Methylome analysis and epigenetic changes associated with menarcheal age.

TitleMethylome analysis and epigenetic changes associated with menarcheal age.
Publication TypeJournal Article
Year of Publication2013
AuthorsDemetriou CA, Chen J, Polidoro S, van Veldhoven K, Cuenin C, Campanella G, Brennan K, Clavel-Chapelon F, Dossus L, Kvaskoff M, Drogan D, Boeing H, Kaaks R, Risch A, Trichopoulos D, Lagiou P, Masala G, Sieri S, Tumino R, Panico S, Quirós RJ, Perez M-JSánchez, Amiano P, Castaño JMaría Hue, Ardanaz E, Onland-Moret C, Peeters P, Khaw K-T, Wareham N, Key TJ, Travis RC, Romieu I, Gallo V, Gunter M, Herceg Z, Kyriacou K, Riboli E, Flanagan JM, Vineis P
JournalPLoS One
Volume8
Issue11
Paginatione79391
Date Published2013
ISSN1932-6203
KeywordsAdult, Aged, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Humans, Menarche, Middle Aged, Prospective Studies
Abstract

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 (OR(12-14 vs. ≤11 yrs):1.78, 95%CI:1.01-3.17 and OR(≥15 vs. ≤11 yrs):4.59, 95%CI:2.04-10.33; P for trend<0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age.

DOI10.1371/journal.pone.0079391
Alternate JournalPLoS ONE
PubMed ID24278132
PubMed Central IDPMC3835804
Grant List14136 / / Cancer Research UK / United Kingdom
16491 / / Cancer Research UK / United Kingdom
G1000143 / / Medical Research Council / United Kingdom
/ / Cancer Research UK / United Kingdom
/ / Medical Research Council / United Kingdom