Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study

被引:164
作者
Ambatipudi, Srikant [1 ]
Cuenin, Cyrille [1 ]
Hernandez-Vargas, Hector [1 ]
Ghantous, Akram [1 ]
Le Calvez-Kelm, Florence [1 ]
Kaaks, Rudolf [2 ]
Barrdahl, Myrto [2 ]
Boeing, Heiner [3 ]
Aleksandrova, Krasimira [3 ]
Trichopoulou, Antonia [4 ,5 ]
Lagiou, Pagona [4 ,5 ]
Naska, Androniki [4 ,5 ]
Palli, Domenico [6 ]
Krogh, Vittorio [7 ]
Polidoro, Silvia [8 ]
Tumino, Rosario [9 ]
Panico, Salvatore [10 ]
Bueno-de-Mesquita, Bas [11 ,12 ,13 ,14 ]
Peeters, Petra H. M. [15 ,16 ]
Quiros, Jose Ramon [17 ]
Navarro, Carmen [18 ,19 ,20 ]
Ardanaz, Eva [19 ,21 ,22 ]
Dorronsoro, Miren [23 ]
Key, Tim [24 ]
Vineis, Paolo [25 ]
Murphy, Neil [25 ]
Riboli, Elio [25 ]
Romieu, Isabelle [1 ]
Herceg, Zdenko [1 ]
机构
[1] IARC, Lyon, France
[2] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
[3] German Inst Human Nutr Potsdam Rehbrcuke, Dept Epidemiol, Nuthetal, Germany
[4] Hellen Hlth Fdn, Athens, Greece
[5] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Nutr & Hlth,Unit Nutr Epide, GR-11527 Athens, Greece
[6] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy
[7] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy
[8] Human Genet Fdn HuGeF, Turin, Italy
[9] ASP Ragusa, Civ MP Arezzo Hosp, Canc Registry & Histopathol Unit, Rome, Italy
[10] Univ Naples Federico II, Dipartimento Med Clin & Chirurg, Naples, Italy
[11] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands
[12] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands
[13] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England
[14] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia
[15] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands
[16] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England
[17] Publ Hlth Directorate, Asturias, Spain
[18] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain
[19] CIBERESP, Murcia, Spain
[20] Univ Murcia, Dept Hlth & Social Sci, E-30001 Murcia, Spain
[21] Publ Hlth Inst Navarra, Pamplona, Spain
[22] Navarra Inst Hlth Res, IdiSNA, Pamplona, Spain
[23] Basque Reg Hlth Dept, Publ Hlth Direct & Biodonostia Ciberesp, San Sebastian, Spain
[24] Univ Oxford, Canc Epidemiol Unit, Oxford, England
[25] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England
关键词
DNA methylome; epigenetic signature; prospective cohort; tobacco smoking; CIGARETTE-SMOKING; MATERNAL SMOKING; CANCER; DISCOVERY; MICROARRAY; NUTRITION; BETA; REPLICATION; ENVIRONMENT; VARIABILITY;
D O I
10.2217/epi-2016-0001
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Aim: Epigenetic changes may occur in response to environmental stressors, and an altered epigenome pattern may represent a stable signature of environmental exposure. Materials & methods: Here, we examined the potential of DNA methylation changes in 910 prediagnostic peripheral blood samples as a marker of exposure to tobacco smoke in a large multinational cohort. Results: We identified 748 CpG sites that were differentially methylated between smokers and nonsmokers, among which we identified novel regionally clustered CpGs associated with active smoking. Importantly, we found a marked reversibility of methylation changes after smoking cessation, although specific genes remained differentially methylated up to 22 years after cessation. Conclusion: Our study has comprehensively cataloged the smoking-associated DNA methylation alterations and showed that these alterations are reversible after smoking cessation.
引用
收藏
页码:599 / 618
页数:20
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