Relationship between UGT1A1*28 and UGT1A1*6 gene polymorphism and adverse reactions of irinotecan-based chemotherapy

Objective To assess the correlation of UGT1A1*28 and UGT1A1*6 gene polymorphism with adverse reactions of irinotecan-based chemotherapy by analyzing the distribution of UGT1A1 gene polymorphism in Chinese people. Methods Peripheral blood samples were taken from 158 malignant tumor patients admitted to our hospital from March 2011 to March 2012.Their UGT1A1*28 and UGT1A1*6 genotypes were detected by direct sequencing. Of the 158 patients, 132 received irinotecan chemotherapy. The adverse reactions to irinotecan chemotherapy were compared in patients with different genotypes. Results Among the 158 patients with UGT1A1*28 gene, wild genotype TA6/6, heterozygotic mutation genotype TA6/7, and homozygotic mutation genotype TA7/7 were detected in 126 (79.7%), 30 (19.0%), and 2 (1.3%) patients, respectively. Among the 64 patients with UGT1A1*6 gene, wild genotype G/G, heterozygotic mutation genotype G/A, and homozygotic mutation genotype A/A were detected in 40 (62.5%), 23 (35.9%), and 1 (1.6%) patients, respectively. The incidence of grades 2-4 delayed diarrhea was lower in patients with wild genotype TA6/6 than in those with wild genotypes TA6/7 and TA7/7 (15.0% vs 34.8% and 50.0%，P=0.000).The incidence of grades 3-4 neutropenia was signi fi cantly lower in patients with wild genotypes TA6/6 and G/G than in those with a heterozygotic or homozygotic mutation genotype or with both heterozygotic and homozygotic mutation genotypes (13.0% vs 22.2% and 100.0%, P=0.004；8.7% vs 25.9% and 66.7%, P=0.045). Conclusion The incidence of adverse reactions to irinotecan chemotherapy is high in patients with UGT1A1*28 and UGT1A1*6 gene mutations. Detection of UGT1A1*28 and UGT1A1*6 genotypes can more accurately predict the adverse reactions to irinotecan chemotherapy than detection of UGT1A1*28 or UGT1A1*6 genotype.