Preclinical studies have highlighted the importance of TS, the cellular target of 5-FU–folinic acid mechanism of action . Low TS was reported as a predictor of high response and long survival for AGC patients with high-dose 5-FU/LV . In colorectal cancer, both intratumoral TS and DPD gene expressions had been reported to be predictive for the effectiveness of 5-FU/LV or UFT/LV [11, 12]. However, there was no research on the prediction of OPRT, TS, TP, or DPD for efficacy or toxicity of S-1/LV or UFT/LV in gastric cancer. What is more, no available evidence existed on the predictive potential of CYP2A6 polymorphism for 5-FU/LV, UFT/LV, or S-1/LV treatment in gastric cancer. Interestingly, the use of more than single gene expression, such as the combination of low TS with high OPRT, or high OPRT/TS had been reported to be even more predictive of responders to S-1 or S-1 plus cisplatin in gastric cancer patients [13–15].