ArticleProceedings of the National Academy of Sciences of the United States of America2012
Aristolochic acid-associated urothelial cancer in Taiwan.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers, 2 of them syntheses that pooled it.
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Who cites it
184 citing papers in PubMed, 2 syntheses or guidelines pooled it, 411 citations in OpenAlex.
- Aristolochic acid-containing Chinese herbal medicine and upper urinary tract urothelial carcinoma in Taiwan: a narrative review.World journal of urology · 2023Pooled it
- Risk assessment of upper tract urothelial carcinoma related to aristolochic acid.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2013Pooled it
- Toripalimab in patients with previously treated advanced upper tract urothelial carcinoma: a subgroup analysis of the phase II POLARIS-03 trial.The oncologist · 2026Trial
- Tislelizumab combined with gemcitabine as first-line treatment in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma: a single center, single-arm phase 2 trial.Frontiers in immunology · 2026Trial
- Aristolochic Acid and Alternative Lengthening of Telomeres Mechanisms Underlie Liver Angiosarcoma Pathogenesis.Liver cancer · 2026Article
- Beyond Tradition: An Integrated Toxicological, Ecological, and Public Health Perspective on Aristolochic Acids.Journal of applied toxicology : JAT · 2026Review
- Environmental exposures and multiple myeloma risk: A contemporary review of epidemiologic associations and mechanistic plausibility.Blood reviews · 2026Review
- Associations between PM2.5 exposure and upper tract urothelial carcinoma in a taiwanese case-control study.International urology and nephrology · 2026Article
- Performance of Urine Fluorescence In Situ Hybridization for Diagnosis of Upper Tract Urothelial Carcinoma: A Comprehensive Review.International journal of molecular sciences · 2026Review
- Sex-specific toxicity targets of aristolochic acids: nephrotoxicity in males, hepatotoxicity in females.Archives of toxicology · 2026Article
- Experimental models of chemical carcinogenesis: bridging toxicology and preclinical pharmacology.Journal of the Egyptian National Cancer Institute · 2026Review
- Post-transplant malignancies in Taiwanese kidney transplant recipients: incidence, temporal trends, and immunosuppressive risk factors in a two-decade single-center cohort.Frontiers in immunology · 2026Article
- Article
- Krüppel-Like Factor 6 Induces RNA Polymerase II Subunit RPB1 to Promote Kidney Injury.Journal of the American Society of Nephrology : JASN · 2025Article
- Whether aristolochic acid directly drives hepatocarcinogenesis: comprehensive investigations from mutational signatures to animal models.Archives of toxicology · 2025Review
- Transcription-Coupled Nucleotide Excision Repair: A Faster Solution or the Only Option?Biomolecules · 2025Review
- Synthesis and Cytotoxicity Evaluation of Denitroaristolochic Acids: Structural Insights and Mechanistic Implications in Nephrotoxicity.Biomolecules · 2025Article
- A perspective review on factors that influence mutagenicity in medicinal plants and their health implications.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- A novel mouse model of upper tract urothelial carcinoma highlights the impact of dietary intervention on gut microbiota and carcinogenesis prevention despite carcinogen exposure.International journal of cancer · 2025Article
- Repurposing of Metformin to Improve Survival Outcomes in Patients With Upper Tract Urothelial Carcinoma.Cancer medicine · 2025Article
124 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
Abstract
Aristolochic acid, a potent human carcinogen produced by Aristolochia plants, is associated with urothelial carcinoma of the upper urinary tract (UUC). Following metabolic activation, aristolochic acid reacts with DNA to form aristolactam (AL)-DNA adducts. These lesions concentrate in the renal cortex, where they serve as a sensitive and specific biomarker of exposure, and are found also in the urothelium, where they give rise to a unique mutational signature in the TP53 tumor-suppressor gene. Using AL-DNA adducts and TP53 mutation spectra as biomarkers, we conducted a molecular epidemiologic study of UUC in Taiwan, where the incidence of UUC is the highest reported anywhere in the world and where Aristolochia herbal remedies have been used extensively for many years. Our study involves 151 UUC patients, with 25 patients with renal cell carcinomas serving as a control group. The TP53 mutational signature in patients with UUC, dominated by otherwise rare A:T to T:A transversions, is identical to that observed in UUC associated with Balkan endemic nephropathy, an environmental disease. Prominent TP53 mutational hotspots include the adenine bases of (5')AG (acceptor) splice sites located almost exclusively on the nontranscribed strand. A:T to T:A mutations also were detected at activating positions in the FGFR3 and HRAS oncogenes. AL-DNA adducts were present in the renal cortex of 83% of patients with A:T to T:A mutations in TP53, FGFR3, or HRAS. We conclude that exposure to aristolochic acid contributes significantly to the incidence of UUC in Taiwan, a finding with significant implications for global public health.
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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 OpenQuestion graph.