UGT1A1 6/28 polymorphisms could predict irinotecan-induced severe neutropenia not diarrhea in Chinese colorectal cancer patients.

The aim of this study was to investigate the associations between UDP-glucuronosyltransferase (UGT) 1A1 polymorphisms and irinotecan-induced toxicities in Chinese advanced colorectal cancer patients. The genotypes of UGT1A1 6 and UGT1A1 28 were analyzed by PCR amplification and Sanger sequencing in 276 advanced colorectal 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 and UGT1A1 28 variants was 35.5 % (GA: 28.6 %; AA: 6.9 %) and 21.0 % (TA6/TA7: 19.9 %; TA7/TA7: 1.1 %) in our cohort, respectively. A total of 16 patients (5.8 %, 16/276) had severe diarrhea and 56 patients (20.3 %, 56/276) had severe neutropenia. Neither UGT1A1 6 nor UGT1A1 28 variants were associated with severe diarrhea; however, either UGT1A1 6 (P = 0.001) or UGT1A1 28 (P = 0.029) variants were significantly associated with severe neutropenia. No differences were found between severe toxicities and clinical response in this study. Compared to western countries, Chinese patients had a distinct frequency of UGT1A1 6 or UGT1A1 28 genotypes. Both UGT1A1 6 and UGT1A1 28 variants were closely associated with irinotecan-induced severe neutropenia, but not diarrhea.