Effects of ABCC2 and SLCO1B1 Polymorphisms on Treatment Responses in Thai Metastatic Colorectal Cancer Patients Treated with Irinotecan-Based Chemotherapy

Document Type: Research Articles

Authors

1 Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

2 Department of Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Abstract

Purpose: Irinotecan is an anticancer medicine which is used mostly in metastatic colorectal cancer (mCRC) treatment
as second or third line chemotherapy. Several factors affect its efficacy and toxicity, including pharmacogenomics.
This study aimed to investigate the impacts of ABCC2 and SLCO1B1 polymorphisms on treatment responses in
irinotecan-based chemotherapy in 49 Thai mCRC patients. Materials and Methods: Forty-nine participants with
mCRC enrolled in this study received irinotecan-based chemotherapy from January to June 2017. Genotypic analyses of
ABCC2 (C>T, rs717620) and SLCO1B1 (A>G, rs2306283) were performed. Treatment responses were evaluated after
at least three cycles of chemotherapy were given. Results: Allele frequencies of ABCC2 (C>T) and SLCO1B1 (A>G)
were found at 18.37% and 78.57%, respectively. Neither was associated with treatment responses. However, combined
genotypes of ABCC2 and SLCO1B1 tended to be associated with clinical benefits in terms of partial responses (PR) and
stable disease (SD). All patients (100%) with at least one variant allele of SLCO1B1 and ABCC2 were in a PR or SD
group, while patients with other genotypes had progressive disease (PD) at 45.5% to 70%, (p = 0.059). Conclusion:
The combined effect of ABCC2 and SLCO1B1 polymorphisms tended to be associated with treatment responses in
irinotecan-based treated mCRC patients. Therefore, such polymorphisms could be factors impacting inter-individual
variation of irinotecan efficacy in Thai mCRC patients.

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