The Association Of UGY1A1Polymorphism With The The Efficacy Of Irinotecan Chemotherapy On Advanced Colorectal Cancer And Its Adverse Reaction

Objective:Uridine-diphospho glucuronosyl transferase1A1(UGT1A1) plays an important role in metabolism of irinotecan as enzyme, the gene polymorphism significantly affectes the activity of UGT1A1. The association of UGT1A1*28polymorphism with the chemotherapy efficacy and toxicity of irinotecan on patients with metastatic colorectal carcinoma (MCRC) were observed in this paper.Methods:Randomly selected36patients with advanced colorectal cancer patients enrolled in the Second Xiangya hospital of Central South University and Hunan province tumor hospital from from September2011to April2013; all patients which had appreciable metastatic focus were confirmed by pathology. All treatments were based on the consent of patients and family members. But the genotype of two patients cannot be obtained, and the assessment of one patient cannot be gained, one patient accepted another treatment before the end of study. Accordingly,32patients complete the study at last. Thereinto, there were20patients with colon cancer and12patients with rectum tumour. The whole blood samples were drawn from all patients to extract the DNA and analysis genotype by PCR UGT1A1*28and UGT1A1*6gene promoter. All toxicity should be recorded detailedly (refer to the NCI-CTC2.0standard) to appraise the security of irinotecan. Chemotherapy efficacy should be appraised based on the RECIST standard. At last, the relativity between UGT1A1phenotype and chemotherapy toxicity and efficacy were analysed.Results:(1) In this study, patients with UGT1A1*28gene promoter TA6/6is the most common (21eases), accounted for65.6%, followed by geno type of TA6/7type (9cases), accounting for28.1%, patients with UGT1A1gene promoter TA7/7is the least, only2cases, accounted for6.3%. UGT1A1*6gene promoter consists of G/G, G/A and A/A, patients with G/G is23cases (71.9%), with G/A is8cases (25.0%), with A/A is1case (3.1%).(2) All patients after chemotherapy with CPT-11joint5FU/CF; the major toxicities were delayed diarrhea, leucocytopenia and neutropenia, the rate of them in Grade3-4were25.0%,31.3%and15.62%.(3) Delayed diarrhea has no significant correlation with age, chemotherapy background, ECOG score, and original site (P>0.05), The serious risk of delayed diarrhea on patients with UGT1A1gene promoter phenotype TA6/7and TA7/7type is four times than with type of TA6/6(OR=4.606).(4) non--wild genotype of UGT1A1*28(TA6/TA7orTA7/TA7) can increase the risk of diarrhea in Grade3-4in patients more than the others(P<0.05), UGT1A1*6patients with mutant (G/A or A/A-type) occurred neutropenia in Grade3-4incidence is much higher than in patients with wild genotype (G/G)(P<0.05), patients with UGT1A1mutant (promoter and first exon either mutations)(SV-type and DV type) occurred neutrophil in Grade3-4is much higher than double wild the (DW type), the difference was significant (P<0.05).(5) There is no relationship between UGT1A1gene of promoter or The first exon polymorphism and chemotherapy efficacy(Objective response rate and disease control rate) in Patients with advanced colorectal cancerConclusion:UGT1A1promoter type TA6/6, TA6/7, G/G and G/A is more common in patients with colorectal tumour. In this study, the main dose-limiting toxicity of irinotecan consists of leucocytopenia, neutropenia and delayed diarrhea. There is a relationship between UGT1A1gene promoter polymorphism and toxicity consisting of neutropenia and delayed diarrhea. UGT1A1gene promoter TA6/7and TA7/7genotype increase significantly the risk of severe diarrhea, when UGT1A1*6A/A and G/A increase significantly the risk of severe neutropenia. There is no relationship between UGT1A1gene of promoter or The first exon polymorphism and chemotherapy efficacy (Objective response rate and disease control rate) in Patients with advanced colorectal cancer...