A Study Of The Correlation Between UGT1A1*28/*6 Gene Polymorphism And The Adverse Reaction And The Efficacy Of Irinotecan-based Chemotherapy In Patients With Advanced Colorectal Cancer

Objective:Irinotecan,CPT-11,has been widely used in the treatment of many solid tumors such as colorectal cancer.But it has huge individual differences in curative effect and adverse reaction of chemotherapy because of uridine diphosphate glucuronosyl transferases1A1(UGT1A1)polymorphism.The purpose of this study was to definite the relationship between UGT1A1*28 and UGT1A1*6 gene polymorphism and the toxic reaction and efficacy of the irinotecan-based chemotherapy in patients with advanced colorectal cancer with or without liver metastases.Methods:The patients who received irinotecan chemotherapy in The Affiliated Tumor Hospital of Guangxi Medical University from October 2015 to December 2016,would be detected UGT1A1*28 gene and UGT1A1*6polymorphism.Record hematologic toxicity and gastrointestinal adverse reactions of patients during chemotherapy.Record efficacy of the irinotecan chemotherapy every 2 to 4 cycles of chemotherapy.Results: 76 case tumor patients,male 49 cases,women 27 cases,acceptedFOLFIRI regimen in 55 cases,accepted raltitrexed plus Irinotecan regimen in21 cases;age was 16~79 years,median age was 53 years.1.UGT1A1*28 geneIn this study,84.21%(64 persons)were identified with TA6/TA6 genotype,14.47%(11 persons)with TA6/TA7 genotype,1.32%(1 person)with TA7/TA7 genotype.DCR/grade III-IV leucopenia/hemoglobin reduce/thrombocytopenia/diarrhea did not present statistically difference in patients with advanced colorectal cancer with or without liver metastases and UGT1A1*28 gene polymorphism.2.UGT1A1*6 geneIn this study,86.84%(66 persons)patients carry UGT1A1*6 wild type G/G,11.84%(9 persons)carry heterozygous G/A,and 1.32%(1 person)carry hoinozygous A/A.The UGT1A1*6 gene mutant type increased the risk of grade III-IV diarrhea(P=0.036,OR=15.032),and couldn't be affected by liver metastases.DCR/grade III-IV leukopenia/Hemoglobin reduce/thrombocytopenia did not present statistically difference in patients with advanced colorectal cancer with or without liver metastases and UGT1A1*6 gene polymorphism.3.UGT1A1*28 and *6 double geneAccording to numbers of mutations.Double wild type of UGT1A1*28 and UGT1A1*6(DW)is 72.36%(55 persons);Single variant type(SV)is 26.32%(20 persons);Double variant type(DV)is 1.32%(1 person).DCR/grade III-IV leukopenia/ hemoglobin reduce/thrombocytopenia did not present statistically difference in patients with advanced colorectal cancer with or without liver metastases and UGT1A1 double gene.Conclusion:1.The study shows that in UGT1A1*28 genes,TA6/6 genotype is the most common and the second is TA6/7 genotype.TA7/7 genotype is theleast common one.In UGT1A1*6 genes,wild type G/G is the most common and the second is heterozygous G/A.Hoinozygous A/A is the least common one.According to the number of UGT1A1*28 and UGT1A1*6.Double wild type of UGT1A1*28 and *6 is the most common and the second is Single variant type.Double variant type is the least common one.2.The rate of III-IV diarrhea happens in patients with UGT1A1 *6 gene mutant type,which is higher than wild type,and couldn't be affected by liver metastases.3.There is no relation between colorectal cancer with or without liver metastases/UGT1A1*28/UGT1A1*6 polymorphism and the efficacy of the irinotecan.