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United States Department of Agriculture

Agricultural Research Service

Research Project: ONE-CARBON NUTRIENTS IN THE PREVENTION OF CANCER

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk)

Author
item Friso, Simonetta
item Udali, Silvia
item Guarini, Patrizia
item Pellegrini, Camilla
item Pattini, Patrizia
item Moruzzi, Sara
item Girelli, Domenico
item Pizzolo, Francesca
item Martinelli, Nicola
item Corrocher, Roberto
item Olivieri, Oliviero
item Choi, Sang-woon

Submitted to: Cancer Epidemiology Biomarkers and Prevention
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/11/2012
Publication Date: 1/8/2013
Citation: Friso, S., Udali, S., Guarini, P., Pellegrini, C., Pattini, P., Moruzzi, S., Girelli, D., Pizzolo, F., Martinelli, N., Corrocher, R., Olivieri, O., Choi, S. 2013. Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk. Cancer Epidemiology Biomarkers and Prevention. 22(3):348-355.

Interpretive Summary: DNA methylation is a chemical modification of DNA, a nucleic acid that carries the genetic information in the cell. In the present study, we found that the level of DNA methylation in blood cells can be a biomarker to predict the presence or future occurrence of cancer. Interestingly, the levels of blood DNA methylation are highly correlated with blood folate concentrations, a water soluble B vitamin, and a gene associated with folate metabolism.

Technical Abstract: Global DNA hypomethylation is an early molecular event in carcinogenesis. Whether methylation measured in peripheral blood mononuclear cells (PBMCs) DNA is a clinically reliable biomarker for early detection or cancer risk assessment is to be established. From an original sample-set of 753 male and female adults (ages 64.8 +/- 7.3 years), PBMCs DNA methylation was measured in 68 subjects with history of cancer at time of enrollment and 62 who developed cancer during follow-up. Age- and sex-matched controls for prevalent and incident cancer cases (n = 68 and 58, respectively) were also selected. Global DNA methylation was assessed by liquid chromatography/mass spectrometry (LC/MS). Methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype and plasma folate concentrations were also determined for the known gene-nutrient interaction affecting DNA methylation. Cancer subjects had significantly lower PBMCs-DNA methylation than controls [4.39 (95% confidence intervals (CI), 4.25-4.53) vs. 5.13 (95% CI, 5.03-5.21) %mCyt/(mCyt+Cyt); P < 0.0001]. A DNA methylation threshold of 4.74% clearly categorized patients with cancer from controls so that those with DNA methylation less than 4.74% showed an increased prevalence of cancer than those with higher levels (91.5% vs. 19%; P < 0.001). Subjects with cancer at follow-up had, already at enrollment, reduced DNA methylation as compared with controls [4.34 (95% CI, 4.24-4.51) vs. 5.08 (95% CI, 5.05-5.22) %mCyt/(mCyt+Cyt); P < 0.0001]. Moreover, MTHFR677C>T genotype and folate interact for determining DNA methylation, so that MTHFR677TT carriers with low folate had the lowest DNA methylation and concordantly showed a higher prevalence of cancer history (OR, 7.04; 95% CI, 1.52-32.63; P = 0.013). Genomic PBMCs-DNA methylation may be a useful epigenetic biomarker for early detection and cancer risk estimation. Impact: This study identifies a threshold for PBMCs-DNA methylation to detect cancer-affected from cancer-free subjects and an at-risk condition for cancer based on genomic DNA methylation and MTHFR677C>T-folate status.

Last Modified: 04/28/2017
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