Evidence map›Paper›PMID 25368192›Full record

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.

James M Amos-Landgraf, Jarom Heijmans, Mattheus C B Wielenga, Elisa Dunkin, Kathy J Krentz, Linda Clipson, Antwan G Ederveen, Patrick G Groothuis, Sietse Mosselman, Vanesa Muncan and 4 more

Abstract readComparative Study
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.

  1. 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 · 2022
    Pooled it
  2. Article
  3. Pathophysiology of colitis-associated colorectal cancer.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  4. Review
  5. 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 · 2026
    Article
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21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

James M Amos-LandgrafMcArdle Laboratory for Cancer Research, Department of Oncology and Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706; amoslandgrafj@missouri.edu dove@oncology.wisc.edu.
Jarom HeijmansTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands;
Mattheus C B WielengaTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands;
Elisa DunkinMcArdle Laboratory for Cancer Research, Department of Oncology and.
Kathy J KrentzMcArdle Laboratory for Cancer Research, Department of Oncology and.
Linda ClipsonMcArdle Laboratory for Cancer Research, Department of Oncology and.
Antwan G EderveenWomen's Health Department, Merck, Sharpe and Dohme, 5342 CC, Oss, The Netherlands; and.
Patrick G GroothuisWomen's Health Department, Merck, Sharpe and Dohme, 5342 CC, Oss, The Netherlands; and.
Sietse MosselmanWomen's Health Department, Merck, Sharpe and Dohme, 5342 CC, Oss, The Netherlands; and.
Vanesa MuncanTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands;
Daniel W HommesCenter for Inflammatory Bowel Diseases, University of California, Los Angeles, CA 90095.
Alexandra ShedlovskyMcArdle Laboratory for Cancer Research, Department of Oncology and.
William F DoveMcArdle Laboratory for Cancer Research, Department of Oncology and Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706; amoslandgrafj@missouri.edu dove@oncology.wisc.edu.
Gijs R van den BrinkTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands;
Center for Cancer Research · USAcademic Medical Center · NLMerck (Netherlands) · NLUniversity of California, Los Angeles · US

Funding

CELL CYCLE, DEVELOPMENT, AND NEOPLASIAR01CA063677 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI DOVE, WILLIAM FRANKLIN · 1993 to 2012
$1.4M
The Pirc Rat, a Newly Generated Model for Familial Human Colon CancerR01CA125591 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI DOVE, WILLIAM FRANKLIN · 2007 to 2011
$1.4M
NCI NIH HHS R01 CA063677NCI NIH HHS R01 CA125591NCI NIH HHS R01 CA63677
6 · The paper itself

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.

Indexed as

AdenomaAdenomatous Polyposis ColiAnimalsAnimals, CongenicAzoxymethaneCarcinogensColonic NeoplasmsDihydrotestosteroneDisease Models, AnimalEstradiolFemaleGenes, APCGonadal Steroid HormonesHormone Replacement TherapyHumansMaleAzoxymethaneCarcinogensDihydrotestosteroneEstradiolGonadal Steroid HormonesMedroxyprogesterone AcetateReceptors, AndrogenRNA, Messengerandrogensanimal modelscolon cancerestrogensintestinal regionality

Identifiers

PMID25368192
PMCPMC4246303
OpenAlexW2133067077

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.