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

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.