Genetic Variants in the ABCB1 and ABCG2 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 ( ) and ATP-binding cassette subfamily G member 2 ( ) genes and the presence and severity of gefitinib-associated adverse reacti...

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Bibliographic Details
Published in:Genes 2024-05, Vol.15 (5), p.591
Main Authors: Morau, Mariana Vieira, Seguin, Cecília Souto, Visacri, Marília Berlofa, Pincinato, Eder de Carvalho, Moriel, Patricia
Format: Article
Language:English
Subjects:
ABC transporters
ABCG2 gene
Adenosine triphosphate
Antineoplastic Agents - adverse effects
ATP
ATP Binding Cassette Transporter, Subfamily B - genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics
Diarrhea
Drug dosages
Drug-Related Side Effects and Adverse Reactions - genetics
Gefitinib
Gefitinib - adverse effects
Genes
Genetic diversity
Genotype
Genotypes
Humans
Kinases
Lung diseases
Meta-analysis
Neoplasm Proteins - genetics
Patients
Polymorphism, Single Nucleotide
Quality of life
Reviews
Side effects
Toxicity
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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 ( ) and ATP-binding cassette subfamily G member 2 ( ) 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 (rs1045642, rs1128503, rs2032582, and rs1025836) and (rs2231142, rs2231137, rs2622604, and 15622C>T) genes were analyzed. Meta-analysis showed a significant association between the gene rs1045642 TT genotype and presence of diarrhea (OR = 5.41, 95% CI: 1.38-21.14, I = 0%), the gene rs1128503 TT genotype and CT + TT group and the presence of skin rash (OR = 4.37, 95% CI: 1.51-12.61, I = 0% and OR = 6.99, 95%CI: 1.61-30.30, I = 0%, respectively), and the gene rs2231142 CC genotype and presence of diarrhea (OR = 3.87, 95% CI: 1.53-9.84, I = 39%). No or genes were positively associated with the severity of adverse reactions associated with gefitinib. In conclusion, this study showed that and 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