Effects of ABCC2 and SLCO1B1 polymorphisms on the treatment responses of irinotecan-based chemotherapy in Thai metastatic colorectal cancer patients

Abstract

Irinotecan, anticancer which is mostly used in metastatic colorectal cancer (mCRC) as a second or third line chemotherapy. Several factors affect its efficacy and toxicity, including pharmacogenomics. This study was aimed to investigate the impacts of ABCC2 and SLCO1B1 polymorphisms on treatment responses and severe toxicities of irinotecan-based chemotherapy in Thai mCRC patients. Fifty-six participants with mCRC received irinotecan-based chemotherapy were enrolled into this prospective cohort study. Analysis of ABCC2 (C>T, rs717620) and SLCO1B1 (A>G, rs2306283) genotypes were performed. Allele frequencies of ABCC2 (C>T) and SLCO1B1 (A>G) were found at 17.86% and 76.79%, respectively. Neither of them associated with treatment responses. However, patients with allele T of ABCC2 and allele A of SLCO1B1 were associated with higher rate of clinical benefit from chemotherapy than the other group (100 % vs. 51.1%, P = 0.031). For toxicities, it was found that the risk of severe anemia, severe neutropenia and severe diarrhea were observed higher in patient with homozygous wild type (AA) of SLCO1B1 than other genotypes. This study can be concluded that combined effect of ABCC2 and SLCO1B1 polymorphisms was associated with clinical benefit of irinotecan-based chemotherapy in Thai mCRC patients.