Title |
Epigenome-wide discovery and evaluation of leukocyte DNA methylation markers for the detection of colorectal cancer in a screening setting
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Published in |
Clinical Epigenetics, March 2017
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DOI | 10.1186/s13148-017-0322-x |
Pubmed ID | |
Authors |
Jonathan Alexander Heiss, Hermann Brenner |
Abstract |
Colorectal cancer (CRC) is the third most common cancer worldwide. If detected at an early stage, prognosis is good. Despite increasing evidence for the benefits of implemented screening programs, such as screening colonoscopy, compliance is rather low. Hence there is demand for non-invasive tests for the early detection of CRC with high acceptance in population-wide screening. The objective of this study was to identify and evaluate leukocyte DNA methylation patterns as a potential biomarker for early detection of CRC. Blood samples of patients scheduled for a screening colonoscopy were collected before the procedure. Additionally, blood samples from CRC cases recruited in a clinical setting were collected. DNA was extracted from leukocytes, and DNA methylation was measured with the Infinium 450K BeadChip. In total, 46 CRC cases and 140 controls from the screening setting and 93 CRC cases from the clinical setting were measured. An epigenome-wide discovery revealed two CpG sites in the promoter region of KIAA1549L that were significantly differentially methylated between cases and controls. A third marker in the body region of BCL2 was discovered in a candidate approach testing biomarkers reported in the literature. Logistic regression models built on these three markers yielded an optimism-corrected c-statistic of 0.69 in the screening setting and 0.73 in the clinical setting. Although diagnostic performance of the DNA methylation signature identified in this first epigenome-wide association study of leukocyte DNA methylation with CRC in a screening setting is not competitive with established screening tests, the identified markers may contribute to multimarker panels for early detection of CRC. |
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