Impact of ABCG2 rs2231142(421C>A) Variant on the Clinical Outcomes of Patients With EGFR-mutated Non-small Cell Lung Cancer Treated With Gefitinib: A Comprehensive Meta-analysis

Anticancer Res. 2024 Dec;44(12):5361-5370. doi: 10.21873/anticanres.17363.

Abstract

Background/aim: Lung cancer accounts for the largest percentage of cancer deaths worldwide, with non-small cell lung cancer (NSCLC) being the predominant type. Gefitinib, an EGFR tyrosine kinase inhibitor (EGFR-TKI), has shown marked efficacy in NSCLC patients with an EGFR mutation. However, gefitinib resistance because of ABCG2 polymorphisms such as rs2231142(421C > A) might limit its clinical use.

Patients and methods: This meta-analysis followed the PRISMA guidelines and investigated the impact of the ABCG2 rs2231142 variant on gefitinib treatment outcomes in patients with NSCLC, using the PECOS model for study selection.

Results: A total of 585 NSCLC patients treated with gefitinib were assessed for the association between genetic variants of the ABC transporter genes, specifically the ABCG2 C421A polymorphism, and clinical outcomes. No association was found between the ABCG2 C421A polymorphism and response to gefitinib chemotherapy (p=0.653; I2=0%). Similarly, no correlation was observed with gefitinib-induced skin rash (p=0.161177; I2=0%), diarrhea (p=0.064441), hepatotoxicity (p=0.210916; I2=0%), or interstitial pneumonia (p=0.138937).

Conclusion: The ABCG2 rs2231142 polymorphism plays a significant role in the clinical outcomes of patients with EGFR-mutated NSCLC treated with gefitinib, warranting further investigation to clarify its impact on treatment efficacy and patient safety.

Keywords: ABCG2 polymorphism; EGFR; Non-small cell lung cancer; gefitinib; meta-analysis; rs2231142; treatment outcomes.

Publication types

  • Meta-Analysis

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2* / genetics
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • ErbB Receptors* / genetics
  • Gefitinib* / therapeutic use
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mutation*
  • Neoplasm Proteins* / genetics
  • Polymorphism, Single Nucleotide
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Treatment Outcome

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Gefitinib
  • ABCG2 protein, human
  • ErbB Receptors
  • Neoplasm Proteins
  • EGFR protein, human
  • Antineoplastic Agents
  • Protein Kinase Inhibitors