We tested the hypothesis that the clinical outcomes of chemotherapy (response rate, time to progression, and overall survival) in patients with advanced GC are related to the pretreatment intratumour mRNA levels of enzymes participating in critical pathways of drug resistance, such as 5-FU and folate metabolism (TS, DPD, TP, OPRT, DHFR, MTHFR), DNA repair (ERCC1), the EGFR signalling pathway (EGFR), and tumour-related angiogenesis (VEGF-A). This evidence concerns the gene MTHFR and gastric cancer.