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

Overview of attention for article published in PLoS ONE, August 2018
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Title
The vitamin D receptor gene as a determinant of survival in pancreatic cancer patients: Genomic analysis and experimental validation
Published in
PLoS ONE, August 2018
DOI 10.1371/journal.pone.0202272
Pubmed ID
Authors

Federico Innocenti, Kouros Owzar, Chen Jiang, Amy S. Etheridge, Raluca Gordân, Alexander B. Sibley, Flora Mulkey, Donna Niedzwiecki, Dylan Glubb, Nicole Neel, Mark S. Talamonti, David J. Bentrem, Eric Seiser, Jen Jen Yeh, Katherine Van Loon, Howard McLeod, Mark J. Ratain, Hedy L. Kindler, Alan P. Venook, Yusuke Nakamura, Michiaki Kubo, Gloria M. Petersen, William R. Bamlet, Robert R. McWilliams

Abstract

Advanced 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. Genome-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. The 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. Our 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.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 7 41%
Student > Bachelor 3 18%
Student > Master 3 18%
Researcher 2 12%
Student > Ph. D. Student 2 12%
Other 0 0%
Readers by discipline Count As %
Unspecified 7 41%
Biochemistry, Genetics and Molecular Biology 3 18%
Medicine and Dentistry 2 12%
Agricultural and Biological Sciences 2 12%
Physics and Astronomy 1 6%
Other 2 12%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 November 2018.
All research outputs
#9,898,153
of 12,931,128 outputs
Outputs from PLoS ONE
#97,001
of 139,913 outputs
Outputs of similar age
#183,348
of 265,359 outputs
Outputs of similar age from PLoS ONE
#1,373
of 1,911 outputs
Altmetric has tracked 12,931,128 research outputs across all sources so far. This one is in the 20th percentile – i.e., 20% of other outputs scored the same or lower than it.
So far Altmetric has tracked 139,913 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.9. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
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We're also able to compare this research output to 1,911 others from the same source and published within six weeks on either side of this one. This one is in the 24th percentile – i.e., 24% of its contemporaries scored the same or lower than it.