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Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer

By Ryan Langdon, Rebecca Richmond, Hannah R Elliott, Tom Dudding, Nabila Kazmi, Chris Penfold, Kate Ingarfield, Karen Ho, Andrew Bretherick, Chris Haley, Yanni Zeng, Rosie M Walker, Michael Pawlita, Tim Waterboer, Sue Ring, Tom Gaunt, George Davey Smith, Matthew Suderman, Steve Thomas, Andy Ness, Caroline Relton

Posted 28 Jun 2019
bioRxiv DOI: 10.1101/679316

Smoking status, alcohol consumption and HPV infection (acquired through sexual activity) are the predominant risk factors for oropharyngeal cancer and are thought to alter the prognosis of the disease. Here, we conduct epigenome-wide association studies (EWAS) of these factors and ∼3-year survival using Illumina Methylation EPIC blood DNA methylation profiles from 409 individuals in the Head and Neck 5000 (HN5000) study. CpG site associations below our multiple-testing threshold ( P Bonferroni < 0.05) with both a prognostic factor and with survival were observed in four gene regions: SPEG (smoking), GFI1 (smoking), PPT2 (smoking), and KHD3CL (alcohol consumption). These were further analysed using 2-step Mendelian randomization to assess whether methylation may be a causal mediator of cancer survival. Evidence for mediation was observed only in the SPEG gene region, showing an association with decreased survival (mortality HR: 1.28, 95% CI: 1.14 to 1.43, P: 2.12×10−05). Replication in data from independent datasets, and from HN5000 participants with longer follow-up times is needed to confirm these findings.

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