Methylome analysis and epigenetic changes associated with menarcheal age

Christiana A. Demetriou, Jia Chen, Silvia Polidoro, Karin Van Veldhoven, Cyrille Cuenin, Gianluca Campanella, Kevin Brennan, Françoise Clavel-Chapelon, Laure Dossus, Marina Kvaskoff, Dagmar Drogan, Heiner Boeing, Rudolf Kaaks, Angela Risch, Dimitrios Trichopoulos, Pagona Lagiou, Giovanna Masala, Sabina Sieri, Rosario Tumino, Salvatore PanicoJ. Ramón Quirós, María José Sánchez Perez, Pilar Amiano, José María Huerta Castaño, Eva Ardanaz, Charlotte Onland-Moret, Petra Peeters, Kay Tee Khaw, Nick Wareham, Timothy J. Key, Ruth C. Travis, Isabelle Romieu, Valentina Gallo, Marc Gunter, Zdenko Herceg, Kyriacos Kyriacou, Elio Riboli, James M. Flanagan, Paolo Vineis

Research output: Contribution to journalArticlepeer-review


Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR:1.32, 95%CI:1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR12-14vs.≤11 yrs:1.78, 95%CI:1.01-3.17 and OR≥15vs.≤11 yrs:4.59, 95%CI:2.04-10.33; P for trend

Original languageEnglish
Article numbere79391
JournalPLoS One
Issue number11
Publication statusPublished - Nov 20 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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