The Association Analysis Of UGT1A Polymorphisms And Toxicity/Effect Of Irinotecan

CPT-11is widely used in treatment of intestinal cancer, gastric cancer, esophageal cancer, extensive small-cell lung cancer and some other solid tumors since1990s. UGTIA polymorphisms have been a hot area of research on toxicity/effect of Irinotecan as the important role in metabolism process of Irinotecan.34gastrointestinal cancer patients, received FOLFIRI or XELIRI, were enrolled onto this study. We found that the rate of diarrhea and neutropenia, which is the major toxic effects, was significantly less than reported in European and American people. In the analysis of UGT1A1/7/9polymorphisms and neutropenia in cycle1, five significant loci had been detected. Along with these mutational sites, the risk of neutropenia when treated with Irinotecan-based chemotherapy in mCRC patients increased by6.667to9.444times. Using Haploview software to predict the phenotype, the results showed that haplotypes were more significant than alleles. Bl-2haplotype could predict neutropenia quite well. We have detected four new variations, one in each5’un-translated region in the UGT1A7and UGT1A9. The other two missense mutations, H203L and L255Q, have been detected in exonl in the UGT1A1.To improve the safety and effect of treatment in different population and individual and realize individualized medication, we want to detect new alleles that affect the functionality of UGTIA, and develop predictive models of toxicity/effect of Irinotecan in Chinese patients in this study.