Evidence map›Paper›PMID 34059701›Full record

ArticleScientific reports2021

Prostate cancer risk variants of the HOXB genetic locus.

William D Dupont, Joan P Breyer, Spenser H Johnson, W Dale Plummer, Jeffrey R Smith

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Scalable and accurate rare-variant association tests for whole genome sequencing time-to-event analysis in large biobanks.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Prostate cancer in omics era.Cancer cell international · 2022
    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

5 authors at 2 institutions in 1 country.

William D DupontDepartment of Biostatistics, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Joan P BreyerDepartment of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Spenser H JohnsonDepartment of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
W Dale PlummerDepartment of Biostatistics, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Jeffrey R SmithDepartment of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA. jeffrey.smith@vumc.org.
Vanderbilt University Medical Center · USVA Tennessee Valley Healthcare System · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Heritable Risk Factors for Familial Prostate CancerI01BX002502 · VA · VETERANS HEALTH ADMINISTRATION · PI SMITH, JEFFREY R. · 2014 to 2017
–
The Genetic Origin of Hereditary Prostate CancerI01CX002155 · VA · VETERANS HEALTH ADMINISTRATION · PI SMITH, JEFFREY R. · 2021 to 2025
–
BLRD VA I01 BX002502CSRD VA I01 CX002155NCATS NIH HHS UL1 TR000445NCI NIH HHS P30 CA068485NIH HHS UL1 TR000445
6 · The paper itself

Abstract

The G84E germline mutation of HOXB13 predisposes to prostate cancer and is clinically tested for familial cancer care. We investigated the HOXB locus to define a potentially broader contribution to prostate cancer heritability. We sought HOXB locus germline variants altering prostate cancer risk in three European-ancestry case-control study populations (combined 7812 cases and 5047 controls): the International Consortium for Prostate Cancer Genetics Study; the Nashville Familial Prostate Cancer Study; and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Multiple rare genetic variants had concordant and strong risk effects in these study populations and exceeded genome-wide significance. Independent risk signals were best detected by sentinel variants rs559612720 within SKAP1 (OR = 8.1, P = 2E-9) and rs138213197 (G84E) within HOXB13 (OR = 5.6, P = 2E-11), separated by 567 kb. Half of carriers inherited both risk alleles, while others inherited either alone. Under mutual adjustment, the variants separately carried 3.6- and 3.1-fold risk, respectively, while joint inheritance carried 11.3-fold risk. These risks were further accentuated among men meeting criteria for hereditary prostate cancer, and further still for those with early-onset or aggressive disease. Among hereditary prostate cancer cases diagnosed under age 60 and with aggressive disease, joint inheritance carried a risk of OR = 27.7 relative to controls, P = 2E-8. The HOXB sentinel variant pair more fully captured genetic risk for prostate cancer within the study populations than either variant alone.

Indexed as

Genetic Predisposition to DiseaseCase-Control StudiesGenotypeHomeodomain ProteinsHumansMaleMiddle AgedProstatic NeoplasmsHomeodomain ProteinsHOXB13 protein, human

Identifiers

PMID34059701
PMCPMC8167119
OpenAlexW3164128552

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.