ArticleProceedings of the National Academy of Sciences of the United States of America2014
Sex disparity in colonic adenomagenesis involves promotion by male hormones, not protection by female hormones.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Circulating Sex Hormone Levels and Colon Cancer Risk in Men: A Nested Case-Control Study and Meta-Analysis.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Pooled it
- Secondary bile acid production by gut bacteria promotes Western diet-associated colorectal cancer.Gut · 2026Article
- Pathophysiology of colitis-associated colorectal cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Exploring Risk Factors and Sex Differences in Colorectal Cancer: Insights from Current Evidence.Cells · 2026Review
- Sex Differences in Colorectal Tumor-Associated T-cell Responses.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Combination of a pesco vegetarian diet with non-steroidal anti-inflammatory drugs reduces colorectal cancer risk and modulates gut microbiota in PIRC rats.Scientific reports · 2026Article
- Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications.Biology of sex differences · 2026Review
- Sex steroid receptors in colorectal cancer: implications for tumor progression, therapeutic opportunities, and sex-specific outcomes.Annals of medicine and surgery (2012) · 2026Review
- Targeting androgen receptor signaling to enhance cancer immunotherapy.Trends in pharmacological sciences · 2025Review
- Sexual dimorphism in colon is mediated by an androgen-IL33Cell & bioscience · 2025Article
- The Roles of Ninjurin1 and Estrogen in Modulating Azoxymethane/Dextran Sodium Sulfate-Induced Colitis-Associated Colorectal Cancer in Male Mice.Cancer research and treatment · 2025Article
- Evolving tumor microenvironment: Driving cancer initiation and progression in cardiovascular diseases.iScience · 2025Review
- Sustained Accumulation of Molecular Clock Suppressors Period 1 and Period 2 Promotes C2C12 Myotube Atrophy Through an Autocrine-Mediated Mechanism With Relevance to Androgen Deprivation-Induced Limb Muscle Mass Loss.Function (Oxford, England) · 2025Article
- Molecular signatures of xenograft colorectal cancer in mice treated with topotecan: A mass spectrometry-based study.Toxicology reports · 2025Article
- Ninjurin1 deficiency differentially mitigates colorectal cancer induced by azoxymethane and dextran sulfate sodium in male and female mice.International journal of cancer · 2025Article
- Testosterone and colorectal cancer: a bidirectional Mendelian randomization study.Translational cancer research · 2025Article
- Article
- A decade-long study on pathological distinctions of resectable early versus late onset colorectal cancer and optimal screening age determination.Scientific reports · 2024Article
- Sexual dimorphism in colorectal cancer: molecular mechanisms and treatment strategies.Biology of sex differences · 2024Review
- Sex differences in colorectal cancer: with a focus on sex hormone-gut microbiome axis.Cell communication and signaling : CCS · 2024Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
It recently has been recognized that men develop colonic adenomas and carcinomas at an earlier age and at a higher rate than women. In the Apc(Pirc/+) (Pirc) rat model of early colonic cancer, this sex susceptibility was recapitulated, with male Pirc rats developing twice as many adenomas as females. Analysis of large datasets revealed that the Apc(Min/+) mouse also shows enhanced male susceptibility to adenomagenesis, but only in the colon. In addition, WT mice treated with injections of the carcinogen azoxymethane (AOM) showed increased numbers of colonic adenomas in males. The mechanism underlying these observations was investigated by manipulation of hormonal status. The preponderance of colonic adenomas in the Pirc rat model allowed a statistically significant investigation in vivo of the mechanism of sex hormone action on the development of colonic adenomas. Females depleted of endogenous hormones by ovariectomy did not exhibit a change in prevalence of adenomas, nor was any effect observed with replacement of one or a combination of female hormones. In contrast, depletion of male hormones by orchidectomy (castration) markedly protected the Pirc rat from adenoma development, whereas supplementation with testosterone reversed that effect. These observations were recapitulated in the AOM mouse model. Androgen receptor was undetectable in the colon or adenomas, making it likely that testosterone acts indirectly on the tumor lineage. Our findings suggest that indirect tumor-promoting effects of testosterone likely explain the disparity between the sexes in the development of colonic adenomas.
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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.