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Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk
Author(s) -
Guarini Patrizia,
Udali Silvia,
Pattini Patrizia,
Moruzzi Sara,
Girelli Domenico,
Pizzolo Francesca,
Martinelli Nicola,
Olivieri Oliviero,
Choi Sang Woon,
Friso Simonetta
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.248.1
Subject(s) - dna methylation , epigenetics , methylation , biomarker , peripheral blood mononuclear cell , cancer , cancer research , biology , medicine , microbiology and biotechnology , oncology , dna , immunology , gene , genetics , gene expression , in vitro
DNA methylation is a reversible epigenetic phenomenon that can be modified by nutrients such as folate and influenced by the MTHFR677C>;T polymorphism in a gene‐nutrient interaction manner. In human cancer, global DNA hypomethylation is an almost universal finding. Peripheral blood mononuclear cells (PBMCs) are easily accessible in humans and our aim was to test PBMCs DNA methylation according to the folate‐ MTHFR677C>;T polymorphism interaction, as a potential biomarker for cancer risk. Global DNA methylation was measured in PBMCs of 68 subjects with cancer history at enrollment and 62 with cancer after eight‐year follow‐up compared to age‐and sex‐matched controls (68 at enrollment, 58 at follow‐up). Cancer subjects had lower plasma folate concentrations ( P =0.003), higher frequency of MTHFR677TT ( P =0.013) and lower PBMCs‐ DNA methylation than controls ( P <0.0001). A DNA methylation threshold of 4.74% categorized cancer patients from controls. Subjects with cancer at follow‐up had at enrollment lower DNA methylation than controls ( P <0.0001). The association of MTHFR677TT and low plasma folate showed the lowest DNA methylation levels (4.39%). Cancer deaths had a lower DNA methylation compared with other cause deaths ( P =0.015) and the survivors had an increased DNA methylation compared to cancer ( P =0.004). Low global DNA methylation in PBMCs may be a useful predictive biomarker of cancer.