Methylome Analysis and Epigenetic Changes Associated with Menarcheal Age

被引：29

作者：

Demetriou, Christiana A. ^{[1
,2
]}

Chen, Jia ^{[3
,4
,5
]}

Polidoro, Silvia ^{[6
]}

van Veldhoven, Karin ^{[2
]}

Cuenin, Cyrille ^{[7
]}

Campanella, Gianluca ^{[2
]}

Brennan, Kevin ^{[8
]}

Clavel-Chapelon, Francoise ^{[9
,10
]}

Dossus, Laure ^{[9
,10
]}

Kvaskoff, Marina ^{[9
,10
]}

Drogan, Dagmar ^{[11
]}

Boeing, Heiner ^{[11
]}

Kaaks, Rudolf ^{[12
]}

Risch, Angela ^{[13
]}

Trichopoulos, Dimitrios ^{[14
,15
,16
]}

Lagiou, Pagona ^{[14
,15
,17
]}

Masala, Giovanna ^{[18
]}

Sieri, Sabina ^{[19
]}

Tumino, Rosario ^{[20
,21
]}

Panico, Salvatore ^{[22
]}

Ramon Quiros, J. ^{[23
]}

Sanchez Perez, Maria-Jose ^{[24
,25
]}

Amiano, Pilar ^{[25
,26
]}

Huerta Castano, Jose Maria ^{[25
,27
]}

Ardanaz, Eva ^{[25
,28
]}

Onland-Moret, Charlotte ^{[29
]}

Peeters, Petra ^{[29
]}

Khaw, Kay-Tee ^{[30
]}

Wareham, Nick ^{[30
]}

Key, Timothy J. ^{[31
]}

Travis, Ruth C. ^{[31
]}

Romieu, Isabelle ^{[32
]}

Gallo, Valentina ^{[2
,33
]}

Gunter, Marc ^{[2
]}

Herceg, Zdenko ^{[6
]}

Kyriacou, Kyriacos ^{[1
]}

Riboli, Elio ^{[34
]}

Flanagan, James M. ^{[8
]}

Vineis, Paolo ^{[2
]}

机构：

[1] Cyprus Inst Neurol & Genet, Dept Electron Microscopy & Mol Pathol, Nicosia, Cyprus

[2] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[3] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA

[4] Mt Sinai Sch Med, Dept Paediat, New York, NY USA

[5] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA

[6] Human Genet Fdn, Mol & Genet Epidemiol Unit, Turin, Italy

[7] Int Agcy Res Canc, Epigenet Grp, F-69372 Lyon, France

[8] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Epigenet Unit, London, England

[9] Inst Gustave Roussy, INSERM, Ctr Res Epidemiol & Populat Hlth, F-94805 Villejuif, France

[10] Paris South Univ, Nutr Hormones & Canc Unit, Villejuif, France

[11] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany

[12] German Canc Res Ctr, Dept Canc Epidemiol, Heidelberg, Germany

[13] German Canc Res Ctr, Dept Epigen & Canc Risk Factors, Heidelberg, Germany

[14] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[15] Acad Athens, Bur Epidemiol Res, Athens, Greece

[16] Hellen Hlth Fdn, Athens, Greece

[17] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Food & Nutr Policies, GR-11527 Athens, Greece

[18] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy

[19] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy

[20] ASP Ragusa, Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy

[21] ASP Ragusa, Civile MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy

[22] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy

[23] Publ Hlth & Planning Directorate, Asturias, Spain

[24] Andalusian Sch Publ Hlth, Granada, Spain

[25] CIBERESP, Madrid, Spain

[26] BioDonostia Res Inst, Hlth Dept Basque Reg, Publ Hlth Div Gipuzkoa, San Sebastian, Spain

[27] Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain

[28] Navarre Publ Hlth Inst, Pamplona, Spain

[29] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[30] Cambridge Inst Publ Hlth, MRC Epidemiol Unit, Cambridge, England

[31] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England

[32] Int Agcy Res Canc, Nutr & Metab Sect, F-69372 Lyon, France

[33] Univ London, Barts & London Sch Med, Ctr Primary Care & Publ Hlth, London, England

[34] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England

来源：

PLOS ONE | 2013年 / 8卷 / 11期

基金：

英国医学研究理事会;

关键词：

GENOMIC DNA HYPOMETHYLATION; BREAST-CANCER; METHYLATION PATTERNS; COLORECTAL ADENOMA; LEUKOCYTE DNA; BLOOD-CELLS; RISK; IMPACT; LUMA; HYPERMETHYLATION;

D O I：

10.1371/journal.pone.0079391

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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