Influence of drug transporters polymorphisms on severe adverse reaction caused by irinotecan in colorectal cancer patients

Abstract

Objective To investigate the influence of drug transporters (ABCB1-3435C>T and ABCC2-24C>T) polymorphisms on severe adverse reaction (mainly refers to grade 3~4 delayed diarrhea and neutropenia) caused by irinotecan in colorectal cancer patients. Methods A total of 91 colorectal cancer patients from Zhengzhou Central Hospital Affiliated to Zhengzhou University were enrolled in this study. Peripheral venous blood were collected. The genetic polymorphisms of ABCB1-3435C>T and ABCC2-24C>T were analyzed by PCR-Sanger sequence. The adverse reaction during chemotherapy were observed and recorded. The differences of the incidence of grade 3~4 adverse reaction were compared in patients with different genotypes. Results There is effect of ABCC2-24C>T polymorphisms on severe delayed diarrhea (χ2=5.067, P=0.024) but not neutropenia (χ2=3.107, P=0.078) in colorectal cancer patients. However, ABCB1-3435C>T polymorphisms don′t affect the severe adverse reaction caused by irinotecan (χ2=0.237, χ2=2.139, all P>0.05). Conclusion ABCC2-24C>T but not ABCB1-3435C>T mutation is related to severe toxicity caused by irinotecan in colorectal cancer patients. It can reduce severe adverse reaction that detecting ABCC2-24C>T mutation before using irinotecan. Key words: Colorectal neoplasms; Drug transporters; Genetic polymorphisms; Irinotecan; Adverse reaction