TY - JOUR
T1 - Methylome analysis and epigenetic changes associated with menarcheal age
AU - Demetriou, Christiana A.
AU - Chen, Jia
AU - Polidoro, Silvia
AU - Van Veldhoven, Karin
AU - Cuenin, Cyrille
AU - Campanella, Gianluca
AU - Brennan, Kevin
AU - Clavel-Chapelon, Françoise
AU - Dossus, Laure
AU - Kvaskoff, Marina
AU - Drogan, Dagmar
AU - Boeing, Heiner
AU - Kaaks, Rudolf
AU - Risch, Angela
AU - Trichopoulos, Dimitrios
AU - Lagiou, Pagona
AU - Masala, Giovanna
AU - Sieri, Sabina
AU - Tumino, Rosario
AU - Panico, Salvatore
AU - Ramón Quirós, J.
AU - Perez, María José Sánchez
AU - Amiano, Pilar
AU - Castaño, José María Huerta
AU - Ardanaz, Eva
AU - Onland-Moret, Charlotte
AU - Peeters, Petra
AU - Khaw, Kay Tee
AU - Wareham, Nick
AU - Key, Timothy J.
AU - Travis, Ruth C.
AU - Romieu, Isabelle
AU - Gallo, Valentina
AU - Gunter, Marc
AU - Herceg, Zdenko
AU - Kyriacou, Kyriacos
AU - Riboli, Elio
AU - Flanagan, James M.
AU - Vineis, Paolo
PY - 2013/11/20
Y1 - 2013/11/20
N2 - 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<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.
AB - 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<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.
UR - http://www.scopus.com/inward/record.url?scp=84894263959&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0079391
DO - 10.1371/journal.pone.0079391
M3 - Article
C2 - 24278132
AN - SCOPUS:84894263959
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e79391
ER -
