biostudies-literatureTeschendorff AEPublic Health AgencyNCI NIH HHSWellcome Trust440-6https://www.ebi.ac.uk/biostudies/studies/S-EPMC2847747biostudies-literatureUnknown20(4)Polycomb group proteins (PCGs) are involved in repression of genes that are required for stem cell differentiation. Recently, it was shown that promoters of PCG target genes (PCGTs) are 12-fold more likely to be methylated in cancer than non-PCGTs. Age is the most important demographic risk factor for cancer, and we hypothesized that its carcinogenic potential may be referred by irreversibly stabilizing stem cell features. To test this, we analyzed the methylation status of over 27,000 CpGs mapping to promoters of approximately 14,000 genes in whole blood samples from 261 postmenopausal women. We demonstrate that stem cell PCGTs are far more likely to become methylated with age than non-targets (odds ratio = 5.3 [3.8-7.4], P < 10(-10)), independently of sex, tissue type, disease state, andGenome researchAge-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer.PMC2847747R01-CA096958STL/3714/07R01 CA096958R01 CA075090Kocjan GBeck SSavage DAGayther SAMaxwell APJacobs IJJones AShen HNoushmehr HMenon UWidschwendter MWagner WLaird PWMarth CCampan MRamus SJBell CGMueller-Holzner EGentry-Maharaj ATeschendorff AEWeisenberger DJfalseAge-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer.Polycomb group proteins (PCGs) are involved in repression of genes that are required for stem cell differentiation. Recently, it was shown that promoters of PCG target genes (PCGTs) are 12-fold more likely to be methylated in cancer than non-PCGTs. Age is the most important demographic risk factor for cancer, and we hypothesized that its carcinogenic potential may be referred by irreversibly stabilizing stem cell features. To test this, we analyzed the methylation status of over 27,000 CpGs mapping to promoters of approximately 14,000 genes in whole blood samples from 261 postmenopausal women. We demonstrate that stem cell PCGTs are far more likely to become methylated with age than non-targets (odds ratio = 5.3 [3.8-7.4], P < 10(-10)), independently of sex, tissue type, disease state, and2010-01-01T00:00:00Z2010 Apr2025-04-03T22:16:19.201Z2019-06-06T21:58:25ZS-EPMC28477472021994410.1101/gr.103606.109