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

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.

LINE-1 in cancer: multifaceted functions and potential clinical implications

“…Compared with normal controls, L1 hypermethylation was observed in white blood cells of pancreatic, 49 epithelial ovarian, 50 and colorectal 51 cancer patients. As for melanoma 52 and HCC, 53 serum L1s were hypomethylated relative to normal controls.…”

The Association and Clinical Significance of CDKN2A Promoter Methylation in Head and Neck Squamous Cell Carcinoma: a Meta-Analysis

“…However, because of nonspecific symptoms in the early stage and lack of effective diagnostic biomarkers, a low early diagnostic rate brings challenges for effective treatment. Abnormal methylation biomarkers have proven to be useful in diagnosing numerous cancers [102,103]. In the current study, the results demonstrated that the combined sensitivity, specificity, and AUC values of CDKN2A methylation were 0.36, 0.96, and 0.77, respectively, indicating that detection of CDKN2A promoter methylation has a moderate diagnostic accuracy for HNSCC.…”

Different EPHX1 methylation levels in promoter area between carbamazepine-resistant epilepsy group and carbamazepine-sensitive epilepsy group in Chinese Population

“…In this study, we investigated EPHX1 methylation in the peripheral blood DNA and tested the association between CBZ-metabolites concentration. Methylation levels in peripheral blood DNA have been widely investigated in various diseases, including diabetes [23], obesity [24], major depression [25], and various cancers [26][27][28]. Here we provided its strong association with lower CBZ-metabolites concentration in CBZ-resistant group.…”