Relevance of MTHFR polymorphisms with response to fluoropyrimidine-based chemotherapy in oesophagogastric cancer: A meta-analysis

Abstract

Objective To evaluate the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the response to fluoropyrimidine-based chemotherapy in oesophagogastric cancer. Design Meta-analysis. Methods We searched PubMed, Embase and Web of Science databases from inception up to October 2017 for relevant studies. The statistical analysis was performed using STATA V.12.0 software. The pooled ORs and 95% CIs were used to assess the strength of the association under the allele, dominant and recessive models. We also conducted subgroup analysis stratified by cancer type, ethnicity and study design. Additionally, the sensitivity analysis was performed by sequential omission of individual studies, and the publication bias was detected using both Begg's test and Egger's test. Results A total of 2020 patients from 12 studies were included in this meta-analysis. The results showed that there was no significant association between MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and the clinical response to fluoropyrimidine-based chemotherapy under all of the three genetic models (T vs C: OR 0.93, 95% CI 0.76 to 1.15; C vs A: OR 0.88, 95% CI 0.56 to 1.40. CT+TT vs CC: OR 0.94, 95% CI 0.72 to 1.23; AC+CC vs AA: OR 0.80, 95% CI 0.47 to 1.35. TT vs CC+CT: OR 1.02, 95% CI 0.74 to 1.39; CC vs AA+AC: OR 1.15, 95% CI 0.50 to 2.67). When stratified by cancer type, ethnicity or study design, the association was still not significant in all subgroups. Conclusions This meta-analysis suggested that MTHFR polymorphisms could not be considered as reliable factors for predicting the response to fluoropyrimidine-based chemotherapy in oesophagogastric cancer.