Evidence map›Paper›PMID 40285850›Full record

ArticleArchives of toxicology2025

LINE-1 DNA methylation mediates smoking-related risk in site-specific urothelial carcinoma: a Taiwan case-control study.

Chien-Hung Lin, Peir-Haur Hung, Chao-Hsiang Chang, Han Chang, Mu-Chi Chung, Wen-Chi Chang, Chi-Jung Chung

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Article in Archives of toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Chien-Hung Lin *Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
Peir-Haur Hung *Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
Chao-Hsiang ChangDepartment of Urology, China Medical University and Hospital, Taichung, Taiwan.
Han ChangDepartment of Pathology, College of Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Mu-Chi ChungDivision of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Wen-Chi ChangDepartment of Public Health, College of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City, 406040, Taiwan.
Chi-Jung ChungDepartment of Public Health, College of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City, 406040, Taiwan. cjchung@mail.cmu.edu.tw.ORCID 0000-0003-0186-2692

Funding

China Medical University, Taiwan CMU112-MF-56China Medical University, Taiwan CMU113-SR-89China Medical University, Taiwan CMUH-HBB110-003China Medical University, Taiwan DMR-113-140Ditmanson Medical Foundation Chia-Yi Christian Hospital R113-10National Science Council MOST 108-2221-E-039-009-MY3National Science Council NSTC 112-2314-B-039-032
6 · The paper itself

Abstract

While environmental and lifestyle factors contribute to urothelial carcinoma (UC) development, their differential effects on bladder cancer (UB) versus upper tract urothelial carcinoma (UTUC) and the underlying epigenetic mechanisms remain unclear. This study investigated location-specific risk factors and the mediating role of LINE-1 DNA methylation in UC carcinogenesis. A hospital-based case-control study was conducted, comprising 478 UC cases (266 UB, 204 UTUC) and 569 controls. The risk factors, including smoking, Chinese herbal medicine use, comorbidities, and blood levels of arsenic, cadmium, and lead, were assessed through questionnaires and blood sample analysis. LINE-1 DNA methylation levels were measured by pyrosequencing. LASSO regression for variable selection and logistic regression for risk assessment. Mediation analysis was performed to evaluate the role of LINE-1 DNA methylation in the relationship between environmental exposures and UC risk. UB risk was associated with male sex, smoking, chronic kidney disease (CKD), elevated blood arsenic, and diabetes (all p < 0.0001), while UTUC risk was primarily linked to female sex (p = 0.0004) and CKD (p < 0.0001). LINE-1 hypermethylation was associated with both UB and UTUC risk (p < 0.0001). Notably, LINE-1 methylation significantly mediated the relationship between smoking and UC risk, particularly in males, while no significant mediation was observed for other exposures. This study demonstrates distinct risk profiles for UB and UTUC, and identifies LINE-1 methylation as a key mediator in smoking-related UC risk, especially in men. These findings suggest the need for location-specific prevention strategies and highlight the importance of epigenetic mechanisms in UC development.

Indexed as

DNA MethylationLong Interspersed Nucleotide ElementsSmokingUrinary Bladder NeoplasmsUrologic NeoplasmsAgedCase-Control StudiesEnvironmental ExposureEpigenesis, GeneticFemaleHumansMaleMiddle AgedRisk FactorsTaiwanArsenicBladder cancerCadmiumChinese herbsDNA methylationHeavy metalsLasso regressionLeadLINE-1MediationRandom forestSmokingUpper tract urothelial carcinomaUrothelial carcinomaVariable importance selection

Identifiers

PMID40285850
PMCPMC12198073

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.