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Predictive Value of UGT1A1*28 Polymorphism In Irinotecan-based Chemotherapy
Xing-Han Liu1, Jun Lu2, Wei Duan3
1Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Journal of Cancer
|April 4, 2017
Summary
The UGT1A1*28 polymorphism is linked to increased irinotecan toxicity, specifically severe diarrhea and neutropenia. However, this genetic variant also correlates with a better chemotherapy response, suggesting its utility in monitoring cancer patients.
Area of Science:
- Pharmacogenomics
- Oncology
Background:
- The UGT1A1*28 polymorphism's association with irinotecan efficacy and toxicity is debated.
- Previous studies have yielded conflicting results regarding this genetic marker.
Purpose of the Study:
- To conduct a meta-analysis investigating the impact of the UGT1A1*28 polymorphism on severe diarrhea, neutropenia, and treatment response in patients undergoing irinotecan-based chemotherapy.
- To clarify the controversial findings from prior research.
Main Methods:
- A systematic literature search was performed across PubMed, Web of Science, Wanfang, and CNKI databases.
- Clinical trials examining the UGT1A1*28 polymorphism's link to irinotecan-induced severe diarrhea, neutropenia, and response were included.
- Combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models.
Main Results:
- The meta-analysis included 58 studies with 6087 cancer patients.
- Patients with TA6/7 and TA7/7 genotypes exhibited higher rates of diarrhea (OR=2.18) and neutropenia (OR=2.15) compared to TA6/6, especially those with metastatic colorectal cancer.
- Patients with TA6/7+TA7/7 genotypes showed an improved response to chemotherapy (OR=1.20), notably Caucasians and those with metastatic colorectal cancer.
Conclusions:
- The UGT1A1*28 polymorphism significantly influences both toxicity and response to irinotecan-based chemotherapy.
- This genetic polymorphism may serve as a valuable monitoring index for cancer patients receiving irinotecan therapy.