Background: CCL2/CCR2 chemokine axis controls the recruitment of leukocytes to tissues during inflammation and has a number of tumor-promoting activities including the polarization of tumor associated macrophages which play immunosuppressive roles. Overexpression of CCL2 was associated with a higher risk of gastric cancer. We hypothesized that single nucleotide polymorphisms (SNPs) in genes encoding for CCL2/CCR2 axis may be associated with clinical outcome in pts with localized AGC. Methods: This study included 160 Japanese pts for evaluation set and 104 U.S. pts for validation set, with localized AGC treated with surgery alone or plus adjuvant therapy (stage Ib-IV; AJCC-6^th). The median age were 68 (31-88) and 59 (26-85) years-old, median follow-up were 4 and 3.3 years, respectively. Genomic DNA was extracted from pts’ blood or tissues. Seven functional SNPs in genes encoding for CCL2/CCR2 axis, CCL2 (rs4586 and rs1024611) and CCR2 (rs743660, rs1799864, rs3138042, rs3918358, and rs3092964), were analyzed by PCR-based direct sequencing for association with disease-free survival (DFS) / time to recurrence (TTR) and overall survival (OS). Results: In the evaluation set, the univariate analysis showed pts with any T allele of CCL2 rs4586 had significantly longer DFS and OS compared to those with the C/C genotype (HR: 0.61; 95% CI: 0.39-0.96; P=0.03, HR: 0.58; 95% CI: 0.36-0.93; P=0.02, log-rank test, respectively) although median DFS and OS both had not been reached yet. This remained no significant upon multivariate analysis. In the validation set, pts with any T allele of CCL2 rs4586 had a trend toward shorter TTR (HR: 1.73; P=0.07) and significantly shorter OS compared to those with the C/C genotype (3.8 vs. 7.3 yrs; HR: 2.43; 95% CI: 1.14-5.18; P=0.01, log-rank test) in univariate analysis. Interestingly, the impact of the T allele on OS in the U.S. cohort was the opposite to that in the JPN cohort and reached statistical significance (P=0.001). Conclusions: Our results suggest that the CCL2 polymorphism, rs4586, may serve as a prognostic marker in pts with localized AGC and that there may be ethnic differences in immunoesurveillance impacting clinical outcome.