ArticleProceedings of the National Academy of Sciences of the United States of America2003
Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
70 citing papers in PubMed, 195 citations in OpenAlex.
- Dietary polyamine intake and risk of colorectal adenomatous polyps.The American journal of clinical nutrition · 2012Trial
- Risk modification of colorectal adenoma by CYP7A1 polymorphisms and the role of bile acid metabolism in carcinogenesis.Cancer prevention research (Philadelphia, Pa.) · 2012Trial
- Variants downstream of the ornithine decarboxylase gene influence risk of colorectal adenoma and aspirin chemoprevention.Cancer prevention research (Philadelphia, Pa.) · 2011Trial
- Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and sulindac, and outcomes among colorectal adenoma patients.Journal of the National Cancer Institute · 2010Trial
- The effect of difluoromethylornithine on decreasing prostate size and polyamines in men: results of a year-long phase IIb randomized placebo-controlled chemoprevention trial.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2008Trial
- Polyamine Metabolism and the DHPS/eIF5A Hypusination Axis: From Metabolic Reprogramming to a Therapeutic Achilles' Heel in Melanoma.Biomolecules · 2026Review
- Navigating the Terrain of Post-Polypectomy Surveillance: Charting the Complex Landscape of Guidelines and Recurrence Risks.Canadian journal of gastroenterology & hepatology · 2026Review
- Plasma protein levels and hepatocellular carcinoma: a Mendelian randomization study with drug screening implications.Discover oncology · 2025Article
- Epidemiology and clinical characteristics of colorectal cancer and advanced adenoma: a single center experience in Jordan.BMC gastroenterology · 2025Article
- Phase 1 study of high-dose DFMO, celecoxib, cyclophosphamide and topotecan for patients with relapsed neuroblastoma: a New Approaches to Neuroblastoma Therapy trial.British journal of cancer · 2024Article
- Indomethacin Induces Spermidine/Spermine-NBiomolecules · 2023Article
- c-MYC-Driven Polyamine Metabolism in Ovarian Cancer: From Pathogenesis to Early Detection and Therapy.Cancers · 2023Review
- Polyamines and Their Metabolism: From the Maintenance of Physiological Homeostasis to the Mediation of Disease.Medical sciences (Basel, Switzerland) · 2022Review
- Article
- Genetic regulation of spermine oxidase activity and cancer risk: a Mendelian randomization study.Scientific reports · 2021Article
- A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma.Cancers · 2021Article
- Emerging Role ofGenes · 2021Article
- Do Aspirin and Flavonoids Prevent Cancer through a Common Mechanism Involving Hydroxybenzoic Acids?-The Metabolite Hypothesis.Molecules (Basel, Switzerland) · 2020Review
- Calcium Permeable Channels in Cancer Hallmarks.Frontiers in pharmacology · 2020Review
- Elucidating the Reprograming of Colorectal Cancer Metabolism Using Genome-Scale Metabolic Modeling.Frontiers in oncology · 2019Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Most sporadic colon adenomas acquire mutations in the adenomatous polyposis coli gene (APC) and show defects in APC-dependent signaling. APC influences the expression of several genes, including the c-myc oncogene and its antagonist Mad1. Ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, is a transcriptional target of c-myc and a modifier of APC-dependent tumorigenesis. A single-nucleotide polymorphism exists in intron 1 of the human ODC gene, which lies between two myc-binding domains. This region is known to affect ODC transcription, but no data exist on the relationship of this polymorphism to risk of colorectal neoplasia in humans. We show that individuals homozygous for the minor ODC A-allele who reported using aspirin are approximately 0.10 times as likely to have an adenoma recurrence as non-aspirin users homozygous for the major G-allele. Mad1 selectively suppressed the activity of the ODC promoter containing the A-allele, but not the G-allele, in a human colon cancer-derived cell line (HT29). Aspirin (>or=10 microM) did not affect ODC allele-specific promoter activity but did activate polyamine catabolism and lower polyamine content in HT29 cells. We propose that the ODC polymorphism and aspirin act independently to reduce the risk of adenoma recurrence by suppressing synthesis and activating catabolism, respectively, of colonic mucosal polyamines. These findings confirm the hypothesis that the ODC polymorphism is a genetic marker for colon cancer risk, and support the use of ODC inhibitors and aspirin, or other nonsteroidal antiinflammatory drugs (NSAIDs), in combination as a strategy for colon cancer prevention.
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Registered trials
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.