Frequency of UGT1A1*28 gene polymorphism in Chinese gastrointestinal cancer patients and its relationship with irinotecan-related diarrhea.

Abstract

451 Background: The incidence of irinotecan-related adverse events was associated with the polymorphism of uridine diphosphate glucuronosyltransferases (UGTs) gene, and demonstrated as obvious ethnic diversity. The aim of this study is to observe the frequency and severity of various adverse events in Han patients with advanced gastrointestinal cancer who was treated with irinotecan-based therapy. Simultaneously, the relationship between the severe adverse events and UGT1A1 gene promoter polymorphism (UGT1A1*28) was investigated. Methods: A total of 109 patients (65 men and 44 women; median 57 years; range: 34-76 years) with advanced gastrointestinal carcinoma receiving irinotecan-based chemotherapy were enrolled. The adverse events during the course chemotherapy, the pretreatment serum bilirubin level, as well as the time to the Grade 3-4 toxicities occurrence were recorded. Genomic DNA was extracted from the peripheral blood to detect the polymorphism of UGT1A1*28 (TATA box thymine-adenine TA repeats). The relationship between the severity of adverse events and UGT1A1*28 polymorphism was investigated. Results: Of all these 109 enrolled patients, 90 patients were identified with thymine-adenine (TA)6/(TA)6 genotype, 19 patients with the thymine-adenine (TA)6/(TA)7 genotype, and no (TA)7/(TA)7 genotype was found. Forty-six and 12 patients developed grade 3-4 neutropenia, while 8 and 5 patients occurred grade 3-4 diarrhea in (TA)6/(TA)6group and (TA)6/(TA)7 group, respectively. The occurrence of grade 3-4 diarrhea but not neutropenia was closely related with (TA)6/(TA)7 genotype in UGT1A1 promoter region in patients receiving irinotecan-based chemotherapy (P=0.033). Conclusions: The frequency of UGT1A1*28 gene polymorphism in Han patients is 17.4%, which is lower than that reported in western populations. The marked increase in grade 3-4 diarrhea is related with (TA)6/(TA)7 genotype of UGT1A1 in patients receiving irinotecan-based chemotherapy. [Table: see text]