Association between hypermethylation of DNA repetitive elements in white blood cell DNA and early-onset colorectal cancer

Walters, Rhiannon J., Williamson, Elizabeth J., English, Dallas R., Young, Joanne P., Rosty, Christophe, Clendenning, Mark, Walsh, Michael D., Parry, Susan, Ahnen, Dennis J., Baron, John A., Win, Aung Ko, Giles, Graham G., Hopper, John L., Jenkins, Mark A. and Buchanan, Daniel D. (2013) Association between hypermethylation of DNA repetitive elements in white blood cell DNA and early-onset colorectal cancer. Epigenetics, 8 7: 748-755. doi:10.4161/epi.25178

Author Walters, Rhiannon J.
Williamson, Elizabeth J.
English, Dallas R.
Young, Joanne P.
Rosty, Christophe
Clendenning, Mark
Walsh, Michael D.
Parry, Susan
Ahnen, Dennis J.
Baron, John A.
Win, Aung Ko
Giles, Graham G.
Hopper, John L.
Jenkins, Mark A.
Buchanan, Daniel D.
Title Association between hypermethylation of DNA repetitive elements in white blood cell DNA and early-onset colorectal cancer
Journal name Epigenetics   Check publisher's open access policy
ISSN 1559-2294
Publication date 2013-07-01
Year available 2013
Sub-type Article (original research)
DOI 10.4161/epi.25178
Open Access Status Not yet assessed
Volume 8
Issue 7
Start page 748
End page 755
Total pages 8
Place of publication Austin, United States
Publisher Landes Bioscience
Language eng
Subject 1312 Molecular Biology
1306 Cancer Research
Abstract Changes in the methylation levels of DNA from white blood cells (WBCs) are putatively associated with an elevated risk for several cancers. The aim of this study was to investigate the association between colorectal cancer (CRC) and the methylation status of three DNA repetitive elements in DNA from peripheral blood. WBC DNA from 539 CRC cases diagnosed before 60 years of age and 242 sex and age frequency-matched healthy controls from the Australasian Colorectal Cancer Family Registry were assessed for methylation across DNA repetitive elements Alu, LINE-1 and Sat2 using MethyLight. The percentage of methylated reference (PMR) of cases and controls was calculated for each marker. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression adjusted for potential confounders. CRC cases demonstrated a significantly higher median PMR for LINE-1 (p < 0.001), Sat2 (p < 0.001) and Alu repeats (p = 0.02) when compared with controls. For each of the DNA repetitive elements, individuals with PMR values in the highest quartile were significantly more likely to have CRC compared with those in the lowest quartile (LINE-1 OR = 2.34, 95%CI = 1.48–3.70; p < 0.001, Alu OR = 1.83, 95%CI = 1.17–2.86; p = 0.01, Sat2 OR = 1.72, 95%CI = 1.10–2.71; p = 0.02). When comparing the OR for the PMR of each marker across subgroups of CRC, only the Alu marker showed a significant difference in the 5-fluoruracil treated and nodal involvement subgroups (both p = 0.002). This association between increasing methylation levels of three DNA repetitive elements in WBC DNA and early-onset CRC is novel and may represent a potential epigenetic biomarker for early CRC detection.
Keyword Colorectal cancer
DNA methylation
Repetitive sequence
Peripheral blood
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 1025799
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 20 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 23 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 27 Oct 2013, 10:11:26 EST by System User on behalf of Molecular and Cellular Pathology - Sch Med South