The Relationship Between The Efifcacy And Adverse Events Of Irinotecanbased Chemotherapy And UGT1A1Gene Polymorphism

Objective:Cancer is a higher incidence of chronic diseases, especially gastrointestinal tumorincidence and mortality rates in the forefront of all malignant tumors.Gastrointestinaltumors with higher invasiveness, most patients prone to recurrence or metastasis aftersurgery,even when the discovery of some patients with advanced stage.In the pastperiod of time, one of the important progress of clinical research is to establish thevalue of chemotherapy in patients with advanced gastrointestinal malignancies.Compared with (Best supportive care with best supportive care, BSC),chemotherapyto help prolong survival and improve quality of life. Irinotecan combined withfluorouracil program is a classic program of advanced gastrointestinal tumors.However, the clinical application of the program is limited by adverse reactions, andindividual differences are obvious. In recent years, many scholars are committed tostudy predictors of irinotecan adverse reactions in order to improve the safety andefficacy of irinotecan. The research focused mainly on irinotecan active product, themain metabolizing enzyme uridine diphosphate glucuronic acid transferase1Al(uridine-diphosphoglucuronosyltransferase1A1, the UGT1A1), the enzyme activity ofits gene polymorphism can change. this enzyme polymorphism may be associated withthe lack of diarrhea and granulocyte-related. The results of domestic and foreignvarious studies concluded that different. This study aimed at studying the UGT1A1gene polymorphism, in combination with other clinical and pathologicalfeatures,analyzing the relationship between Irinotecan drug chemotherapy side effects,efficiency and the UGT1A1gene polymorphism.Providing the basis for the clinical development of individualized treatment programs.Methods:Randomly selected from the Anhui Provincial Hospital69patients with advancedgastrointestinal cancer patients enrolled in Augest2010to2011in September, allpatients were confirmed by pathology, and to assess metastases.One case can notsuccessfully obtain the genotype.One case can not be required to assess efficacy.A casefailed to be followed up and unable to complete the regimen.Therefore,66patientsultimately required to complete the study20cases of advanced gastric cancer,46casesof intestinal tumors, extract the patient’s whole blood samples, extraction of DNA inwhole blood, Amplified by PCR UGT1A1gene promoter and analysis ofgenotype.Observing the group case, record and evaluate the most severe toxicity (referto the NCI-CTC2.0standard) and three weeks after2cycles of chemotherapy efficacy(refer to RECIST criteria) in clinical patients with2cycles of chemotherapy.With SPSSl3.0statistical software to analyze the correlation of phenotype withchemotherapy toxicity and efficacy. Statistical methods included chi-square test, exacttest and logistic regression analysis.Results:1． In this study， patients with UGT1A1gene promoter TA6/6is the mostcommon(52cases),acounted for78.8%, followed by geno type of TA6/7type(14cases), accounting for21.2%, no mutation homozygotes (TA7/7).2. This group of patients after chemotherapy with CPT-11Joint5FU, the majortoxicities were delayed diarrhea and neutropenia, its were13.7%and24.2%.3. The dependent in fluential factors of delayed diarrhea is the gennotyes ofUGT1A1genepromoter(P=0.031).UGT1Al gene promoter phenotype TA6/7typeof patients with serious risk of delayed diarrhea is more than four times the TA6/ 6patients (OR=4.606).Delayed diarrhea has no significant correlation with age,chemotherapy background, ECOG score,and original site (P>0.05).4. In this study, patients treated with CPT-11Joint5-FU, including10cases ofgastric cancer, response rate (PR+CR) was20%.56cases of Intestinal tumors,response rate (PR+CR) was21.4%.Concolutions:1. UGTlA1gene promoter polymorphism is the influencing factor of delayeddiarrhea, different UGT1A1genotypes with risk of delayed diarrhea weresignificantly different in patients. UGT1A1gene promoter TA6/7genotypepatients, significantly increased the risk of delayed diarrhea than TA6/6genotype,but no marked increase in grade3or4diarrhea and neutropenia wasobserved.2. UGT1A1promoter type TA6/6is more common in patients withgastrointestinaltumors in china，but type TA7/7is rare．3. In this study, neutropenia and delayed diarrhea are the main dose-limiting toxicityof irinotecan.