| Objective:After cisplatin,carboplatin,Oxaliplatin is third generation Platinum agents,peripheral neurotoxicity is one of the most characteristic side effects of Oxaliplatin and it has very high incidence ? Oxaliplatin-induced peripheral neurotoxicity(Oxaliplatin-induced peripheral neuropathy,OXLIPN)can be characterized by acute toxicity and chronic toxicity.Acute toxic reactions appear during the infusion of Oxaliplatin after the medication for one day or two.Cold stimulation can cause or worsen acute toxicity,but cold stimulus can not trigger chronic toxicity?Chronic toxicity showes a dose-dependent manner?Oxaliplatin Pharmacogenomics research is expected to designe individualized regimens based on a patient's genetic characteristics,on the premise of no serious adverse reaction in patients,but have access to the best effects.Current Genomics studies on OXLIPN drugs was largely limited to Oxaliplatin metabolism-related genes.The genetic variation is not sufficient to fully explain the OXLIPN of individual differences.Few studies about the role of Oxaliplatin target--Voltage-gated sodium ion channels in Pharmacogenomics.People products h Nav1.7 sodium channel SCN9A gene expression plays a particularly important role in OXLIPN,is an important target in OXLIPN Pharmacogenomics studies.By retrieving the Genbank database,find rs3750904?rs6746030?rs12478318three potential change function of SCN9A Exon regions in polymorphic loci.Select this three points as the project site.We intend to analyze the relationship between the three points of potential change and the colorectal cancer patients' Oxaliplatin-induced peripheral neuropathy,for Oxaliplatin in personalized medicine to provide new scientific evidence.Methods:1 ? The first step: Collect around 168 patients' peripheral blood of colorectal cancer who received oxaliplatin-containing chemotherapy regimen in the treatment,extracting DNA,-20 C refrigerator.2?The second step: Conduct a questionnaire survey for chemotherapy patients,collect clinical information.3?The third step: Use the NCI-CTC(National Cancer Institute common toxicity criteria)on Oxaliplatin Chemotherapy specific standards to asse the Oxaliplatin nerve toxicity.4?The four step: Classify the gen type of rs3750904?rs6746030?rs12478318 on the SCN9A5?The last step: Included in the non-genetic factors such as age,gender,body mass index,chemotherapy(FOLFOX and XELOX)and Oxaliplatin cumulative dose and Oxaliplatin infusion speed into the multiple regression equation,analysis relationship of the SCN9A exon gene type,haplotype associated with 0-IV-OXLIPN through the orderly regression Spss17.0 software;Using the adding/multiplying model to analysis gene and non-genetic factors' interactions in 0-?-role OXLIPN.Results:1?Univariate regression analysis results showed that male patients of different sexes ? neurotoxicity of Oxaliplatin ratio is highest.about 42.3%;Grouping of body mass index in patients with a BMI of 18.5 or less level ? neurotoxicity of Oxaliplatin has highest ratio about 60%;Different cumulative dose group of patients,when dose is 1080mg/sqm,incidence of ? nerve toxicity is 58.5%;Genotype rs3750904 base for C/T or C/C 0 nerve toxicity is 64.8%,Genotype rs12478318 bases for G/T 0 nerve toxicity is 71.4%?Various levels of gender,body mass index,Oxaliplatin cumulative dose and Oxaliplatin infusion speed,genotypers3750904,genotype rs12478318,has statistically significant difference,P<0.05?2 ? Multivariate ordinary analysis shows the cumulative dose is a risk factor(OR>1),and as the dose increases the risk of Neurotoxicity factors greater;Slowing infusion speed reduces the risk of neurotoxicity happence.Gene mutations are protective factors(OR<1),neurotoxicity of pations whose genetic mutation of genes rs3750904 and rs12478318 is decreased.Based on the OR values,the greatest factors effected on the severity of neurotoxicity of Oxaliplatin is the mutant gene for type rs3750904(OR 0.008 per cent),followed by the mutant genotype rs12478318(OR 0.125).3?Two-factor interactions analysis results showed that mutant gene rs3750904 in4 ranks of cumulative doses are relevant(OR value 0.0042,0.0005 0.0001,respectively,0.0003).In cumulative doses of 840mg/ ?,mutant gene rs3750904 meaning more protection;Mutation gene rs3750904 collaborative with rs12478318 and the wild-type gene,interaction OR<1.Conclusions:1?Neurotoxicity of Oxaliplatin is a type of dose limits,with the cumulative dose increased the risk of neurotoxicity increased.2 ? SCN9A gene base sequence of polypeptide locus rs3750904 C/C or C/T mutations are less susceptible to neurotoxicity,is a protective factor.3?SCN9A gene base sequence of polypeptide locus rs12478318 G/T mutation is not susceptible to neurotoxicity,as a protective factor.4 ? SCN9A gene base sequence of polypeptide locus rs3750904 C/C or C/C mutations maybe has more protective effect than the base sequence of the rs12478318G/T mutation... |
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