DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

被引：137

作者：

Ambatipudi, Srikant ^{[1
]}

Horvath, Steve ^{[2
]}

Perrier, Flavie ^{[1
]}

Cuenin, Cyrille ^{[1
]}

Hernandez-Vargas, Hector ^{[1
]}

Le Calvez-Kelm, Florence ^{[1
]}

Durand, Geoffroy ^{[1
]}

Byrnes, Graham ^{[1
]}

Ferrari, Pietro ^{[1
]}

Bouaoun, Liacine ^{[1
]}

Sklias, Athena ^{[1
]}

Chajes, Veronique ^{[1
]}

Overvad, Kim ^{[3
]}

Seven, Gianluca ^{[4
,5
,6
,7
]}

Baglietto, Laura ^{[4
,6
,7
]}

Clavel-Chapelon, Francoise ^{[4
]}

Kaaks, Rudolf ^{[8
]}

Barrdahl, Myrto ^{[8
]}

Boeing, Heiner ^{[9
]}

Trichopoulou, Antonia ^{[10
,11
]}

Lagiou, Pagona ^{[10
,11
,12
]}

Naska, Androniki ^{[10
,11
]}

Masala, Giovanna ^{[13
]}

Agnoli, Claudia ^{[14
]}

Polidoro, Silvia ^{[5
]}

Tumino, Rosario ^{[15
,16
]}

Panico, Salvatore ^{[17
]}

Dolle, Martijn ^{[18
]}

Peeters, Petra H. M. ^{[19
,20
]}

Onland-Moret, N. Charlotte ^{[19
]}

Sandanger, Torkjel M. ^{[21
]}

Nost, Therese H. ^{[21
]}

Weiderpass, Elisabete ^{[21
,22
,23
,24
]}

Quiros, J. Ramon ^{[25
]}

Agudo, Antonio ^{[26
]}

Rodriguez-Barranco, Miguel ^{[27
,28
]}

Castano, Jose Maria Huerta ^{[28
,29
]}

Barricarte, Aurelio ^{[28
,30
,31
]}

Fernandez, Ander Matheu ^{[32
,33
]}

Travis, Ruth C. ^{[34
]}

Vineis, Paolo ^{[35
]}

Muller, David C. ^{[35
]}

Riboli, Elio ^{[35
]}

Gunter, Marc ^{[1
]}

Romieu, Isabelle ^{[1
]}

Herceg, Zdenko ^{[1
]}

机构：

[1] IARC, Lyon, France

[2] Univ Calif Los Angeles, Human Genet & Biostat, Los Angeles, CA 90095 USA

[3] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, Aarhus, Denmark

[4] Univ Paris Sud, INSERM, Ctr Rech Epidemiol & Sante Populat, CESP,U1018,Univ Paris Saclay,UVSQ,Inst Gustave Ro, Villejuif, France

[5] Human Genet Fdn HuGeF, Turin, Italy

[6] Univ Melbourne, Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic, Australia

[7] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia

[8] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

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

[10] Hellen Hlth Fdn, Athens, Greece

[11] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Nutr & Hlth,Unit Nutr Epide, Athens, Greece

[12] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

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

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

[15] Civ MP Arezzo, ASP Ragusa, Canc Registry, Ragusa, Italy

[16] Civ MP Arezzo, ASP Ragusa, Histopathol Unit, Ragusa, Italy

[17] Univ Naples Federico II, Dipartimento Med Clin & Chirurg, Naples, Italy

[18] Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, Bilthoven, Netherlands

[19] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands

[20] Imperial Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England

[21] Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway

[22] Inst Populat Based Canc Res, Canc Registry Norway, Dept Res, Oslo, Norway

[23] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[24] Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland

[25] Publ Hlth Directorate, Asturias, Spain

[26] Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Program, Unit Nutr & Canc, Barcelona, Spain

[27] Univ Granada, Hospit Univ Granada, Inst Invest Biosanitaria Ibsn Granada, Escuela Andaluza Salud Publ, Granada, Spain

[28] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain

[29] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain

[30] Navarra Publ Hlth Inst, Pamplona, Spain

[31] Navarra Inst Hlth Res IdiSNA, Pamplona, Spain

[32] Biodonostia Hlth Res Inst, Cellular Oncol Grp, Paseo Dr Beguiristain S-N, San Sebastian, Spain

[33] Basque Fdn, Ikerbasque, Bilbao, Spain

[34] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England

[35] Imperial Coll London, Sch Publ Hlth, London, England

来源：

EUROPEAN JOURNAL OF CANCER | 2017年 / 75卷

关键词：

DNA methylation; Epigenomics; Age acceleration; Breast cancer; Biomarkers; Prospective studies; PERIPHERAL-BLOOD; METHYLATION AGE; MORTALITY; CLOCK; HYPERMETHYLATION; POPULATION; BIOLOGY; DRIFT; BETA; LUMA;

D O I：

10.1016/j.ejca.2017.01.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aim of the study: A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. Methods: Here, we profiled DNA methylation changes in a nested case control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. Results: We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007-1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007-1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020-1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03-1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. Conclusion: Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：299 / 307

页数：9

共 46 条

[1] Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study [J].

