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

Francesca Fasanelli; Laura Baglietto; Erica Ponzi; Florence Guida; Gianluca Campanella; Mattias Johansson; Kjell Grankvist; Mikael Johansson; Manuela Bianca Assumma; Alessio Naccarati; Marc Chadeau-Hyam; Ugo Ala; Christian Faltus; Rudolf Kaaks; Angela Risch; Bianca De Stavola; Allison Hodge; Graham G. Giles; Melissa C. Southey; Caroline L. Relton; Philip C. Haycock; Eiliv Lund; Silvia Polidoro; Torkjel M. Sandanger; Gianluca Severi; Paolo Vineis

doi:10.1038/ncomms10192

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

Francesca Fasanelli, Laura Baglietto, Erica Ponzi, Florence Guida, Gianluca Campanella, Mattias Johansson, Kjell Grankvist, Mikael Johansson, Manuela Bianca Assumma, Alessio Naccarati, Marc Chadeau-Hyam, Ugo Ala, Christian Faltus, Rudolf Kaaks, Angela Risch, Bianca De Stavola, Allison Hodge, Graham G. Giles, Melissa C. Southey, Caroline L. ReltonPhilip C. Haycock, Eiliv Lund, Silvia Polidoro, Torkjel M. Sandanger, Gianluca Severi, Paolo Vineis

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Résumé

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 × 10 -11) and cg03636183 in F2RL3 (OR for 1 s.d.=0.40, 95% CI: 0.31-0.56, P-value=3.9 × 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.

langue originale	Anglais
Numéro d'article	10192
journal	Nature Communications
Volume	6
Les DOIs	https://doi.org/10.1038/ncomms10192
état	Publié - 15 déc. 2015

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10.1038/ncomms10192

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Fasanelli, F., Baglietto, L., Ponzi, E., Guida, F., Campanella, G., Johansson, M., Grankvist, K., Johansson, M., Assumma, M. B., Naccarati, A., Chadeau-Hyam, M., Ala, U., Faltus, C., Kaaks, R., Risch, A., De Stavola, B., Hodge, A., Giles, G. G., Southey, M. C., ... Vineis, P. (2015). Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts. Nature Communications, 6, Article 10192. https://doi.org/10.1038/ncomms10192

@article{f56caace91754356996e3347fe6fb1eb,

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

abstract = "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 × 10 -11) and cg03636183 in F2RL3 (OR for 1 s.d.=0.40, 95% CI: 0.31-0.56, P-value=3.9 × 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.",

author = "Francesca Fasanelli and Laura Baglietto and Erica Ponzi and Florence Guida and Gianluca Campanella and Mattias Johansson and Kjell Grankvist and Mikael Johansson and Assumma, {Manuela Bianca} and Alessio Naccarati and Marc Chadeau-Hyam and Ugo Ala and Christian Faltus and Rudolf Kaaks and Angela Risch and {De Stavola}, Bianca and Allison Hodge and Giles, {Graham G.} and Southey, {Melissa C.} and Relton, {Caroline L.} and Haycock, {Philip C.} and Eiliv Lund and Silvia Polidoro and Sandanger, {Torkjel M.} and Gianluca Severi and Paolo Vineis",

year = "2015",

month = dec,

day = "15",

doi = "10.1038/ncomms10192",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

}

Fasanelli, F, Baglietto, L, Ponzi, E, Guida, F, Campanella, G, Johansson, M, Grankvist, K, Johansson, M, Assumma, MB, Naccarati, A, Chadeau-Hyam, M, Ala, U, Faltus, C, Kaaks, R, Risch, A, De Stavola, B, Hodge, A, Giles, GG, Southey, MC, Relton, CL, Haycock, PC, Lund, E, Polidoro, S, Sandanger, TM, Severi, G & Vineis, P 2015, 'Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts', Nature Communications, VOL. 6, 10192. https://doi.org/10.1038/ncomms10192

TY - JOUR

T1 - Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts

AU - Fasanelli, Francesca

AU - Baglietto, Laura

AU - Ponzi, Erica

AU - Guida, Florence

AU - Campanella, Gianluca

AU - Johansson, Mattias

AU - Grankvist, Kjell

AU - Johansson, Mikael

AU - Assumma, Manuela Bianca

AU - Naccarati, Alessio

AU - Chadeau-Hyam, Marc

AU - Ala, Ugo

AU - Faltus, Christian

AU - Kaaks, Rudolf

AU - Risch, Angela

AU - De Stavola, Bianca

AU - Hodge, Allison

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - Relton, Caroline L.

AU - Haycock, Philip C.

AU - Lund, Eiliv

AU - Polidoro, Silvia

AU - Sandanger, Torkjel M.

AU - Severi, Gianluca

AU - Vineis, Paolo

PY - 2015/12/15

Y1 - 2015/12/15

N2 - 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 × 10 -11) and cg03636183 in F2RL3 (OR for 1 s.d.=0.40, 95% CI: 0.31-0.56, P-value=3.9 × 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.

AB - 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 × 10 -11) and cg03636183 in F2RL3 (OR for 1 s.d.=0.40, 95% CI: 0.31-0.56, P-value=3.9 × 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.

UR - http://www.scopus.com/inward/record.url?scp=84950107042&partnerID=8YFLogxK

U2 - 10.1038/ncomms10192

DO - 10.1038/ncomms10192

M3 - Article

C2 - 26667048

AN - SCOPUS:84950107042

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 10192

ER -