Variation risks of SFRP2 hypermethylation between precancerous disease and colorectal cancer.

DNA hypermethylation of secreted frizzled-related protein 2 (SFRP2) gene associated with the Wnt signaling pathway has been studied previously. However, the risk size and changing rules between colorectal cancer (CRC) and SFRP2 hypermethylation from precancerous disease to CRC remain unclear. The aim of work was therefore to investigate the risk size and changing rule based on detections on large numbers of tissue and feces samples. Association study and meta-analysis were performed to analyze the risk size of SFRP2 hypermethylation in tissue and fecal detections from 2,912 samples, including 1,436 patients with CRC, 866 patients with colon adenomas or polyps, and 610 samples with both normal controls. Based on normal controls as standard reference, the analysis showed that SFRP2 hypermethylation in CRC and adenoma tissues had a significantly higher risk with 92.81 (28.76-299.45) and 22.46 (4.13-122.04) odds ratio (OR) (95 % confidence interval (CI)) respectively, and that the risk sizes of SFRP2 hypermethylation in CRC and adenoma patients were 41.86 (18.91-92.67) and 11.76 (6.98-19.84) of OR (95 % CI) in fecal samples, and that the OR risk in both tissue and fecal samples increased significantly to 70.35 and 30.10 from precancerous disease (adenoma or polyp) to CRC. There were significant differences between tissue and fecal hypermethylation frequency. On the basis of the hypermethylation frequency of colorectal tissue, the coincidence rates of fecal hypermethylation in CRC and colorectal adenoma were 0.89 and 0.9, respectively. The risk size of SFRP2 hypermethylation from normal control to adenoma or polyp as well as from adenoma or polyp to CRC increased gradually in both tissue and feces. Therefore, SFRP2 hypermethylation is an important biomarker both in noninvasive diagnosis in feces detection and in colon tissue.