UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer

Abstract

Objectives

To investigate the relationship between uridine diphosphate glucoronosyltransferase 1A1 (UGT1A1)*28/*6 and toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer (CRC) in Xinjiang Uygur and Han population.

Methods

A total of 183 patients (Uygur, 114; Han, 69) with advanced CRC who received the irinotecan-based chemotherapy were enrolled in this retrospective analysis. Polymerase chain reaction amplification and direct sequencing method were used for UGT1A1*28 and UGT1A1*6 polymorphism detection. The patients were followed up to analyze the relationship between different genotypes with adverse reactions and the clinical outcome of irinotecan-based chemotherapy.

Results

Significant differences were found in genotype frequencies of UGT1A1*28 and UGT1A1*28/*6 between Uygur and Han (P = 0.02 and P = 0.002). Uygur and Han patients carrying wild UGT1A1*28 and *6 genotypes appeared to have significantly lower diarrhea incidence (I/II and III/IV) than those carrying mutant genotypes (all P < 0.05). In Uygur patients, UGT1A1*28 genotypes were related with objective response rate and disease control rate (P < 0.05). Compared with *1 allele *1/*1, *1 allele *1/*28*1/*28 mutant of UGT1A1*28 was associated with shorter OS in both Uygur and Han ethnicities (all P < 0.05). Compared with double allele variants (DW), single allele variants (SV), and double allele variants (DV) of UGT1A1*28/*6 were associated with shorter overall survival (OS) in Uygur and Han (all P < 0.05). Cox regression analysis revealed factors significantly influencing OS, including UGT1A1*28, UGT1A1*6, combined genotypes and chemotherapy line in Ugyur, and only combined genotypes in Han (all P < 0.05).

Conclusion

UGT1A1 gene polymorphism predicts irinotecan-related adverse reactions in advanced CRC patients of Xinjiang Uygur and Han nationality; UGT1A1 gene polymorphism is correlated with efficacy and prognosis in Uygur nationality, but only related to prognosis in Han nationality in irinotecan-based chemotherapy.

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