PMID- 32321578 OWN - NLM STAT- MEDLINE DCOM- 20210603 LR - 20240329 IS - 1868-7083 (Electronic) IS - 1868-7075 (Print) IS - 1868-7075 (Linking) VI - 12 IP - 1 DP - 2020 Apr 22 TI - Epigenetic prediction of complex traits and mortality in a cohort of individuals with oropharyngeal cancer. PG - 58 LID - 10.1186/s13148-020-00850-4 [doi] LID - 58 AB - BACKGROUND: DNA methylation (DNAm) variation is an established predictor for several traits. In the context of oropharyngeal cancer (OPC), where 5-year survival is ~ 65%, DNA methylation may act as a prognostic biomarker. We examined the accuracy of DNA methylation biomarkers of 4 complex exposure traits (alcohol consumption, body mass index [BMI], educational attainment and smoking status) in predicting all-cause mortality in people with OPC. RESULTS: DNAm predictors of alcohol consumption, BMI, educational attainment and smoking status were applied to 364 individuals with OPC in the Head and Neck 5000 cohort (HN5000; 19.6% of total OPC cases in the study), followed up for median 3.9 years; inter-quartile range (IQR) 3.3 to 5.2 years (time-to-event-death or censor). The proportion of phenotypic variance explained in each trait was as follows: 16.5% for alcohol consumption, 22.7% for BMI, 0.4% for educational attainment and 51.1% for smoking. We then assessed the relationship between each DNAm predictor and all-cause mortality using Cox proportional-hazard regression analysis. DNAm prediction of smoking was most consistently associated with mortality risk (hazard ratio [HR], 1.38 per standard deviation (SD) increase in smoking DNAm score; 95% confidence interval [CI] 1.04 to 1.83; P 0.025, in a model adjusted for demographic, lifestyle, health and biological variables). Finally, we examined the accuracy of each DNAm predictor of mortality. DNAm predictors explained similar levels of variance in mortality to self-reported phenotypes. Receiver operator characteristic (ROC) curves for the DNAm predictors showed a moderate discrimination of alcohol consumption (area under the curve [AUC] 0.63), BMI (AUC 0.61) and smoking (AUC 0.70) when predicting mortality. The DNAm predictor for education showed poor discrimination (AUC 0.57). Z tests comparing AUCs between self-reported phenotype ROC curves and DNAm score ROC curves did not show evidence for difference between the two (alcohol consumption P 0.41, BMI P 0.62, educational attainment P 0.49, smoking P 0.19). CONCLUSIONS: In the context of a clinical cohort of individuals with OPC, DNAm predictors for smoking, alcohol consumption, educational attainment and BMI exhibit similar predictive values for all-cause mortality compared to self-reported data. These findings may have translational utility in prognostic model development, particularly where phenotypic data are not available. FAU - Langdon, Ryan J AU - Langdon RJ AD - MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. AD - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. FAU - Beynon, Rhona A AU - Beynon RA AD - MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. AD - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. FAU - Ingarfield, Kate AU - Ingarfield K AD - NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and University of Bristol, Bristol, UK. AD - Centre for Trials Research, Neuadd Meirionnydd, Heath Park Way, Cardiff, UK. AD - Community Oral Health, University of Glasgow Dental School, Sauchiehall Street, Glasgow, UK. FAU - Marioni, Riccardo E AU - Marioni RE AD - MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, Scotland, EH4 2XU, UK. AD - Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. FAU - McCartney, Daniel L AU - McCartney DL AD - MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, Scotland, EH4 2XU, UK. AD - Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. FAU - Martin, Richard M AU - Martin RM AD - MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. AD - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. AD - NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and University of Bristol, Bristol, UK. FAU - Ness, Andy R AU - Ness AR AD - NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and University of Bristol, Bristol, UK. FAU - Pawlita, Michael AU - Pawlita M AD - Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Waterboer, Tim AU - Waterboer T AD - Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Relton, Caroline AU - Relton C AD - MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. AD - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. AD - NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and University of Bristol, Bristol, UK. FAU - Thomas, Steven J AU - Thomas SJ AD - NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and University of Bristol, Bristol, UK. FAU - Richmond, Rebecca C AU - Richmond RC AD - MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. rebecca.richmond@bristol.ac.uk. AD - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. rebecca.richmond@bristol.ac.uk. LA - eng GR - MC_UU_00011/5/MRC_/Medical Research Council/United Kingdom GR - MC_UU_12013/3/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00011/1/MRC_/Medical Research Council/United Kingdom GR - C18281/A20988/CRUK_/Cancer Research UK/United Kingdom GR - 25350/CRUK_/Cancer Research UK/United Kingdom GR - WT099874MA/WT_/Wellcome Trust/United Kingdom GR - C18281/A19169/CRUK_/Cancer Research UK/United Kingdom GR - 15954/CRUK_/Cancer Research UK/United Kingdom GR - MC_UU_12013/2/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - MC_UU_12013/1/MRC_/Medical Research Council/United Kingdom GR - 19169/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20200422 PL - Germany TA - Clin Epigenetics JT - Clinical epigenetics JID - 101516977 RN - 0 (Biomarkers, Tumor) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Alcohol Drinking/adverse effects/*epidemiology/genetics MH - Biomarkers, Tumor/*genetics MH - Body Mass Index MH - Cohort Studies MH - *DNA Methylation MH - Educational Status MH - Epigenesis, Genetic MH - Female MH - Humans MH - Male MH - Middle Aged MH - Oropharyngeal Neoplasms/etiology/genetics/*mortality MH - Prognosis MH - ROC Curve MH - Risk Assessment MH - Tobacco Smoking/adverse effects/*epidemiology/genetics PMC - PMC7178612 COIS- The authors have no competing interests to declare. EDAT- 2020/04/24 06:00 MHDA- 2021/06/04 06:00 PMCR- 2020/04/22 CRDT- 2020/04/24 06:00 PHST- 2020/01/05 00:00 [received] PHST- 2020/04/08 00:00 [accepted] PHST- 2020/04/24 06:00 [entrez] PHST- 2020/04/24 06:00 [pubmed] PHST- 2021/06/04 06:00 [medline] PHST- 2020/04/22 00:00 [pmc-release] AID - 10.1186/s13148-020-00850-4 [pii] AID - 850 [pii] AID - 10.1186/s13148-020-00850-4 [doi] PST - epublish SO - Clin Epigenetics. 2020 Apr 22;12(1):58. doi: 10.1186/s13148-020-00850-4.