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Record W1967765404 · doi:10.1371/journal.pone.0117574

Vitamin D Metabolic Pathway Genes and Pancreatic Cancer Risk

2015· article· en· W1967765404 on OpenAlexaff
Hannah Arem, Kai Yu, Xiaoqin Xiong, Kristin A. Moy, Neal D. Freedman, Susan T. Mayne, Demetrius Albanes, Alan A. Arslan, Melissa A. Austin, William R. Bamlet, Laura E. Beane Freeman, Paige M. Bracci, Federico Canzian, Michelle Cotterchio, Eric J. Duell, Steve Gallinger, Graham G. Giles, Michael Goggins, Phyllis J. Goodman, Patricia Hartge, Manal M. Hassan, Kathy J. Helzlsouer, Brian E. Henderson, Elizabeth A. Holly, Robert N. Hoover, Eric J. Jacobs, Aruna Kamineni, Alison P. Klein, Eric A. Klein, Laurence N. Kolonel, Donghui Li, Núria Malats, Satu Männistö, Marjorie L. McCullough, Sara H. Olson, Irene Orlow, Ulrike Peters, Gloria M. Petersen, Miquel Porta, Gianluca Severi, Xiao‐Ou Shu, Kala Visvanathan, Emily White, Herbert Yu, Anne Zeleniuch‐Jacquotte, Wei Zheng, Geoffrey S. Tobias, Dennis Maeder, Michelle Brotzman, Harvey A. Risch, Joshua N. Sampson, Rachael Z. Stolzenberg‐Solomon

Bibliographic record

VenuePLoS ONE · 2015
Typearticle
Languageen
FieldMedicine
TopicVitamin D Research Studies
Canadian institutionsLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalCancer Care OntarioUniversity of Toronto
FundersNational Cancer InstituteNational Institutes of Health
KeywordsCYP24A1Pancreatic cancerSingle-nucleotide polymorphismVitamin D and neurologyInternal medicineCalcitriol receptorBiologyEndocrinologyPopulationOncologyMedicineCancerGenotypeGeneticsGene

Abstract

fetched live from OpenAlex

Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186), LRP2 (rs4668123), CYP24A1 (rs2762932), GC (rs2282679), and CUBN (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.078
GPT teacher head0.300
Teacher spread0.222 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations34
Published2015
Admission routes1
Has abstractyes

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Same venuePLoS ONESame topicVitamin D Research StudiesFrench-language works237,207