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

Xiaoyun Zhu,Gang Yang,Xin Ma,Ruchao Ma

doi:10.1042/bsr20200576

Xiaoyun Zhu, Gang Yang + Show 2 more

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https://doi.org/10.1042/bsr20200576

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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.

Highlights

Colorectal cancer (CRC) is the third most common cancer and the most common cause of deaths all over the world [1]
After different levels of screening based on titles, abstracts and full texts, 156 articles were reviews or meta-analysis, 10 studies were case reports, 129 articles seemed to be not related to this research, 67 studies that were not related to UGT1A1*6 and 15
Our results showed that UGT1A1*6 polymorphism was associated with IRI-induced severe neutropenia (Figure 5.1): (1) allele model: (G vs. A: odds ratio (OR) = 0.57, 95% confidence intervals (95% CIs): 0.46–0.71, P=0.00); (2) homozygote model: (GG vs. AA: OR = 0.28, 95% CI: 0.17–0.45, P=0.00); (3) heterozygote model: (GA vs. AA: OR = 0.42, 95% CI: 0.26–0.70, P=0.00); (4) dominant model: (GG+GA vs. AA: OR = 0.32, 95% CI: 0.20–0.52, P=0.00)

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer and the most common cause of deaths all over the world [1]. The colon-endoscopy is extensively used to screen the high-risk patients, and some new biomarkers are widely used, such as carcino-embryonic antigen (CEA) and carbohydrate antigen 199 (CA199) [2], the early diagnosis of CRC is difficult, and some patients reach a critical size to produce complications. Some new oncogenes were found which play a pivotal role, and many new gene-related biomarkers were widely researched [3,4]. Irinotecan (IRI) is a widely used chemotherapeutic drug in malignant cancer especially in CRC, which can prolong survival time and improve the prognosis in CRC patients [5]. The responses of the drug present obvious differences in different individuals [5,6], so a plenty of researches have attempted to explore the reasons. Genome-wide association studies have demonstrated that many coding or non-coding variants, especially low-frequency

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