title: Biomarkers measured in buccal and blood leukocyte DNA as proxies for colon tissue global methylation.
abstract: There is increasing interest in clarifying the role of global DNA methylation levels in colorectal cancer (CRC) etiology. Most commonly, in epidemiologic studies, methylation is measured in DNA derived from blood leukocytes as a proxy measure of methylation changes in colon tissue. However, little is known about the correlations between global methylation levels in DNA derived from colon tissue and more accessible tissues such as blood or buccal cells. This cross-sectional study utilized DNA samples from a screening colonoscopy population to determine to what extent LINE-1 methylation levels (as a proxy for genome-wide methylation) in non-target tissue (e.g., blood, buccal cells) reflected methylation patterns of colon mucosal tissue directly at risk of developing CRC. The strongest Pearson correlation was observed between LINE-1 methylation levels in buccal and blood leukocyte DNA (r = 0.50; N = 67), with weaker correlations for comparisons between blood and colon tissue (r = 0.36; N = 280), and buccal and colon tissue (r = 0.27; N = 72). These findings of weak/moderate correlations have important implications for interpreting and planning future investigations of epigenetic markers and CRC risk.
authors: Department of Public Health Sciences, Queen's University Kingston, ON, Canada.
authors: Janet E
authors: JE
authors: Ashbury
authors: Department of Medical Genetics, University of Alberta Edmonton AB, Canada ; Molecular Diagnostics, Genetic Laboratory Services, Alberta Health Services Edmonton, AB, Canada.
authors: Sherryl A
authors: SA
authors: Taylor
authors: Department of Biomedical and Molecular Sciences, Queen's University Kingston, ON, Canada.
authors: M Yat
authors: MY
authors: Tse
authors: Department of Biomedical and Molecular Sciences, Queen's University Kingston, ON, Canada.
authors: Stephen C
authors: SC
authors: Pang
authors: Department of Medicine, Division of Gastroenterology, Hotel Dieu Hospital/Queen's University Kingston, ON, Canada.
authors: Jacob A
authors: JA
authors: Louw
authors: Department of Medicine, Division of Gastroenterology, Hotel Dieu Hospital/Queen's University Kingston, ON, Canada ; Gastrointestinal Diseases Research Unit (GIDRU), Queen's University Kingston, ON, Canada.
authors: Stephen J
authors: SJ
authors: Vanner
authors: Department of Public Health Sciences, Queen's University Kingston, ON, Canada.
authors: Will D
authors: WD
authors: King
keywords: LINE-1 DNA methylation; colorectal adenoma; colorectal cancer; correlation; global DNA methylation