Study On The Relationship Between UGT1A1,SLCO1B1 Gene Polymorphism And Irinotecan In The Treatment Of Colorectal Cancer

Objective:Through detecting of UGT1A1*28,UGT1A1*6 and SLCO1B1(388A>G)gene in patients with colorectal cancer(CRC),analyzing the genetic polymorphism distribution.Observe the situation of bone marrow suppression and delayed diarrhea in metastatic colorectal cancer(mCRC)patients receiving irinotecan(CPT-11)chemotherapy analysis UGT1A1*28,UGT1A1*6,SLCO1B1(388 A>G)gene polymorphism and CPT-11 adverse reaction of chemotherapy,as to provide theoretical basis for guiding clinical individualized medication.Methods:Collected patients were diagnosed with CRC in pathology from November 2016 to December 2017 in Yunnan Cancer Hospital.After informed consent,UGTIA1*28 gene was detected by PCR capillary electrophoresis,UGT1A1*6 and SLCO1B1(388A>G)gene was detected by digital fluorescent molecular hybridization,collected patients clinical data to the patient's genotype distribution of genetic polymorphism analysis.We observed the situation of bone marrow suppression and delayed diarrhea with mCRC patients receiving CPT-11 chemotherapy,according to NCI-CTC v4.0 evaluation of adverse reaction of chemotherapy,analyze the relationship between UGT1A1*28,UGT1A1*6,SLCO1B1(388A>G)gene polymorphisms and CPT-11 chemotherapy adverse reactions.Results:1?A total of 122 cases of CRC patients with pathological diagnosis were collected,including 63 routine UGT1A1*28 gene detection and 59 cases of UGT1Al1*6 and SLCO1B1(388A>G)gene detection.The distribution of gene locus was as follow:the wild type TA6/6,heterozygous mutant TA6/7,homozygous mutant TA7/7 of UGT1A1*28 gene accounted respectively for 79.4%(n=50),17.4%(n=11),3.2%(n=2);the wild type G/G,heterozygous mutant G/A and homozygous mutant A/A of UGT1A1*6 gene accounted respectively for 55.9%(n=33),35.6%(n=21)and 8.5%(n=5);the wild type A/A,heterozygous mutant A/G and homozygous mutant G/G of SLCO1B1(388A>G)gene account respectively for 13.6%(n=8),27.1%(n=16)and 59.3%(n=35);in the joint detection of UGT1A1*6 and SLCO1B1(388A>G),the bigene wild,single gene mutation and double gene mutation accounted for 8.5%(n=5),52.5%(n=31)and 39.0%(n=23).2.72 mCRC patients patients received CPT-11 chemotherapy,the patients who developed 0-? degree and ?-? degree delayed diarrhea after chemotherapy were 95.8%(n=69)and 4.2%(n=3)respectively.Patients with bone marrow suppression of 0-? degree and ?-? degree were 93.1%(n=67)and 6.9%(n=5)respectively.3?The mutation of UGT1A1*28 was associated with decreased leucocyte and delayed diarrhea after chemotherapy of CPT-11(P=0.037,P=0.037).4?UGT1A1*6,SLCO1B1(388A>G)gene polymorphisms and CPT-11 chemotherapy adverse reactions were not statistically significant(P>0.05).The joint detection of UGT1A1*6 and SLCO1B1(388A>G)and CPT-11 chemotherapy had no statistical significance(P>0.05).5?CPT-11 chemotherapy had no significant difference in age,sex,ethnicity,ECOG score and tumor location(P>0.05).Conclusions:1?In this group,patients with wild type of UGT1A1*6 and UGT1A1*28 gene were more mutated,while those of SLCOIB1(388A>G)were less mutant.The mutation frequency of UGT1A1*6 gene was higher than that of UGT1A1*28 gene mutation.2?UGT1A1*28 gene mutation may be mCRC CPT-11 after chemotherapy in patients with leucopenia,late-onset diarrhea predictors of mCRC patients need to accept chemotherapy before including CPT-11 scheme,detecting the gene for prediction and prevention of CPT-11 chemotherapy adverse reactions are clinical significance.3?The genetic polymorphism of UGT1A11*6 and SLCO1B1(388A>G)was not correlated with the adverse reactions of CPT-11 chemotherapy.4?Age,sex,ethnicity,ECOG score and tumor location were not related to adverse effects of CPT-11 chemotherapy.