Abstract: Objective To investigate the relationship between the single nucleotide polymorphisms（SNPs） of DNA methyl transferase 3b（DNMT3b） gene and the efficacy of FOLFOX4 regimen in patients with advanced colorectal cancer. Methods The SNP predictive software was used to screen 4 target SNPs（rs6119954， rs4911107， rs4911259， rs8118663） and 2 SNPs（rs1569686， rs2424913） in the promoter region in the HapMap database of DNMT3b gene in Chinese Han population. The distribution of SNPs in peripheral blood DNA of 178 patients with advanced colorectal cancer were detected by direct sequencing. RECIST 11 standard was used to evaluate the short term efficacy of patients receiving FOLFOX regimen after 4 cycles of chemotherapy. The patients were divided into effective group（CR+PR） and ineffective group（SD+PD）. We analyzed different chemotherapy effects and clinical pathological parameters（age， sex， location， tumor size， pathological type， clinical stage and differentiation degree） as well as the relationship between the SNPs locus genotype and allele.
ResultsThere was no significant difference between genotype distribution and predictive value of DNMT3b rs6119954, rs1569686， rs4911107， rs4911259， rs8118663 and rs2424913 in 178 patients with advanced colorectal cancer（P>0.05）. After 4 cycles of chemotherapy， there were 4 cases of CR， 45 cases of PR， 88 cases of SD and 41 cases of PD and then the patients were divided into effective group（n=49） and ineffective group（n=129）. The effect of FOLFOX4 chemotherapy was not related to age， sex， location， tumor size and pathological type， but was related to degree of differentiation（P<0.05）. In rs6119954 and rs2424913， the effective rate of chemotherapy was low， and the risk of ineffective chemotherapy was increased with statistical significance difference（P<0.05）. The distribution of the remaining SNPs loci was not related to the efficacy and the risk of invalid efficacy（P>0.05）. ConclusionDNMT3b rs6119954 and rs2424913 were associated with the efficacy of FOLFOX4 in patients with advanced colorectal cancer. The patients carrying rs6119954 A or rs2424913 T allele have a higher risk invalid efficacy of FOLFOX4 regimen，which has a certain value to predict the efficacy of FOLFOX4 regimen for patients with advanced colorectal cancer.