Colorectal cancer (CRC) is a leading cause of cancer-related deaths across the world. Irinotecan (IRI) is commonly used to treat CRC, and IRI-based chemotherapy is linked with adverse reaction and the efficacy of the treatment regimen. The gene UGT1A1 plays a central role in the IRI metabolic pathway. A polymorphism UGT1A1*6 has been widely researched which may be related to response of IRI-based chemotherapy in CRC. All relevant studies were strictly searched from PubMed, Embase, Cochrane Library and Web of science databases to explore the associations between UGT1A1*6 and response of IRI-based chemotherapy with colorectal cancer. Nine articles comprising 1652 patients were included in the final combination. Meta-analysis showed G allele or GG had a lower risk of server late-onset diarrhea compared to A/AA in allele model and homozygote model (G vs. A: OR=0.53, 95% CI: 0.28 to 0.99, P=0.05; GG vs. AA: OR=0.48, 95% CI: 0.23 to 0.99, P=0.05), no significant association was observed in other models. In addition, a significant association between UGT1A1*6 and neutropenia was observed in all models (G vs. A: OR=0.57, 95% CI: 0.46 to 0.71, P=0.00; GG vs. AA: OR=0.28, 95% CI:0.17 to 0.45, P=0.01; GA vs. AA: OR=0.42, 95% CI: 0.26 to 0.70, P=0.00; GG+GA vs. AA: OR=0.32, 95% CI: 0.20 to 0.52, P=0.00; GG vs. AA+GA: OR=0.40, 95% CI: 0.23 to 0.71, P=0.00), whereas, no relationship was found between UGT1A1*6 and clinical response among the different genotypes. UGT1A1*6 may be considered as a biomarker for chemotherapy of IRI-based chemotherapy in colorectal cancer.

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