Dataset Information

Aberrant AHRR, ADAMTS2 and FAM184 DNA Methylation: Candidate Biomarkers in the Oral Rinse of Heavy Smokers.

ABSTRACT:

Objective

To identify DNA methylation patterns of heavy smokers in oral rinse samples.

Methods

Genome-wide DNA methylation data was imported from Gene Expression Omnibus GSE70977 using the GEOquery package. Two independent sets were analyzed: (a) 71 epigenomes of cancer-free subjects (heavy smokers n = 37 vs. non-smokers n = 31); for concordance assessment (b) 139 oral-cancer patients' epigenomes (heavy smokers n = 92 vs. non-smokers n = 47). Differential DNA methylation for CpG positions and at the regional level was determined using Limma and DMRcate Bioconductor packages. The linear model included sex, age, and alcohol consumption. The statistical threshold was set to p < 0.05. Functional gene prioritization analysis was performed for gene-targeted analysis.

Results

In individuals without cancer and heavy smokers, the FAM184B gene was found with two CpG positions differentially hypermethylated (p = 0.012 after FDR adjustment), in a region of 48 bp with an absolute methylation difference >10% between groups (p = 1.76 × 10^-8). In the analysis corresponding to oral-cancer patients, we found AHRR differentially hypomethylated cancer patients, but also in subjects without oral cancer in the targeted analyses. Remarkably, ADAMTS2 was found differentially hypermethylated in heavy smokers without a diagnosis of cancer in two consecutive probes cg05575921 (p = 3.13 × 10^-7) and cg10208897 (p = 1.36 × 10^-5).

Conclusions

Differentially methylated AHRR, ADAMTS2, and FAM184B genes are biomarker candidates in oral rinse samples.

SUBMITTER: Hernandez HG

PROVIDER: S-EPMC10376800 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Aberrant <i>AHRR</i>, <i>ADAMTS2</i> and <i>FAM184</i> DNA Methylation: Candidate Biomarkers in the Oral Rinse of Heavy Smokers.

Hernández Hernán Guillermo HG Aranzazu-Moya Gloria Cristina GC Pinzón-Reyes Efraín Hernando EH

Biomedicines 20230623 7

<h4>Objective</h4>To identify DNA methylation patterns of heavy smokers in oral rinse samples.<h4>Methods</h4>Genome-wide DNA methylation data was imported from Gene Expression Omnibus <i>GSE70977</i> using the GEOquery package. Two independent sets were analyzed: (a) 71 epigenomes of cancer-free subjects (heavy smokers <i>n</i> = 37 vs. non-smokers <i>n</i> = 31); for concordance assessment (b) 139 oral-cancer patients' epigenomes (heavy smokers <i>n</i> = 92 vs. non-smokers <i>n</i> = 47). Dif ...[more]

PMID: 37509437

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Project description:BackgroundA low level of methylation at cg05575921 in the aryl-hydrocarbon receptor repressor (AHRR) gene is robustly associated with smoking, and some studies have observed associations between cg05575921 methylation and increased lung cancer risk and mortality. To prospectively examine whether decreased methylation at cg05575921 may identify high risk subpopulations for lung cancer screening among heavy smokers, and mortality in cases, we evaluated associations between cg05575921 methylation and lung cancer risk and mortality, by histotype, in heavy smokers.MethodsThe β-Carotene and Retinol Efficacy Trial (CARET) included enrollees ages 45-69 with ≥ 20 pack-year smoking histories and/or occupational asbestos exposure. A subset of CARET participants had cg05575921 methylation available from HumanMethylationEPIC assays of blood collected on average 4.3 years prior to lung cancer diagnosis in cases. Cg05575921 methylation β-values were treated continuously for a 10% methylation decrease and as quintiles, where quintile 1 (Q1, referent) represents high methylation and Q5, low methylation. We used conditional logistic regression models to examine lung cancer risk overall and by histotype in a nested case-control study including 316 lung cancer cases (diagnosed through 2005) and 316 lung cancer-free controls matched on age (±5 years), sex, race/ethnicity, enrollment year, current/former smoking, asbestos exposure, and follow-up time. Mortality analyses included 372 lung cancer cases diagnosed between 1985 and 2013 with available methylation data. We used Cox proportional hazards models to examine mortality overall and by histotype.ResultsDecreased cg05575921 methylation was strongly associated with smoking, even in our population of heavy smokers. We did not observe associations between decreased pre-diagnosis cg05575921 methylation and increased lung cancer risk, overall or by histotype. We observed linear increasing trends for lung cancer-specific mortality across decreasing cg05575921 methylation quintiles for adenocarcinoma and small cell carcinoma (P-trends = 0.01 and 0.04, respectively).ConclusionsIn our study of heavy smokers, decreased cg05575921 methylation was strongly associated with smoking but not increased lung cancer risk. The observed association between cg05575921 methylation and increased mortality in adenocarcinoma and small cell histotypes requires further examination. Our results do not support using decreased cg05575921 methylation as a biomarker for lung cancer screening risk stratification.