ArticleProceedings of the National Academy of Sciences of the United States of America2018
Genetic and epigenetic alterations in normal tissues have differential impacts on cancer risk among tissues.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Gastric Intestinal Metaplasia After Helicobacter pylori Eradication: Reframing the Reversibility Controversy.Digestive diseases and sciences · 2026Review
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- Early detection of gastric cancer via multiplex blood assay targeting CfDNA methylation signatures.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Unravelling the genetics and epigenetics of the ageing tumour microenvironment in cancer.Nature reviews. Cancer · 2025Review
- Article
- The methylation signature of hepatocellular carcinoma trajectory based on pseudotime and chronological time for predicting precancerous patients.The oncologist · 2025Article
- Clonal Hematopoiesis and Solid Cancers.Cancer science · 2025Review
- How chronic inflammation fuels carcinogenesis as an environmental epimutagen.Discover oncology · 2025Review
- Comparison of Genetic Mutations of Gastric Cancer Diagnosed before or after Helicobacter pylori Eradication and between Differentiated and Undifferentiated Types Using Next-Generation Sequencing.Digestive diseases (Basel, Switzerland) · 2025Article
- Early-onset cancers: Biological bases and clinical implications.Cell reports. Medicine · 2024Review
- The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.International journal of molecular sciences · 2024Review
- MIR124-3 and NKX6-1 hypermethylation profiles accurately predict metachronous gastric lesions in a Caucasian population.Clinical epigenetics · 2024Article
- YTHDF1 mediates N-methyl-N-nitrosourea-induced gastric carcinogenesis by controlling HSPH1 translation.Cell proliferation · 2024Article
- Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets.Signal transduction and targeted therapy · 2024Review
- Severe induction of aberrant DNA methylation by nodular gastritis in adults.Journal of gastroenterology · 2024Article
- Statistical Models for High-Risk Intestinal Metaplasia with DNA Methylation Profiling.Epigenomes · 2024Article
- On epigenetic stochasticity, entropy and cancer risk.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Chromosomal copy number amplification-driven Linc01711 contributes to gastric cancer progression through histone modification-mediated reprogramming of cholesterol metabolism.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence.Acta pharmaceutica Sinica. B · 2024Article
- Review
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17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic and epigenetic alterations are both involved in carcinogenesis, and their low-level accumulation in normal tissues constitutes cancer risk. However, their relative importance has never been examined, as measurement of low-level mutations has been difficult. Here, we measured low-level accumulations of genetic and epigenetic alterations in normal tissues with low, intermediate, and high cancer risk and analyzed their relative effects on cancer risk in the esophagus and stomach. Accumulation of genetic alterations, estimated as a frequency of rare base substitution mutations, significantly increased according to cancer risk in esophageal mucosae, but not in gastric mucosae. The mutation patterns reflected the exposure to lifestyle risk factors. In contrast, the accumulation of epigenetic alterations, measured as DNA methylation levels of marker genes, significantly increased according to cancer risk in both tissues. Patients with cancer (high-risk individuals) were precisely discriminated from healthy individuals with exposure to risk factors (intermediate-risk individuals) by a combination of alterations in the esophagus (odds ratio, 18.2; 95% confidence interval, 3.69-89.9) and by only epigenetic alterations in the stomach (odds ratio, 7.67; 95% confidence interval, 2.52-23.3). The relative importance of epigenetic alterations upon genetic alterations was 1.04 in the esophagus and 2.31 in the stomach. The differential impacts among tissues will be critically important for effective cancer prevention and precision cancer risk diagnosis.
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