The Correlation Of Individual Response Differences Between The UGT1A1 Gene Polymorphism Of Guangxi Zhuang Metastatic Colorectal Cancer Patients With Irinotecan Treatment

Objective:Analyse the distribution of Uridine diphosphateglucuronyl transferase 1A1(UGT1A1) gene polymorphism of Guangxi Zhuang metastatic colorectal cancer(mCRC) patients. Exploring the Correlation between UGTIAI gene polymorphism and irinotecan common toxicity,efficacy.Method:Collecting the peripheral blood samples of patients who newly diagnosed metastatic colorectal cancer in the Fourth Affiliated Hospital of Guangxi Medical University from May 01,2014 to March 01,2015. Using pyrosequencing method to detect the UGT1A1* 28 and UGT1A1* 6 polymorphisms. After first-line treatment with FOLFIRI, assessing the degree of toxicity according to NCI-CTC4.0 version. Every 2 cycles of chemotherapy review and evaluate the short-term efficacy. Follow-up to March 01,2016 and to assess median progression-free survival (mPFS)Results:86 patients enrolled were detected both UGT1 Al* 28 and UGT1A1* 6 gene. To UGT1A1*28 gene,60 cases(69.8%)were identified with wild genotype(TA6/6),26 cases(30.2%)were heterozygous (TA6/7), homozygous genotype(TA7/7) was not found; To UGT1A1*6 gene,66 cases(76.7%)were wild genotype(G/G),18 cases(20.9%)were heterozygous(G/A), and 2 case(2.3%)was homozygous genotype(A/A). After chemotherapy with FOLFIRI, Patients with UGT1A1*28 TA6/7 genotype had increased risk of grade 3 and 4 diarrhea than case with TA6/6 genotype(30.8%vs 11.7%, P=0.044). While UGT1A1*28 TA6/7 genotype had not increased the risk of grade 3-4 neutropenia(34.6%vs 15.0%, P=0.112).Patients with UGT1A1*6 G/A+A/A genotype had increased risk of grade 3-4 diarrhea than case with G/G genotype (45%vs 9.1%, P=0.001). G/A+A/A genotype also increased the risk of grade 3-4 neutropenia than case with G/G genotype(40% vs 15.2%, P=0.017). After treatment with FOLFIRI, The Overall response rate(ORR) of UGT1A1* 28 and UGT1A1* 6 wild-type-and mutant patients were 38.3%、42.3%, and 40.9%、45.0% respectively,There was no Significant differences (P=0.729, P=0.745). The mPFS of UGTIAI* 28 TA6/6 genotype and TA6/7 genotype were 7.0 months and 7.4 months, There was no significant difference (P= 0.427). The mPFS of UGTIAI* 6 G/G genotype and G/A+A/A genotype were 6.9 months,7.0 months, There was no significant difference(P= 0.408).Conclusion:1. The distribution of Guangxi Zhuang patients UGTIAI gene polymorphism suggested that UGT1A1*28 heterozygous mutation type was 30.2%, no homozygous mutant;UGT1A1* 6 heterozygous mutation type accounted for 20.9%, homozygous mutant accounted for 2.3%, there are differences between the existing reported of European people and Chinese Han population gene frequency distribution of Chinese Han population.2. The UGT1A1 gene polymorphism could predict the irinotecan related diarrhea and neutropenia. 3.There was no correlation between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.