Purpose: Digestive tract cancer patients treated with oxaliplatin are often associated with the development of peripheral neuropathy. The aim of the present study is to identify the influence of single-nucleotide polymorphisms (SNPs) in genes involved in oxaliplatin metabolism, cell cycle control, detoxification or excretion pathways with the development of oxaliplatin-induced acute peripheral neuropathy (acute OXAIPN) and its severity among digestive tract cancer patients treated with oxaliplatin-based chemotherapy.
Patients and methods: A total of 228 digestive tract cancer patients undergoing with the oxaliplatin-based chemotherapy between November 2014 and December 2016 were included in the current study. Genomic DNA was extracted from peripheral blood by standard phenol-chloroform method. Genotyping of five SNPs in four genes [GSTP1 (rs1965), ABCG2 (rs3114018), CCNH (rs2230641, rs3093816), AGXT (rs4426527)] was carried out by Real-Time TaqMan SNP genotyping assay.
Results: We found that the two genetic variants rs2230641 and rs3093816 in cyclin H (CCNH) gene were significantly associated with both the incidence and severity of acute OXAIPN. For CCNH-rs2230641 (AA vs AG+GG; dominant model) Incidence: OR 2.62, 95% CI 1.44-4.75, p = 0.001, severity; OR 4.64, 95% CI 1.58-13.62, p = 0.002. For CCNH-rs3093816 (AA vs AG+GG; dominant model); incidence: OR 3.43, 95% CI 1.57-7.50, p = 0.001; severity: OR 2.36, 95% CI 1.05-5.30, p = 0.033.
Conclusions: The results of the present study found significant association between CCNH polymorphisms and acute OXAIPN development. However, further studies are warranted from independent groups to validate our study results.
Keywords: Cyclin H; Digestive tract cancer; Oxaliplatin; Peripheral neuropathy; Single-nucleotide polymorphisms.