Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts

被引：196

作者：

Fasanelli, Francesca ^{[1
,2
]}

Baglietto, Laura ^{[3
,4
,5
,6
]}

Ponzi, Erica ^{[1
]}

Guida, Florence ^{[7
]}

Campanella, Gianluca ^{[7
]}

Johansson, Mattias ^{[8
,9
]}

Grankvist, Kjell ^{[9
]}

Johansson, Mikael ^{[10
]}

Assumma, Manuela Bianca ^{[1
]}

Naccarati, Alessio ^{[1
]}

Chadeau-Hyam, Marc ^{[7
]}

Ala, Ugo ^{[11
]}

Faltus, Christian ^{[12
]}

Kaaks, Rudolf ^{[13
,14
]}

Risch, Angela ^{[12
,13
,14
,15
]}

De Stavola, Bianca ^{[16
]}

Hodge, Allison ^{[5
]}

Giles, Graham G. ^{[5
,6
]}

Southey, Melissa C. ^{[17
]}

Relton, Caroline L. ^{[18
]}

Haycock, Philip C. ^{[18
]}

Lund, Eiliv ^{[19
]}

Polidoro, Silvia ^{[1
]}

Sandanger, Torkjel M. ^{[19
]}

Severi, Gianluca ^{[1
,3
,4
,5
,6
]}

Vineis, Paolo ^{[1
,7
]}

机构：

[1] Human Genet Fdn, HuGeF, Mol End Epidemiol Unit, I-10126 Turin, Italy

[2] Univ Turin, Ctr Canc Prevent, Citta Salute & Sci Hosp, Canc Epidemiol Unit, I-10126 Turin, Italy

[3] Ctr Res Epidemiol & Populat Hlth, INSERM, U1018, Team 9, F-94805 Villejuif, France

[4] Paris South Univ, F-91450 Villejuif, France

[5] Canc Council Victoria, Canc Epidemiol Ctr, Dept Genet Epidemiol, Melbourne, Vic 3004, Australia

[6] Univ Melbourne, Ctr Epidemiol & Biostat, Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia

[7] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London W2 1PG, England

[8] Int Agcy Res Canc, Genet Epidemiol Div, F-69008 Lyon, France

[9] Umea Univ, Dept Biobank Res, SE-90187 Umea, Sweden

[10] Umea Univ, Dept Radiat Sci, SE-90187 Umea, Sweden

[11] Univ Turin, Dept Mol Biotechnol & Hlth Sci, I-10126 Turin, Italy

[12] DKFZ German Canc Res Ctr, Div Epigenom & Canc Risk Factors, D-69121 Heidelberg, Germany

[13] DKFZ German Canc Res Ctr, Div Canc Epidemiol, D-69121 Heidelberg, Germany

[14] Translat Lung Res Ctr Heidelberg, D-69120 Heidelberg, Germany

[15] Salzburg Univ, Div Canc Res & Epigenet, Dept Mol Biol, A-5020 Salzburg, Austria

[16] Univ London London Sch Hyg & Trop Med, Dept Med Stat, London WC1E 7HT, England

[17] Univ Melbourne, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia

[18] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England

[19] Arctic Univ Norway, Dept Community Med UiT, N-9019 Tromso, Norway

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

英国医学研究理事会;

关键词：

HYDROCARBON RECEPTOR REPRESSOR; DNA METHYLATION; CIGARETTE-SMOKING; F2RL3; METHYLATION; RISK; CESSATION; BIOMARKER; EXPOSURE; TIME; NORMALIZATION;

D O I：

10.1038/ncomms10192

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

DNA hypomethylation in certain genes is associated with tobacco exposure but it is unknown whether these methylation changes translate into increased lung cancer risk. In an epigenome-wide study of DNA from pre-diagnostic blood samples from 132 case-control pairs in the NOWAC cohort, we observe that the most significant associations with lung cancer risk are for cg05575921 in AHRR (OR for 1 s.d. = 0.37, 95% CI: 0.31-0.54, P-value = 3.3 x 10(-11)) and cg03636183 in F2RL3 (OR for 1 s.d. = 0.40, 95% CI: 0.31-0.56, P-value = 3.9 x 10(-10)), previously shown to be strongly hypomethylated in smokers. These associations remain significant after adjustment for smoking and are confirmed in additional 664 case-control pairs tightly matched for smoking from the MCCS, NSHDS and EPIC HD cohorts. The replication and mediation analyses suggest that residual confounding is unlikely to explain the observed associations and that hypomethylation of these CpG sites may mediate the effect of tobacco on lung cancer risk.

引用

页数：9

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