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

• DOI: 10.1038/ncomms10192
• Publication Date: 2015-12-15T10:21:45Z
• Authors: Francesca Fasanelli; Laura Baglietto; Erica Ponzi; Florence Guida; Gianluca Campanella; Mattias Johansson; Kjell Grankvist; Mikael Johansson; Manuela Bianca As...; 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
• Keywords: CpG site; Epigenome

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