AIM: To determine the methylation status and aberrant expression of some secreted frizzled-related protein (SFRP) genes in pancreatic cancer and explore their role in pancreatic carcinogenesis. METHODS: Methylation status and expression of SFRP genes were detected by methylation-specific PCR (MSPCR) and reverse-transcription PCR (RT-PCR) respectively. RESULTS: The frequencies of methylation for SFRP genes 1, 2, 4, 5 were 70%, 48.3%, 60% and 76.7% in pancreatic cancer samples, and 21.7%, 20%, 10% and 36.7% in matched cancer adjacent normal tissue samples, respectively (chi(2) = 28.23, P < 0.0001 for SFRP gene 1; chi(2) = 10.71, P = 0.001 for SFRP gene 2; chi(2) = 32.97, P < 0.0001 for SFRP gene 4; chi(2) 19.55, P < 0.0001 for SFRP gene 5). Expression loss of SFRP genes 1, 2, 4 and 5 was found in 65%, 40%, 55% and 71.7% of 60 pancreatic cancer samples, and 25%, 15%, 18.3% and 31.7% of matched cancer adjacent normal tissue samples, respectively (chi(2) = 19.39, P < 0.0001 for SFRP gene 1; chi(2) = 9.40, P = 0.002 for SFRP gene 2; chi(2) = 17.37, P < 0.0001 for SFRP gene 4; chi(2) = 19.22, P < 0.0001 for SFRP gene 5). SFRP gene 1 was methylated but not expressed in PC-3 and PANC-1, SFRP gene 2 was methylated but not expressed in PANC-1 and CFPAC-1, SFRP gene 4 was methylated but not expressed in PC-3, and SFRP gene 5 was methylated but not expressed in CFPAC-1. CONCLUSION: Hypermethylation and aberrant expression of SFRP genes are common in pancreatic cancer, which may be involved in pancreatic carcinogenesis. (c) 2008 The WJG Press. All rights reserved.