Epigenetic prediction of complex traits and mortality in a cohort of individuals with oropharyngeal cancer

Ryan J Langdon, Rhona A Beynon, Kate Ingarfield, Riccardo E. Marioni, Daniel M MacCartney, Richard M Martin, Andy R Ness, Michael Pawlita, Tim Waterboer, Caroline Relton, Steven J Thomas, Rebecca C Richmond

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Abstract

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: 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-hazards regression analysis. Only DNAm prediction of smoking was associated with mortality risk (hazard ratio [HR]: 1.36 per standard deviation (SD) increase in smoking DNAm score; 95% confidence interval [CI]: 1.02 to 1.82; P: 0.034, 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.
Original languageEnglish
Article number58 (2020)
Number of pages14
JournalClinical Epigenetics
Volume12
DOIs
Publication statusPublished - 22 Apr 2020

Structured keywords

  • ICEP
  • Bristol Population Health Science Institute

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  • Projects

    IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

    Gaunt, L. F. & Davey Smith, G.

    1/04/1831/03/23

    Project: Research

    Rework of IEU 2 Relton Programme

    Relton, C. L.

    1/04/1831/03/23

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