ArticleBMC cancer2020
From tobacco smoking to cancer mutational signature: a mediation analysis strategy to explore the role of epigenetic changes.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- A timeless chronicle: Effects of cigarette smoke on GPR15 receptor and its oncogenic potential.Cancer letters · 2026Review
- BASCULE: bayesian inference and clustering of mutational signatures leveraging biological priors.Genome biology · 2025Article
- Tobacco Smoking Rewires Cell Metabolism by Inducing GAPDH Succinylation to Promote Lung Cancer Progression.Cancer research · 2025Article
- Methylation-based smoking signatures in blood and tissue samples for the prediction of self-reported smoking status and mortality in patients with colorectal cancer.Clinical epigenetics · 2025Article
- Artificial intelligence-based epigenomic, transcriptomic and histologic signatures of tobacco use in oral squamous cell carcinoma.NPJ precision oncology · 2024Article
- Methods for large-scale single mediator hypothesis testing: Possible choices and comparisons.Genetic epidemiology · 2023Review
- Signatures of malignant cells and novel therapeutic targets revealed by single-cell sequencing in lung adenocarcinoma.Cancer medicine · 2022Article
- Quantifying smoking exposure, genomic correlates, and related risk of treatment failure in p16+ squamous cell carcinoma of the oropharynx.Laryngoscope investigative otolaryngology · 2021Article
- Temporal trend of gastric cancer burden along with its risk factors in China from 1990 to 2019, and projections until 2030: comparison with Japan, South Korea, and Mongolia.Biomarker research · 2021Article
- The mutational landscape of early- and typical-onset oral tongue squamous cell carcinoma.Cancer · 2021Article
- Smoking, DNA Methylation, and Breast Cancer: A Mendelian Randomization Study.Frontiers in oncology · 2021Article
- Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundTobacco smoking is associated with a unique mutational signature in the human cancer genome. It is unclear whether tobacco smoking-altered DNA methylations and gene expressions affect smoking-related mutational signature.
methodsWe systematically analyzed the smoking-related DNA methylation sites reported from five previous casecontrol studies in peripheral blood cells to identify possible target genes. Using the mediation analysis approach, we evaluated whether the association of tobacco smoking with mutational signature is mediated through altered DNA methylation and expression of these target genes in lung adenocarcinoma tumor tissues.
resultsBased on data obtained from 21,108 blood samples, we identified 374 smoking-related DNA methylation sites, annotated to 248 target genes. Using data from DNA methylations, gene expressions and smoking-related mutational signature generated from ~ 7700 tumor tissue samples across 26 cancer types from The Cancer Genome Atlas (TCGA), we found 11 of the 248 target genes whose expressions were associated with smoking-related mutational signature at a Bonferroni-correction P < 0.001. This included four for head and neck cancer, and seven for lung adenocarcinoma. In lung adenocarcinoma, our results showed that smoking increased the expression of three genes, AHRR, GPR15, and HDGF, and decreased the expression of two genes, CAPN8, and RPS6KA1, which were consequently associated with increased smoking-related mutational signature. Additional evidence showed that the elevated expression of AHRR and GPR15 were associated with smoking-altered hypomethylations at cg14817490 and cg19859270, respectively, in lung adenocarcinoma tumor tissues. Lastly, we showed that decreased expression of RPS6KA1, were associated with poor survival of lung cancer patients.
conclusionsOur findings provide novel insight into the contributions of tobacco smoking to carcinogenesis through the underlying mechanisms of the elevated mutational signature by altered DNA methylations and gene expressions.
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