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Genome-wide hypomethylation of LINE-1 and Alu retroelements in cell-free DNA of blood is an epigenetic biomarker of human aging.

ABSTRACT: Aging associated DNA hypomethylation of LINE-1 and Alu retroelements may be a crucial determinant of loss of genomic integrity, deterioration and cancer. In peripheral blood LINE-1 hypomethylation has been reported to increase during aging, but other studies did not observe significant changes. We hypothesized that these apparently inconsistent reports might relate to differences between cellular and cell-free DNA. Using the technique of idiolocal normalization of real-time methylation-specific PCR (IDLN-MSP) for genetic imbalanced DNA specimens we obtained evidence that LINE-1 hypomethylation in cell-free DNA, but not cellular DNA from peripheral blood is an epigenetic biomarker for human aging. Furthermore, hypomethylation of cell-free DNA is more extensive in smokers, suggesting that it might be used as a surrogate marker for monitoring the improvement of smoking-induced adverse effects after cancelling smoking.

SUBMITTER: Erichsen L

PROVIDER: S-EPMC6117241 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Genome-wide hypomethylation of LINE-1 and Alu retroelements in cell-free DNA of blood is an epigenetic biomarker of human aging.

Erichsen Lars L Beermann Agnes A Arauzo-Bravo Marcos J MJ Hassan Mohamed M Dkhil Mohamed A MA Al-Quraishy Saleh S Hafiz Taghreed A TA Fischer Johannes C JC Santourlidis Simeon S

Saudi journal of biological sciences 20180213 6

Aging associated DNA hypomethylation of LINE-1 and Alu retroelements may be a crucial determinant of loss of genomic integrity, deterioration and cancer. In peripheral blood LINE-1 hypomethylation has been reported to increase during aging, but other studies did not observe significant changes. We hypothesized that these apparently inconsistent reports might relate to differences between cellular and cell-free DNA. Using the technique of idiolocal normalization of real-time methylation-specific ...[more]

PMID: 30174526

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Project description:ObjectiveA systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other tissues as an epigenetic marker for cancer risk.MethodsA systematic literature search in the Medline database, using PubMed, was conducted for epidemiological studies, published before March 2014. The random-effects model was used to estimate weighted mean differences (MDs) with 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by sample type (tissue or blood samples), cancer types, and by assays used to measure global DNA methylation levels. The Cochrane software package Review Manager 5.2 was used.ResultsA total of 19 unique articles on 6107 samples (2554 from cancer patients and 3553 control samples) were included in the meta-analysis. LINE-1 methylation levels were significantly lower in cancer patients than in controls (MD: -6.40, 95% CI: -7.71, -5.09; p<0.001). The significant difference in methylation levels was confirmed in tissue samples (MD -7.55; 95% CI: -9.14, -65.95; p<0.001), but not in blood samples (MD: -0.26, 95% CI: -0.69, 0.17; p?=?0.23). LINE-1 methylation levels were significantly lower in colorectal and gastric cancer patients than in controls (MD: -8.33; 95% CI: -10.56, -6.10; p<0.001 and MD: -5.75; 95% CI: -7.75, -3.74; p<0.001) whereas, no significant difference was observed for hepatocellular cancer.ConclusionsThe present meta-analysis adds new evidence to the growing literature on the role of LINE-1 hypomethylation in human cancer and demonstrates that LINE-1 methylation levels were significantly lower in cancer patients than in control samples, especially in certain cancer types. This result was confirmed in tissue samples, both fresh/frozen or FFPE specimens, but not in blood. Further studies are needed to better clarify the role of LINE-1 methylation in specific subgroups, considering both cancer and sample type, and the methods of measurement.

Dataset Information

Genome-wide hypomethylation of LINE-1 and Alu retroelements in cell-free DNA of blood is an epigenetic biomarker of human aging.

Publications

Genome-wide hypomethylation of LINE-1 and Alu retroelements in cell-free DNA of blood is an epigenetic biomarker of human aging.

Similar Datasets

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