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Meta-Analysis
. 2020 Oct 30;40(10):BSR20200576.
doi: 10.1042/BSR20200576.

Association of UGT1A1*6 polymorphism with irinotecan-based chemotherapy reaction in colorectal cancer patients: a systematic review and a meta-analysis

Xiaoyun Zhu #  1 , Ruchao Ma #  2 , Xin Ma  1 , Gang Yang  1
Affiliations
Meta-Analysis

Association of UGT1A1*6 polymorphism with irinotecan-based chemotherapy reaction in colorectal cancer patients: a systematic review and a meta-analysis

Xiaoyun Zhu et al. Biosci Rep. .

Abstract

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 CRC. Nine articles comprising 1652 patients were included in the final combination. Meta-analysis showed G allele or GG had a lower risk of severe late-onset diarrhea compared with A/AA in allele model and homozygote model (G vs. A: OR = 0.53, 95% CI: 0.28-0.99, P=0.05; GG vs. AA: OR = 0.48, 95% CI: 0.23-0.99, 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: 0.46-0.71, P=0.00; GG vs. AA: OR = 0.28, 95% CI: 0.17-0.45, P=0.01; GA vs. AA: OR = 0.42, 95% CI: 0.26-0.70, P=0.00; GG+GA vs. AA: OR = 0.32, 95% CI: 0.20-0.52, P=0.00; GG vs. AA+GA: OR = 0.40, 95% CI: 0.22-0.71, 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 IRI-based chemotherapy in CRC.

Keywords: UGT1A1; colorectal cancer; irinotecan; meta-analysis; response; rs4148323.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Flow diagram of the study selection process
Figure 2
Figure 2. Forests for UGT1A1*6 polymorphism and IRI-based chemotherapy RR
(A) Represents allele model (G vs. A); (B) represents homozygote model (GG vs. AA); (C) represents heterozygote model (GA vs. AA); (D) represents dominant model (GG+GA vs. AA); (E) represents recessive model (GG vs. GA+AA).
Figure 3
Figure 3. Forests for UGT1A1*6 polymorphism and IRI-based chemotherapy DCR
(A) Represents allele model (G vs. A); (B) represents homozygote model (GG vs. AA); (C) represents heterozygote model (GA vs. AA); (D) represents dominant model (GG+GA vs. AA); (E) represents recessive model (GG vs. GA+AA).
Figure 4.1
Figure 4.1. Forests for UGT1A1*6 polymorphism and IRI-induced severe late-onset diarrhea
(A) Represents allele model (G vs. A); (B) represents homozygote model (GG vs. AA); (C) represents heterozygote model (GA vs. AA); (D) represents dominant model (GG+GA vs. AA); (E) represents recessive model (GG vs. GA+AA).
Figure 4.2
Figure 4.2. Forests for UGT1A1*6 polymorphism and IRI-induced severe late-onset diarrhea
(A) Represents sensitive analysis in allele model; (B) represents the results of removing heterogeneity in allele model; (C) represents sensitive analysis in recessive model; (D) represents the results of removing heterogeneity in recessive model.
Figure 5.1
Figure 5.1. Forests for UGT1A1*6 polymorphism and IRI-induced severe neutropenia
(A) Represents allele model (G vs. A); (B) represents homozygote model (GG vs. AA); (C) represents heterozygote model (GA vs. AA); (D) represents dominant model (GG+GA vs. AA); (E) represents recessive model (GG vs. GA+AA).
Figure 5.2
Figure 5.2. Forests for UGT1A1*6 polymorphism and IRI-induced severe neutropenia
(A) Represents sensitive analysis in recessive model; (B) represents the results of removing heterogeneity in recessive model.
Figure 6
Figure 6. Forests for Begg’s test for RR
(A) Represents allele model (G vs. A); (B) represents homozygote model (GG vs. AA); (C) represents heterozygote model (GA vs. AA); (D) represents dominant model (GG+GA vs. AA); (E) represents recessive model (GG vs. GA+AA).
Figure 7
Figure 7. Forests for Begg’s test for DCR
(A) Represents allele model (G vs. A); (B) represents homozygote model (GG vs. AA); (C) represents heterozygote model (GA vs. AA); (D) represents dominant model (GG+GA vs. AA); (E) represents recessive model (GG vs. GA+AA).
Figure 8
Figure 8. Forests for Begg’s test for IRI-induced severe late-onset diarrhea
(A) Represents allele model (G vs. A); (B) represents homozygote model (GG vs. AA); (C) represents heterozygote model (GA vs. AA); (D) represents dominant model (GG+GA vs. AA); (E) represents recessive model (GG vs. GA+AA).
Figure 9
Figure 9. Forests for Begg’s test for IRI-induced severe neutropenia
(A) Represents allele model (G vs. A); (B) represents homozygote model (GG vs. AA); (C) represents heterozygote model (GA vs. AA); (D) represents dominant model (GG+GA vs. AA); (E) represents recessive model (GG vs. GA+AA).
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