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- W2022709664 abstract "Background: Aberrant Wnt pathway activation is a vital carcinogenic event in colorectal cancer (CRC). DKK1 and SFRP1 encode extracellular inhibitors of canonical and canonical/non-canonical Wnt signaling, respectively, that are frequently silenced by promoter hypermethylation in CRC. Despite their known tumor-suppressive roles, few studies have systematically examined the prognostic/predictive significance of methylation in these genes in tumor development. Using a population-based genetic epidemiological approach, we investigated the methylation status of DKK1 and SFRP1 in a large cohort of primary CRCs and correlations to patient clinicopathological data. Methods: As part of a Canadian interdisciplinary initiative to study the genetic and environmental determinants of CRC, we accrued a large number of primary colorectal carcinoma cases diagnosed in the province of Ontario, representative of a heterogeneous population (n = 558), and in the province of Newfoundland, representative of a founder population (n = 650). We examined the methylation status of DKK1 and SFRP1 gene promoters in colorectal tumors and matched normal colon tissues using MethyLight assay, a semi-quantitative methylation detection technique. We examined correlations between methylation levels and frequency, and a comprehensive array of patient clinicopathological features such as: age, sex, tumor stage, grade, tumor MSI subtype, and clinical outcome. Statistical analysis was performed using 2-tailed Fisher9s exact test, SPSS v16. Results: Respective DKK1 and SFRP1 methylation frequencies were similar in Ontario (13%, 95%) and Newfoundland (14%, 94%). Methylation was highly tumor specific. DKK1 methylation was a strong predictor of the microsatellite instability (MSI) tumor subtype in Ontario (OR=13.7 [7.8, 24.2], p Conclusion: Our study highlights the prognostic role of DKK1 and SFRP1 methylation related to CRC tumor subtype and suggests a novel distinction between the relative involvements of different Wnt pathways in microsatellite stable vs. unstable CRC. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B28" @default.
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- W2022709664 date "2010-04-01" @default.
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- W2022709664 title "Abstract B28: Epigenetic contribution of Wnt antagonists SFRP1 and DKK1 as prognostic markers in colorectal cancer" @default.
- W2022709664 doi "https://doi.org/10.1158/1078-0432.tcme10-b28" @default.
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