| Background and purpose:Oxaliplatin is a third-generation platinum anti-tumor drug and is one of the commonly used chemotherapy drugs for colon cancer.Compared with the first and second-generation platinum drugs,it has the advantages of relatively lighter gastrointestinal reactions and mild bone marrow suppression.However,its peripheral neurotoxicity is stronger than the previous two generations of platinum.Oxaliplatin has two types of neurotoxicity,acute and chronic,and its incidence is about 90%.Its neurotoxic effects cause psychological and physical harm to patients,affect the quality of life of patients,and limit clinical applications.At present,there are few genomics researches on the peripheral neurotoxicity of oxaliplatin,which is not enough to explain the individualized differences in peripheral neurotoxicity of oxaliplatin.Therefore,the genetic research on the peripheral neurotoxicity caused by oxaliplatin,It will be able to individualize the medication according to the patient’s unique genetic characteristics,so that the patient can receive the best treatment plan.At present,the significance of genetic variation of related genes in OXLIPN has been confirmed in many research experiments.Through previous research reports,we found that the voltage-gated sodium channel-the human SCN10 A gene expression product h Nav1.8 sodium channel is mainly detected in DRG,because OXLIPN is often caused or aggravated by cold stimulation,and SCN10 A is associated with neuropathic pain,Cold pain and so on are closely related.We speculate that the human SCN10A/h Nav1.8 sodium channel may have important significance in OXLIPN,and it is an important target in OXLIPN pharmacogenomics research.We searched the Genbank database and found that the five loci rs77049337,rs74717885,rs12632942,rs6795970,and rs57326399 of the human SCN10 A gene have potential genetic variation functions.Therefore,these five loci were selected as the research sites of the project.Analyze the correlation between rs77049337,rs74717885,rs12632942,rs6795970,rs57326399 and the peripheral neurotoxicity of oxaliplatin in the colorectal cancer population with potential functional changes in the exon region of the human SCN10 A gene,which is oxali The personalized medication of platinum provides a new scientific basis.Method:The peripheral blood of 117 patients with colorectal cancer who received oxaliplatin-containing chemotherapy were collected,and DNA was extracted and genotyped.Conduct a questionnaire survey on the enrolled patients,collect the necessary clinical data,and use the general NCI-CTC(National Cancer Institute Common Toxicity Criteria)specific criteria for oxaliplatin to evaluate the peripheral neurotoxicity of oxaliplatin in the enrolled patients.Then SPSS 25.0 statistical software was used to analyze the correlation between genetic polymorphism and peripheral neurotoxicity through ordered regression analysis.Result:The results of one-way analysis of variance and Kruskal-Wallis H test indicate differences in grade composition of different genders,cumulative dose of oxaliplatin,oxaliplatin infusion rate,genotype rs rs74717885,genotype rs12632942,genotype rs6795970,and genotype rs57326399 There is statistical significance(P<0.05).The results of multivariate ordered regression analysis showed that the cumulative dose of oxaliplatin,the genotype rs12632942 mutation was a risk factor for oxaliplatin peripheral neurotoxicity(OR>1),and the genotype rs6795970 mutation was the protection of oxaliplatin peripheral neurotoxicity Factor(OR<1).Two-factor interaction analysis results show that the mutant gene rs12632942 is related to the three levels of oxaliplatin cumulative doses(OR values are all greater than 1);the mutant gene rs12632942 interacts with the mutant gene rs6795970 and the wild-type gene rs6795970 effect(OR>1).Conclusion:The peripheral neurotoxicity of oxaliplatin belongs to the dose-limiting type.As the cumulative dose increases,the risk of peripheral neurotoxicity in patients increases.Colorectal cancer patients with mutations in the rs12632942 polymorphic site of the SCN10 A gene are more likely to have peripheral neurotoxicity of oxaliplatin.Colorectal cancer patients with mutations in the polymorphic site rs6795970 are less likely to develop peripheral neurotoxicity,and the risk effect of mutations in the gene rs12632942 is stronger than The protective effect of mutations in gene rs6795970. |
PDF Full Text Request