Study Of The Influence Caused By UGT1A1*6 And *28 Gene Polymorphism In Toxicity And Efficacy Of Irinotecan

Objective: Irinotecan is an important chemotherapy drug in solid tumors,but it has large individual differences in Chemotherapy toxicity because of UridineDiphosphoglucuronosyltransferase1 A polymorphism. This Study is to know the relationships between UGT1A1 polymorphism which is genotyped by gene chip(Shanghai Bio) and efficacy or side effects after using irinotecan; and to know the distribution of UGT1A1 polymorphism in Jiang Xi region.Methods: Collect the data and blood of patients who using irinotecan as chemotherapy drug during October 2013 to December 2014 in the First Affiliated Hospital of Nanchang University, including 106 person at last. Follow-up the patients regularly and records of patients during chemotherapy routine blood and adverse reactions, we determined the genetypes of UGT1A1*6 and UGT1A1*28 by Gene Chip which is researched by Bio Company; By analyzing the differences on adverse reaction and short-term effect of different genetypes, discuss on hematology indexes of WBC,NEU,PLT,HB.Statistical methods include c2test,ANOVA,LSD-t test,factorial design analysis,and Logistic regression analysis, P< 0.05 show statistically significant difference.Results:1. 78.3%(83persons) patients carry UGT1A1 * 6 wild type G/G, 19.18% patients carry Heterozygous G/A, and 1.89% patients carry homozygous;76.42% patients carry UGT1A1 * 28 wild type TA6/TA6, 17.92% Heterozygous TA6/TA7, and homozygous 5.66%; The rate of Double Wild type(DW) is 58.49%,Single Variant type is 37.74%, and Double Variant type is 3.77%. 2.UGT1A1*6 gene mutations may cause blood toxicity, characterized by the WBC,NEU and HB reducing;and 3~4 blood toxicity may be related to UGT1A1*6 variant, may be UGT1A1*28 Variant as well. The risk of blood toxicity may increase when a person carry DW gene. UGT1A1*28 variant may cause diarrhea toxicity; 3.UGT1A1*6 and UGT1A1*28 variant has nothing to do with the recent curative effect.Conclusion:1.The major genetype of UGT1A1*6 and *28 genetype in Jiang Xi region is Double Wild type and the Single Variant; 2.UGT1A1*6 gene variant may cause blood toxicity,especially in the persons who combined with UGT1A1*28 variant; 3.UGT1A1*28 variant may cause diarrhea toxicity;4.The individualized Clinical use of irinotecan should consider comprehensive factor such as the drug dose、UGT1A1*6 and UGT1A1*28 genotypes, patients’ age, KPS score.