Ambatipudi, Srikant ;

Cuenin, Cyrille ;

Hernandez-Vargas, Hector ;

Ghantous, Akram ;

Le Calvez-Kelm, Florence ;

Kaaks, Rudolf ;

Barrdahl, Myrto ;

Boeing, Heiner ;

Aleksandrova, Krasimira ;

Trichopoulou, Antonia ;

Lagiou, Pagona ;

Naska, Androniki ;

Palli, Domenico ;

Krogh, Vittorio ;

Polidoro, Silvia ;

Tumino, Rosario ;

Panico, Salvatore ;

Bueno-de-Mesquita, Bas ;

Peeters, Petra H. M. ;

Quiros, Jose Ramon ;

Navarro, Carmen ;

Ardanaz, Eva ;

Dorronsoro, Miren ;

Key, Tim ;

Vineis, Paolo ;

Murphy, Neil ;

Riboli, Elio ;

Romieu, Isabelle ;

Herceg, Zdenko .

EPIGENOMICS, 2016, 8 (05) :599-618

[2] Impact of aging on the biology of breast cancer [J].

Benz, Christopher C. .

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2008, 66 (01) :65-74

[3] High density DNA methylation array with single CpG site resolution [J].

Bibikova, Marina ;

Barnes, Bret ;

Tsan, Chan ;

Ho, Vincent ;

Klotzle, Brandy ;

Le, Jennie M. ;

Delano, David ;

Zhang, Lu ;

Schroth, Gary P. ;

Gunderson, Kevin L. ;

Fan, Jian-Bing ;

Shen, Richard .

GENOMICS, 2011, 98 (04) :288-295

[4] Diet and cancer - The European prospective investigation into cancer and nutrition [J].

Bingham, S ;

Riboli, E .

NATURE REVIEWS CANCER, 2004, 4 (03) :206-215

[5] Why men age faster but reproduce longer than women: mTOR and evolutionary perspectives [J].

Blagosklonny, Mikhail V. .

AGING-US, 2010, 2 (05) :265-273

[6] Frailty is associated with the epigenetic clock but not with telomere length in a German cohort [J].

Breitling, Lutz Philipp ;

Saum, Kai-Uwe ;

Perna, Laura ;

Schoettker, Ben ;

Holleczek, Bernd ;

Brenner, Hermann .

CLINICAL EPIGENETICS, 2016, 8 :1-8

[7] DNA methylation-based measures of biological age: meta-analysis predicting time to death [J].

Chen, Brian H. ;

Marioni, Riccardo E. ;

Colicino, Elena ;

Peters, Marjolein J. ;

Ward-Caviness, Cavin K. ;

Tsai, Pei-Chien ;

Roetker, Nicholas S. ;

Just, Allan C. ;

Demerath, Ellen W. ;

Guan, Weihua ;

Bressler, Jan ;

Fornage, Myriam ;

Studenski, Stephanie ;

Vandiver, Amy R. ;

Moore, Ann Zenobia ;

Tanaka, Toshiko ;

Kiel, Douglas P. ;

Liang, Liming ;

Vokonas, Pantel ;

Schwartz, Joel ;

Lunetta, Kathryn L. ;

Murabito, Joanne M. ;

Bandinelli, Stefania ;

Hernandez, Dena G. ;

Melzer, David ;

Nalls, Michael ;

Pilling, Luke C. ;

Price, Timothy R. ;

Singleton, Andrew B. ;

Gieger, Christian ;

Holle, Rolf ;

Kretschmer, Anja ;

Kronenberg, Florian ;

Kunze, Sonja ;

Linseisen, Jakob ;

Meisinger, Christine ;

Rathmann, Wolfgang ;

Waldenberger, Melanie ;

Visscher, Peter M. ;

Shah, Sonia ;

Wray, Naomi R. ;

McRae, Allan F. ;

Franco, Oscar H. ;

Hofman, Albert ;

Uitterlinden, Andre G. ;

Absher, Devin ;

Assimes, Themistocles ;

Levine, Morgan E. ;

Lu, Ake T. ;

Tsao, Philip S. .

AGING-US, 2016, 8 (09) :1844-1865

[8] Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray [J].

Chen, Yi-an ;

Lemire, Mathieu ;

Choufani, Sanaa ;

Butcher, Darci T. ;

Grafodatskaya, Daria ;

Zanke, Brent W. ;

Gallinger, Steven ;

Hudson, Thomas J. ;

Weksberg, Rosanna .

EPIGENETICS, 2013, 8 (02) :203-209

[9] DNA methylation age is associated with mortality in a longitudinal Danish twin study [J].

Christiansen, Lene ;

Lenart, Adam ;

Tan, Qihua ;

Vaupel, James W. ;

Aviv, Abraham ;

McGue, Matt ;

Christensen, Kaare .

AGING CELL, 2016, 15 (01) :149-154

[10] Identifying the genomic determinants of aging and longevity in human population studies: Progress and challenges [J].

Deelen, Joris ;

Beekman, Marian ;

Capri, Miriam ;

Franceschi, Claudio ;

Slagboom, P. Eline .

BIOESSAYS, 2013, 35 (04) :386-396

← 1 2 3 4 5 →