Evidence map›Paper›PMID 30107003›Full record

Trial reportPloS one2018

The vitamin D receptor gene as a determinant of survival in pancreatic cancer patients: Genomic analysis and experimental validation.

Federico Innocenti, Kouros Owzar, Chen Jiang, Amy S Etheridge, Raluca Gordân, Alexander B Sibley, Flora Mulkey, Donna Niedzwiecki, Dylan Glubb, Nicole Neel and 14 more

Open access · goldAbstract readClinical Trial, Phase IIIRandomized Controlled TrialValidation Study
In one paragraph

Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 24% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
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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

24 authors at 9 institutions in 2 countries.

Federico InnocentiUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States of America.ORCID 0000-0001-9247-979X
Kouros OwzarDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, United States of America.
Chen JiangDuke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
Amy S EtheridgeUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States of America.
Raluca GordânDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, United States of America.
Alexander B SibleyDuke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
Flora MulkeyDuke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
Donna NiedzwieckiDuke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
Dylan GlubbUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States of America.
Nicole NeelUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States of America.
Mark S TalamontiNorth Shore University Health System, Evanston, IL, United States of America.
David J BentremNorthwestern University, Chicago, IL, United States of America.
Eric SeiserUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States of America.
Jen Jen YehUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States of America.
Katherine Van LoonUniversity of California at San Francisco, San Francisco, CA, United States of America.
Howard McLeodMoffitt Cancer Center, Tampa, FL, United States of America.
Mark J RatainUniversity of Chicago, Chicago, IL, United States of America.
Hedy L KindlerUniversity of Chicago, Chicago, IL, United States of America.
Alan P VenookUniversity of California at San Francisco, San Francisco, CA, United States of America.
Yusuke NakamuraUniversity of Chicago, Chicago, IL, United States of America.
Michiaki KuboCenter for Genomic Medicine, RIKEN, Yokohama, Japan.
Gloria M PetersenMayo Clinic, Rochester, MN, United States of America.
William R BamletMayo Clinic, Rochester, MN, United States of America.
Robert R McWilliamsMayo Clinic, Rochester, MN, United States of America.
University of North Carolina at Chapel Hill · USDuke Medical Center · USMayo Clinic in Florida · USUniversity of Chicago · USDuke University · USMoffitt Cancer Center · USNorthShore University HealthSystem · USNorthwestern University · USRIKEN Center for Integrative Medical Sciences · JP

Funding

Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis · 2014 to 2026
$177.3M
Statistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0M
CANCER &LEUKEMIA GROUP B STATISTICAL CENTERU10CA033601 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SARGENT, DANIEL J. · 1985 to 2013
$69.4M
Tissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI BILLADEAU, DANIEL D, PETERSEN, GLORIA M. · 2004 to 2018
$32.7M
Role of Vav1 protooncogene in pancreatic cancerP20CA102701 · NCI · MAYO CLINIC COLL OF MEDICINE, ROCHESTER · PI URRUTIA, RAUL A · 2003 to 2003
$1.5M
Genome-Wide molecular epidemiology of treatment outcome and cancer riskK07CA140390 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI INNOCENTI, FEDERICO · 2009 to 2013
$648k
Data commons for 'omic, microscopy and analysis core facilitiesS10OD018164 · OD · DUKE UNIVERSITY · PI WRAY, GREGORY A. · 2014 to 2014
$598k
NCI NIH HHS K07 CA140390NCI NIH HHS P20 CA102701NCI NIH HHS P50 CA102701NCI NIH HHS U10 CA033601NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180882NIH HHS S10 OD018164
6 · The paper itself

Abstract

purposeAdvanced pancreatic cancer is a highly refractory disease almost always associated with survival of little more than a year. New interventions based on novel targets are needed. We aim to identify new genetic determinants of overall survival (OS) in patients after treatment with gemcitabine using genome-wide screens of germline DNA. We aim also to support these findings with in vitro functional analysis. PATIENTS AND

methodsGenome-wide screens of germline DNA in two independent cohorts of pancreatic cancer patients (from the Cancer and Leukemia Group B (CALGB) 80303 and the Mayo Clinic) were used to select new genes associated with OS. The vitamin D receptor gene (VDR) was selected, and the interactions of genetic variation in VDR with circulating vitamin D levels and gemcitabine treatment were evaluated. Functional effects of common VDR variants were also evaluated in experimental assays in human cell lines.

resultsThe rs2853564 variant in VDR was associated with OS in patients from both the Mayo Clinic (HR 0.81, 95% CI 0.70-0.94, p = 0.0059) and CALGB 80303 (HR 0.74, 0.63-0.87, p = 0.0002). rs2853564 interacted with high pre-treatment levels of 25-hydroxyvitamin D (25(OH)D, a measure of endogenous vitamin D) (p = 0.0079 for interaction) and with gemcitabine treatment (p = 0.024 for interaction) to confer increased OS. rs2853564 increased transcriptional activity in luciferase assays and reduced the binding of the IRF4 transcription factor.

conclusionOur findings propose VDR as a novel determinant of survival in advanced pancreatic cancer patients. Common functional variation in this gene might interact with endogenous vitamin D and gemcitabine treatment to determine improved patient survival. These results support evidence for a modulatory role of the vitamin D pathway for the survival of advanced pancreatic cancer patients.

Indexed as

Genetic Predisposition to DiseaseAdenocarcinomaAgedAntimetabolites, AntineoplasticAntineoplastic Agents, ImmunologicalBevacizumabCell Line, TumorDeoxycytidineDouble-Blind MethodDrug Therapy, CombinationFemaleFollow-Up StudiesGemcitabineGenome-Wide Association StudyHumansMaleAntimetabolites, AntineoplasticAntineoplastic Agents, ImmunologicalBevacizumabDeoxycytidineGemcitabineReceptors, CalcitriolRNA, MessengerVDR protein, humanVitamin D

Identifiers

PMID30107003
PMCPMC6091939
OpenAlexW3037657163

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.