Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer.
Adult
Alcohol Drinking
/ adverse effects
Biomarkers
/ analysis
Case-Control Studies
Cohort Studies
CpG Islands
/ genetics
DNA Methylation
Epigenesis, Genetic
/ genetics
Epigenome
/ genetics
Epigenomics
/ methods
Female
Humans
Male
Mendelian Randomization Analysis
/ methods
Middle Aged
Muscle Proteins
/ genetics
Oncogene Proteins, Viral
/ blood
Oropharyngeal Neoplasms
/ etiology
Papillomavirus Infections
/ complications
Prognosis
Protein Serine-Threonine Kinases
/ genetics
Proteins
/ genetics
Repressor Proteins
/ blood
Risk Factors
Smoking
/ adverse effects
Survival Rate
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
29 06 2020
29 06 2020
Historique:
received:
10
01
2020
accepted:
19
05
2020
entrez:
1
7
2020
pubmed:
1
7
2020
medline:
19
8
2021
Statut:
epublish
Résumé
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 conducted single-site and differentially methylated region (DMR) epigenome-wide association studies (EWAS) of these factors, in addition to ∼ 3-year survival, using Illumina Methylation EPIC DNA methylation profiles from whole blood in 409 individuals as part of the Head and Neck 5000 (HN5000) study. Overlapping sites between each factor and survival were then assessed using two-step Mendelian randomization to assess whether methylation at these positions causally affected survival. Using the MethylationEPIC array in an OPC dataset, we found novel CpG associations with smoking, alcohol consumption and ~ 3-year survival. We found no CpG associations below our multiple testing threshold associated with HPV16 E6 serological response (used as a proxy for HPV infection). CpG site associations below our multiple-testing threshold (P Part of the effect of smoking on survival in those with oropharyngeal cancer may be mediated by methylation at the SPEG gene locus. Replication in data from independent datasets and data from HN5000 with longer follow-up times is needed to confirm these findings.
Sections du résumé
BACKGROUND
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 conducted single-site and differentially methylated region (DMR) epigenome-wide association studies (EWAS) of these factors, in addition to ∼ 3-year survival, using Illumina Methylation EPIC DNA methylation profiles from whole blood in 409 individuals as part of the Head and Neck 5000 (HN5000) study. Overlapping sites between each factor and survival were then assessed using two-step Mendelian randomization to assess whether methylation at these positions causally affected survival.
RESULTS
Using the MethylationEPIC array in an OPC dataset, we found novel CpG associations with smoking, alcohol consumption and ~ 3-year survival. We found no CpG associations below our multiple testing threshold associated with HPV16 E6 serological response (used as a proxy for HPV infection). CpG site associations below our multiple-testing threshold (P
CONCLUSIONS
Part of the effect of smoking on survival in those with oropharyngeal cancer may be mediated by methylation at the SPEG gene locus. Replication in data from independent datasets and data from HN5000 with longer follow-up times is needed to confirm these findings.
Identifiants
pubmed: 32600451
doi: 10.1186/s13148-020-00870-0
pii: 10.1186/s13148-020-00870-0
pmc: PMC7322918
doi:
Substances chimiques
Biomarkers
0
E6 protein, Human papillomavirus type 16
0
KHDC3L protein, human
0
Muscle Proteins
0
Oncogene Proteins, Viral
0
Proteins
0
Repressor Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
SPEG protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
95Subventions
Organisme : Medical Research Council
ID : MC_UU_00011/5
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204979/Z/16/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18281/A20988
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_U127592696
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 201268/Z/16/Z
Pays : United Kingdom
Organisme : Department of Health
ID : RP-PG-0707-10034
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : CZD/16/6
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104036/Z/14/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/4
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18281/A19169
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
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