Associations between UGT1A1*6/*28 polymorphisms and irinotecan-induced severe toxicity in Chinese gastric or esophageal cancer patients

Abstract

The aim of this study was to investigate the associations between UDP-glucuronosyltransferase (UGT) 1A1 polymorphisms and irinotecan-induced toxicities in Chinese advanced gastric or esophageal cancer patients. The genotypes of UGT1A1*6 and UGT1A1*28 were analyzed by PCR amplification and Sanger sequencing in 42 gastric and 91 esophageal cancer patients receiving irinotecan-containing chemotherapy. The influences of UGT1A1*6/*28 polymorphisms on severe diarrhea and neutropenia were analyzed. The overall incidence of UGT1A1*6/*28 variants in gastric cancer and esophageal cancer was 38.1 % (GA: 31.0 %; AA: 6.9 %), 28.6 % (TA6/TA7: 26.2 %; TA7/TA7: 2.4 %) and 33.0 % (GA: 28.6 %; AA: 4.4 %), 25.3 % (TA6/TA7: 23.1 %; TA7/TA7: 2.2 %) in our cohort, respectively. A total of 10 patients (gastric cancer: 9.5 %, 4/42; esophageal cancer: 6.6 %, 6/91) had severe diarrhea and 35 patients (gastric cancer: 35.7 %, 15/42; esophageal cancer: 22.0 %, 20/91) had severe neutropenia. Statistic analysis between UGT1A1 genotyping and severe diarrhea was not conducted due to the limited number of patients. For gastric cancer, it seemed that only UGT1A1*6 variant was associated with severe neutropenia (P = 0.042), while among esophageal cancer patients, UGT1A1*6 (P = 0.011) or UGT1A1*28 (P = 0.026) variants were significantly associated with severe neutropenia. UGT1A1*6 variant was closely associated with severe neutropenia both in gastric cancer and in esophageal cancer, but the association between UGT1A1*28 variant and severe neutropenia in gastric and esophageal cancer was not consistent in this study, which would be validated in the future large samples.