UGT1A1 Gene Polymorphism Predicts Irinotecan-Induced Severe Neutropenia and Diarrhea in Chinese Cancer Patients.

BACKGROUND

Irinotecan was widely used in colon cancer and lung cancer, etc., and adverse reactions occur some times. The primary aim of this research is to investigate the association between UGT1A1 gene polymorphisms and irinotecan-related adverse effect in Chinese Han population with a novel kind of gene chip technology.

METHODS

UGT1A1*6/*28 gene polymorphisms were detected by PCR and gene chip as well as sequencing. The correlation between UGT1A1 gene polymorphisms and severe delayed diarrhea or neutropenia and effect on response rate and progression-free survival were analyzed.

RESULTS

A total of 106 patients receiving irinotecan-based regimens and with detected UGT1A1 gene polymorphisms were enrolled in this research. According to our results, no significant differences of severe diarrhea were found in patients with UGT1A1*6 genotypes (p = 0.608). However, the incidence of severe diarrhea in patients with TA7/7 genotype (66.7%, 4/6) was significantly higher than that in patients with TA6/7 (31.5%, 6/19) or TA6/6 (1.28%, 1/78) genotypes (p < 0.001). The incidence of severe hematologic toxicity in patients with AA (100%, 2/2) was significantly higher than that in patients with GA (33.3%, 7/21) or GG genotype (7.23%, 6/83) (p = 0.011).

CONCLUSIONS

In terms of irinotecan-based regimens in cancers, UGT1A1*6 plays a more vital role in hematologic toxicity (p = 0.011) whereas UGT1A1*28 get more involved in diarrhea (p < 0.001).