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AIM: To identify the methylation of secreted frizzledrelated protein 1 (SFRP1) in gastric cancer and to investigate the aberrant expression of SFRP1 and its correlation with the clinical pathological features of patients.METHODS: We determined SFRP1 methylation and SFRP1 mRNA expression in 3 gastric cancer cell lines SGC-7901, BGC-823, HGC-27, from 52 primary gastric cancer specimens and matched tumor adjacent tissue specimens by methylation-specific (MSP) PCR and RTPCR respectively. Fisher's exact test was used to analyze the statistical association between clinical pathological data and aberrant expression of SFRP1.RESULTS: In 3 cancer cell lines, BGC-823 and HGC-27 had methylated SFRP1 and lost SFRP1 mRNA expression.After treatment of BGC-823 and HGC-27 with the demethylating agent, 5-aza-2'-deoxycytidine, SFRP1 was re-expressed. In 52 primary gastric cancer specimens and matched tumor adjacent tissue specimens,hypermethylation of SFRP1 was detected in 23 (44%)and 8 (15%) specimens respectively (x2= 10.34,P ＜ 0.01). Loss of SFRP1 expression was detected in 17(33%) and 6 (12%) specimens respectively (x2= 6.75,P ＜ 0.01). There was a significant correlation between SFRP1 hypermethylation and SFRP1 expression loss.SFRP1 expression was also correlated significantly with tumor stage and lymph node status, but not with patient sex, age and histological type.CONCLUSION: SFRP1 inactivation is a common and early event caused mainly by hypermethylation in gastric cancer. SFRP1 expression loss may be correlated with tumor metastasis in primary gastric cancer.