Evidence map›Paper›PMID 24894197›Full record

Trial reportCancer prevention research (Philadelphia, Pa.)2014

A functional variant in NKX3.1 associated with prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Erin E Martinez, Amy K Darke, Catherine M Tangen, Phyllis J Goodman, Jay H Fowke, Eric A Klein, Sarki A Abdulkadir

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Cancer prevention research (Philadelphia, Pa.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04014283 (Prevention of Females Malignancies in Families With Hereditary Breast Cancer by Personalized Optimization of Se Levels in the Organism.), which is not on this map. Cited by 13 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 2 pooled it
2.6field-weighted citation impact, top 10% 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.

NCT04014283 naunknown statusnot on this map

Prevention of Females Malignancies in Families With Hereditary Breast Cancer by Personalized Optimization of Se Levels in the Organism.

TypeinterventionalSponsorRead-Gene S.A.Ran2014 to 2023Enrolled7,000ConditionsBreast NeoplasmsArmsSelenium supplementation or placebo treatment, Diet modification, Selenium supplementation or placebo treatment and diet modification
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Selenium for preventing cancer.The Cochrane database of systematic reviews · 2018
    Pooled it
  3. Trial
  4. Review
  5. Review
  6. Article
  7. Review
  8. Organoids Increase the Predictive Value ofFrontiers in oncology · 2019
    Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 2 countries.

Erin E MartinezDepartments of Pathology, Microbiology and Immunology.
Amy K DarkeSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington;
Catherine M TangenSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington;
Phyllis J GoodmanSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington;
Jay H FowkeSurgical Urology, Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
Eric A KleinCleveland Clinic Foundation, Cleveland, Ohio; and.
Sarki A AbdulkadirDepartments of Pathology, Microbiology and Immunology, Cancer Biology, and Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois sarki.abdulkadir@northwestern.edu.
Fred Hutch Cancer Center · USBipar · FRCleveland Clinic · USNorthwestern University · USVanderbilt University · US

Funding

SWOG Foreign AccrualsU10CA037429 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BLANKE, CHARLES D., MEYSKENS, FRANK L. · 1985 to 2014
$205.2M
SWOG - Foreign Accrual under UMiU10CA032102 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BLANKE, CHARLES D. · 1985 to 2013
$141.3M
SWOG NCORP Research BaseUG1CA189974 · NCI · THE HOPE FOUNDATION · PI CHARLES D. BLANKE, DAWN HERSHMAN · 2014 to 2026
$80.6M
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
PCPT and SELECT cohorts: Core Infrastructure Support for Cancer Research UM1CA182883 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TANGEN, CATHERINE M., THOMPSON, IAN M. · 2013 to 2017
$5.2M
Role of Oncogenic Kinase Pim-1 in Prostate CancerR01CA123484 · NCI · VANDERBILT UNIVERSITY · PI ABDULKADIR, SARKI A. · 2007 to 2017
$2.9M
Genetic and Endocrine Pathways Linking Obesity with Prostate CancerR01CA121060 · NCI · VANDERBILT UNIVERSITY · PI FOWKE, JAY H. · 2007 to 2011
$2.8M
Modeling Prostate TumorigenesisR01CA094858 · NCI · VANDERBILT UNIVERSITY · PI ABDULKADIR, SARKI A. · 2002 to 2012
$2.5M
NCATS NIH HHS 2 UL1 TR000445-06NCATS NIH HHS UL1 TR000445NCI NIH HHS CA37429NCI NIH HHS R01 CA094858NCI NIH HHS R01 CA121060NCI NIH HHS R01CA121060NCI NIH HHS R01 CA123484NCI NIH HHS R01CA94858NCI NIH HHS U10 CA032102NCI NIH HHS U10 CA037429NCI NIH HHS U10 CA32102NCI NIH HHS UG1 CA189974NCI NIH HHS UM1 CA182883NCRR NIH HHS UL1 RR024975NCRR NIH HHS UL1 RR024975-01
6 · The paper itself

Abstract

NKX3.1 is an androgen-regulated prostate tumor suppressor protein. We previously found that antioxidant administration (N-acetylcysteine) in the Nkx3.1 knockout mouse model promoted prostate epithelial proliferation, suggesting that NKX3.1 activity modifies the effect of antioxidant administration on prostate carcinogenesis. Interestingly, administration of the antioxidant vitamin E significantly increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), suggesting that our animal experiments may be relevant to humans. To determine whether NKX3.1 played a role in increased human prostate cancer risk associated with antioxidant administration in SELECT, we investigated the joint risk of antioxidant administration and NKX3.1 genotypes previously found to be associated with decreased NKX3.1 mRNA expression (rs11781886) or DNA-binding activity in vitro (rs2228013) in the SELECT biomarker case-cohort substudy (1,866 cases; 3,135 non-cases). Multivariable COX regression models were developed to determine the joint association of NKX3.1 genotypes with administration of vitamin E, selenium, or the combination, compared with placebo. The CC genotype at rs11781886 combined with selenium administration was associated with increased overall prostate cancer risk [HR, 1.676; 95% confidence interval (CI), 1.011-2.777; P = 0.045] and low-grade prostate cancer risk (HR, 1.811; 95% CI, 1.016-3.228; P = 0.0441). Similarly, the rs11781886 minor allele (CC+CT) combined with vitamin E administration was significantly associated with increased prostate cancer risk (HR, 1.450; 95% CI, 1.117-1.882; P = 0.0052). Our results indicate that variation in NKX3.1 expression combined with selenium or vitamin E treatment modifies the risk of prostate cancer. Genetic background may modulate the effects of antioxidant supplementation thought to act as chemoprevention agents.

Indexed as

AgedAntioxidantsCase-Control StudiesGenotypeHomeodomain ProteinsHumansMaleMiddle AgedPolymorphism, Single NucleotideProportional Hazards ModelsProstatic NeoplasmsRisk FactorsTranscription FactorsVitamin EVitaminsAntioxidantsHomeodomain ProteinsNKX3-1 protein, humanTranscription FactorsVitamin EVitamins

Identifiers

PMID24894197
PMCPMC4154984
OpenAlexW2125517720

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

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.