Study on the Relationship between UGT1A1 Gene Polymorphisms and Irinotecan-induced ADR / 中国药房

ABSTRACT

OBJECTIVE:To study the correlation of UGT1A1 gene polymorphisms with the incidence and severity of irinote-can-associated ADR in the patients with irinotecan-based chemotherapy. METHODS:56 patients with advanced gastroenteric tumor and small cell lung carcinoma were selected from our hospital and treated with irinotecan-based chemotherapy. The occurrence of ADR was observed during chemotherapy. Gene DNA were collected from peripheral blood sample,and UGT1A1 gene polymor-phisms was determined. The relationship of genotypes with ADR was analyzed. RESULTS:TA sequence of UGT1A1*28 genetic lo-cus was as followswild-type genotype TA6/6(42 cases,75.0%),heterozygous mutation-type TA6/7(13 cases,23.2%)and ho-mozygous mutation-type TA7/7(1 cases,1.8%);that of UGT1A1*6 genetic locus was as followswild-type genotype(44 cases, 78.6%),heterozygous mutation-type(10 cases,17.9%)and homozygous mutation-type(2 cases,3.6%). In UGT1A1*28 genetic locus,6 wild-type genotype patients and 3 mutation-type patients suffered from Ⅲ degree or above hypoleukemia and/or neutrope-nia (14.3% vs. 21.4%,P>0.01),among which only one homozygous mutation-type patient suffered from hypoleukemia and/or neutropenia(100%);6 wild-type genotype patients and 2 mutation-type patients suffered from Ⅲ degree or above diarrhea(14.3%vs. 14.3%,P>0.01),among which only one homozygous mutation-type patient suffered from Ⅲ degree or above diarrhea (100%). In UGT1A1*6 genetic locus,3 wild-type genotype patients and 8 mutation-type patients suffered from Ⅲ degree or above neutropenia (6.8% vs. 66.6%,P<0.01),and 2 wild-type genotype patients and 7 mutation-type patients suffered from Ⅲ degree or above diarrhea(4.5% vs. 58.3%,P<0.01). CONCLUSIONS:Among patients with advanced gastroenteric tumor and small cell lung carcinoma,UGT1A1 gene wild-type gene promoter is most common,followed by heterozygous mutation-type,and homozy-gous mutant rare. For TA7/7 homozygous mutation-type patients,irinotecan-based chemotherapy increase the risk of Ⅲ degree or above hypoleukemia and/or neutropenia and diarrhea. For TA6/7 heterozygotes patients and TA6/6 wild-type patients, irinote-can-based chemotherapy doesn't affect the incidence of Ⅲ degree or above neutropenia and diarrhea. For UGT1A1*6 genetic locus mutation-type patients,irinotecan-based chemotherapy significantly increase the risk of Ⅲ degree or above neutropenia and diar-rhea.