5, MAPT and TUBB2A were genotyped using the SNAPshot technique. Peripheral neuropathy induced by nab-paclitaxel during the treatment was evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) version 4.03. The effects of genetic variants on peripheral neuropathy induced by nab-paclitaxel were assessed.
Results: Patients who carried the SPARC rs1059829 or rs1053411 mutant alleles had higher risks for grade ≥2 peripheral neuropathy induced by nab-paclitaxel (rs1059829 A allele: odds ratio [OR] = 2.072, 95% confidence interval [CI] = 1.120–3.833, P = 0.0194; rs1053411 C allele: OR = 1.939, 95% CI = 1.042–3.607, P = 0.0353). We also found a significant association between the CYP3A5 rs776746 mutant allele and a lower risk for grade ≥2 peripheral neuropathy (OR = 0.5013, 95% CI = 0.2623–0.9581, P = 0.0352). However, when we considered the Bonferroni correction, the associations between these three SNPs and grade ≥2 peripheral neuropathy were not significant. No association between other genotypes and grade ≥2 peripheral neuropathy was found in this study (P > 0.05).
Conclusions: Several polymorphisms from genes encoding metabolic enzymes and transporters of nab-paclitaxel may be involved in peripheral neuropathy in Chinese cancer patients.