AHRR (cg05575921) hypomethylation marks smoking behaviour, morbidity and mortality
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- AHRR (cg05575921) hypomethylation marks smoking behaviour, morbidity and mortality
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RATIONALE AND OBJECTIVES: Self-reported smoking underestimates disease risk. Smoking affects DNA methylation, in particular the cg05575921 site in the aryl hydrocarbon receptor repressor (AHRR) gene. We tested the hypothesis that AHRR cg05575921 hypomethylation is associated with risk of smoking-related morbidity and mortality.
METHODS: From the Copenhagen City Heart Study representing the Danish general population, we studied 9234 individuals. Using bisulphite treated leucocyte DNA, AHRR (cg05575921) methylation was measured. Rs1051730 (CHRN3A) genotype was used to evaluate smoking heaviness. Participants were followed for up to 22 years for exacerbations of COPD, event of lung cancer and all-cause mortality. Six-year lung cancer risk was calculated according to the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCOM2012).
MEASUREMENTS AND MAIN RESULTS: AHRR (cg05575921) hypomethylation was associated with former and current smoking status, high daily and cumulative smoking, short time since smoking cessation (all p values <7×10-31), (-0.48% (1.48 (2.31 (4.3% (95% (p="2×10-7)," 0.0% 1.67 1.88) 10.3) 2.83 2576 3.7% 4.4%, 4.58 4.87 6 years 6-year 7.42) adjusted after all-cause among and by cancer chrn3a ci copd ct, cumulative eligible exacerbations, finally, for genotype high-risk highest hrs in incidences individuals lowest lung methylation mortality. multifactorially observed of p="0.77).</p" per plcom2012 predicted quintiles risks screening similar smokers smoking-related t-allele, the to versus were whereas>7×10-31),>
CONCLUSION: AHRR (cg05575921) hypomethylation, a marker of smoking behaviour, provides potentially clinical relevant predictions of future smoking-related morbidity and mortality.
|Number of pages||8|
|Publication status||Published - Jul 2017|
- Aged, Basic Helix-Loop-Helix Transcription Factors, Biomarkers, Cause of Death, DNA Methylation, Denmark, Disease Progression, Female, Genotype, Humans, Lung Neoplasms, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Receptors, Nicotinic, Repressor Proteins, Risk Assessment, Risk-Taking, Smoking, Journal Article
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