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Association of single-nucleotide polymorphisms in UGT1, NR1I2, ABCC2, ABCC5 and ABCG1 with irinotecan-induced toxicity in colorectal cancer BACKGROUND Irinotecan is used in the palliative treatment of metastatic colorectal cancer. Its metabolism is complex with many different transporters and enzymes involved. For UGT1A1*28 (rs8175347), an association with irinotecan-induced toxicity has been established. Recent studies suggested that other single-nucleotide polymorphisms (SNPs) within genes encoding irinotecan-related enzymes and transporters can lead to reduced or increased irinotecan-induced toxicity, mainly diarrhoea and neutropenia. OBJECTIVE In this study we aim to replicate associations between SNPs related to UGT1 rs11563250; NR1I2 rs10934498, rs2472677, rs3814055 and rs1523127; ABCC5 rs10937158, rs3749438, rs562 and rs2292997; ABCG1 rs225440 and ABCC2 rs717620 and grade 3 to 4 diarrhoea and febrile neutropenia in a population of 221 mCRC patients treated with irinotecan. The well-known UGT1A1*28 variant is also evaluated. DESIGN Retrospective clinical association study. METHODS DNA samples used for this study were obtained from patients participating in the CAIRO study (NCT00312000). The DNA samples were genotyped for twelve SNPs, selected on the basis of the results of previously published studies. For the main analysis, associations between SNPs and toxicity data were tested with logistic regression. RESULTS ABCC2 rs717620T is significantly associated with grade > 3 febrile neutropenia (OR = 2.72; P = 0.025). UGT1A1*28 shows significant associations with an increased risk on grade 3 to 4 diarrhoea (OR = 1.76, P = 0.035) and grade 3 to 4 febrile neutropenia (OR = 3; P = 0.01). CONCLUSION The outcomes of previous studies could not be replicated, except for UGT1A1*28. Moreover, we found an association with the opposite direction of effect between ABCC2 rs717620T and severe neutropenia. Based on the outcomes of this study genotyping for the tested variants - with exception of UGT1A1*28 - cannot be recommended. [ABSTRACT FROM AUTHOR]