OBJECTIVE: To assess the polymorphism of UGT1A gene in Chinese, and to investigate the correlation between UGT1A polymorphism and irinotecan toxicity in colorectal cancer patients. METHODS: 70 patients with advanced colorectal cancer were treated with irinotecan and 5-fluorouracil. Polymorphism analysis was performed in all those patients and 100 healthy subjects. Genomic DNA was extracted from peripheral blood and genotyped using polymerase chain reaction and direct sequencing. RESULTS: 14 patients exhibiting grade 3 - 4 neutropenia (20.0%), 16 patients experienced grade 2 - 4 diarrhea (22.9%), including only 4 patients with grade 3 - 4 diarrhea (5.7%). Compared with TA6/7 and TA7/7, UGT1 A1 * 28 wild genotype TA6/6 was significantly associated with reduced toxicity (42.1% vs. 15.7%, P = 0.027). There was no significant difference in the distribution of UGT1A genotypes between colorectal cancer patients and healthy subjects. CONCLUSION: Chinese patients exhibit less irinotecan-related diarrhea due to higher frequence of UGT1A A1 * 28 wild genotype TA6/6.
OBJECTIVE: To assess the polymorphism of UGT1A gene in Chinese, and to investigate the correlation between UGT1A polymorphism and irinotecantoxicity in colorectal cancerpatients. METHODS: 70 patients with advanced colorectal cancer were treated with irinotecan and 5-fluorouracil. Polymorphism analysis was performed in all those patients and 100 healthy subjects. Genomic DNA was extracted from peripheral blood and genotyped using polymerase chain reaction and direct sequencing. RESULTS: 14 patients exhibiting grade 3 - 4 neutropenia (20.0%), 16 patients experienced grade 2 - 4 diarrhea (22.9%), including only 4 patients with grade 3 - 4 diarrhea (5.7%). Compared with TA6/7 and TA7/7, UGT1 A1 * 28 wild genotype TA6/6 was significantly associated with reduced toxicity (42.1% vs. 15.7%, P = 0.027). There was no significant difference in the distribution of UGT1A genotypes between colorectal cancerpatients and healthy subjects. CONCLUSION: Chinese patients exhibit less irinotecan-related diarrhea due to higher frequence of UGT1A A1 * 28 wild genotype TA6/6.