Correlation between MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC: A meta-analysis

• Published in: Pteridines Vol. 32; no. 1; pp. 23 - 32
• Main Authors: Han, Feng, Xu, Wengui
• Format: Journal Article
• Language: English
• Published: Innsbruck De Gruyter 14.05.2021; Walter de Gruyter GmbH
• Subjects: Chemotherapy; chemotherapy response; Confidence intervals; Disease control; Genotype & phenotype; Meta-analysis; mthfr; NSCLC; pemetrexed; Polymorphism; Statistical analysis
• ISSN: 2195-4720; 0933-4807; 2195-4720
• DOI: 10.1515/pteridines-2020-0026

Abstract Objective The aim of this study was to investigate the correlation between MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in advanced non-small-cell lung cancer (NSCLC) by pooling the open published relevant studies. Methods Clinical studies associated with MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC were systematically searched in databases of Pubmed, Embase, Cochrance Library, China national knowledge infrastructure (CNKI) and Wanfang. The correlation was expressed by odds ratio (OR) and corresponding 95% confidence interval (95% CI). The publication bias of the included studies was evaluated through Begg’s funnel plot and Egger’s line regression test. Results Ten prospective clinical studies relevant to MTHFR 677C > T polymorphism and response of pemetrexed-based chemotherapy in NSCLC were included in the present meta-analysis. The pooled results indicated that the partial response in NSCLC patients with TT or CT genotype was inferior to CC genotype in a dominant gene model (TT + CT vs CC) (OR = 0.16, 95% CI: 0.06–0.41, P = 0.001). NSCLC cases with T genotype were inferior to C genotype in the objective response rate treated with pemetrexed-based chemotherapy for dominant (OR = 0.28, 95% CI: 0.18–0.45, P = 0.001), recessive (OR = 0.43, 95% CI: 0.19–0.94, P = 0.03) and homozygous models (OR = 0.30, 95% CI: 0.13–0.67, P = 0.003). However, there was no statistical difference in disease control rate, progressive disease between different genotypes of different gene models ( P all > 0.05). Conclusion The pemetrexed-based chemotherapy response was decreased in NSCLC cases with T genotype, which can be applied as a potential pemetrexed-based chemotherapy response marker.