Journal article
Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts
F Fasanelli, L Baglietto, E Ponzi, F Guida, G Campanella, M Johansson, K Grankvist, M Johansson, MB Assumma, A Naccarati, M Chadeau-Hyam, U Ala, C Faltus, R Kaaks, A Risch, B De Stavola, A Hodge, GG Giles, MC Southey, CL Relton Show all
Nature Communications | NATURE PORTFOLIO | Published : 2015
DOI: 10.1038/ncomms10192
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-..
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Awarded by Bundesministerium für Bildung und Forschung
Funding Acknowledgements
The NOWAC postgenome cohort study has been funded by the ERC advanced grant 'Transcriptomics in Cancer Epidemiology-ERC-2008-AdG-232997'. The methylation analyses for the NOWAC cohort were performed at the Human Genetics Foundation in Torino, Italy with funds from Compagnia di San Paolo. The MCCS nested case-control study of methylation and lung cancer risk was funded by a grant from the Australian National Health and Medical Research Council (Project Grant #1050198). For the MCCS, we acknowledge the contribution of Dr Chol-hee Jung and Dr Jessica Chung from the Life Sciences Computation Centre and the Victorian Life Sciences Computation Initiative in Melbourne for the preparation of the bioinformatics pipeline and Drs Ming Wong and Jihoon Joo for their contribution to the methylation analyses conducted in the Genetic Epidemiology Laboratory, Department of Pathology, the University of Melbourne. The NSHDS nested case-control study of methylation and lung cancer risk was funded by a grant from the Roy Castle Lung Cancer Foundation and supported by the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013_2). We are indebted to the laboratory and bioinformatics team (Dr Wendy McArdle, Dr Nabila Kazmi, Dr Hashem Shihab and Dr Tom Gaunt) for their contribution to the generation of the Illumina Infiumiun HumanMethylation450 data for this analysis. The EPIC-Heidelberg cohort study was conducted with the financial support of the 'Europe Against Cancer' program of the European Commission (SANCO), the German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research (BMBF). The present nested case-control study of methylation and lung cancer risk was supported by the German Center for Lung Research (DZL), grant PB13394. L.B. is supported by a Marie Curie International Incoming Fellowship within the 7th European Community Framework Programme.