Genetic Variants in the IABCB1/I and IABCG2/I Gene Drug Transporters Involved in Gefitinib-Associated Adverse Reaction: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis aimed to verify the association between the genetic variants of adenosine triphosphate (ATP)-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) genes and the presence and severity of gefitinib-associated advers...

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Bibliographic Details
Published in:Genes 2024-05, Vol.15 (5)
Main Authors: Morau, Mariana Vieira, Seguin, Cecília Souto, Visacri, Marília Berlofa, Pincinato, Eder de Carvalho, Moriel, Patricia
Format: Article
Language:English
Subjects:
Adenosine triphosphate
Analysis
Antimitotic agents
Antineoplastic agents
Epidermal growth factor
Genes
Health aspects
Lung cancer, Non-small cell
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Summary:This systematic review and meta-analysis aimed to verify the association between the genetic variants of adenosine triphosphate (ATP)-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) genes and the presence and severity of gefitinib-associated adverse reactions. We systematically searched PubMed, Virtual Health Library/Bireme, Scopus, Embase, and Web of Science databases for relevant studies published up to February 2024. In total, five studies were included in the review. Additionally, eight genetic variants related to ABCB1 (rs1045642, rs1128503, rs2032582, and rs1025836) and ABCG2 (rs2231142, rs2231137, rs2622604, and 15622C>T) genes were analyzed. Meta-analysis showed a significant association between the ABCB1 gene rs1045642 TT genotype and presence of diarrhea (OR = 5.41, 95% CI: 1.38–21.14, I[sup.2] = 0%), the ABCB1 gene rs1128503 TT genotype and CT + TT group and the presence of skin rash (OR = 4.37, 95% CI: 1.51–12.61, I[sup.2] = 0% and OR = 6.99, 95%CI: 1.61–30.30, I[sup.2]= 0%, respectively), and the ABCG2 gene rs2231142 CC genotype and presence of diarrhea (OR = 3.87, 95% CI: 1.53–9.84, I[sup.2] = 39%). No ABCB1 or ABCG2 genes were positively associated with the severity of adverse reactions associated with gefitinib. In conclusion, this study showed that ABCB1 and ABCG2 variants are likely to exhibit clinical implications in predicting the presence of adverse reactions to gefitinib.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes15050591