MétaCan
Menu
Back to cohort
Record W2937929023 · doi:10.1002/cam4.1996

Evaluation of vitamin D biosynthesis and pathway target genes reveals <i>UGT2A1/2</i> and <i>EGFR</i> polymorphisms associated with epithelial ovarian cancer in African American Women

2019· article· en· W2937929023 on OpenAlexafffund
Delores J. Grant, Ani Manichaikul, Anthony J. Alberg, Elisa V. Bandera, Jill S. Barnholtz‐Sloan, Melissa L. Bondy, Michele L. Coté, Ellen Funkhouser, Patricia G. Moorman, Lauren C. Peres, Edward Peters, Ann G. Schwartz, Paul Terry, Xin‐Qun Wang, Temitope O. Keku, Cathrine Hoyo, Andrew Berchuck, Dale P. Sandler, Jack A. Taylor, Katie M. O’Brien, Digna R. Velez Edwards, Todd L. Edwards, Alicia Beeghly‐Fadiel, Nicolas Wentzensen, Celeste Leigh Pearce, Anna H. Wu, Alice S. Whittemore, Valerie McGuire, Weiva Sieh, Joseph H. Rothstein, Francesmary Modugno, Roberta B. Ness, Kirsten B. Moysich, Mary Anne Rossing, Jennifer A. Doherty, Thomas A. Sellers, Jennifer B. Permuth, Álvaro N.A. Monteiro, Douglas A. Levine, Veronica Wendy Setiawan, Christopher A. Haiman, Loı̈c Le Marchand, Lynne R. Wilkens, Beth Y. Karlan, Usha Menon, Susan J. Ramus, Simon A. Gayther, Aleksandra Gentry‐Maharaj, Kathryn L. Terry, Daniel W. Cramer, Ellen L. Goode, Melissa C. Larson, Scott H. Kaufmann, Rikki Cannioto, Kunle Odunsi, John Lewis Etter, Ruea‐Yea Huang, Marcus Q. Bernardini, Alicia Tone, Taymaa May, Marc T. Goodman, Pamela J. Thompson, Michael E. Carney, Shelley S. Tworoger, Elizabeth M. Poole, Diether Lambrechts, Ignace Vergote, Adriaan Vanderstichele, Els Van Nieuwenhuysen, Hoda Anton‐Culver, Argyrios Ziogas, James D. Brenton, Line Bjørge, Helga B. Salvensen, Lambertus A. Kiemeney, Leon F.A.G. Massuger, Tanja Pejović, Amanda Bruegl, Melissa Moffitt, Linda S. Cook, Nhu D. Le, Angela Brooks‐Wilson, Linda E. Kelemen, Paul D.P. Pharoah, Honglin Song, Ian Campbell, Diana Eccles, Anna DeFazio, Catherine J. Kennedy, Joellen M. Schildkraut

Bibliographic record

VenueCancer Medicine · 2019
Typearticle
Languageen
FieldMedicine
TopicOvarian cancer diagnosis and treatment
Canadian institutionsSimon Fraser UniversityBC Cancer AgencyCanada's Michael Smith Genome Sciences CentrePrincess Margaret Cancer CentreUniversity Health Network
FundersNational Institute of Environmental Health SciencesNational Cancer InstituteNIHR Cambridge Biomedical Research CentreNational Health and Medical Research CouncilNational Center for Advancing Translational SciencesMedical Research CouncilUniversity of North Carolina at Chapel HillNational Institutes of HealthNorges ForskningsrådHelse VestMinisterio de Economía y CompetitividadCancer Research UKUniversity College LondonNational Institute for Health and Care ResearchU.S. Department of DefenseLon V. Smith FoundationAmerican Association for Cancer ResearchRadboud UniversiteitCanadian Institutes of Health ResearchCancer Institute NSWGeorgia Clinical and Translational Science AllianceUniversity of CambridgeAmerican Cancer SocietyMoffitt Cancer CenterMinnesota Ovarian Cancer AllianceKreftforeningenNational Institute on Minority Health and Health DisparitiesMayo Foundation for Medical Education and ResearchPrincess Margaret Cancer FoundationOregon Health and Science UniversityVanderbilt UniversityAmerican Society of Preventive OncologyMayo ClinicOvarian Cancer Research FundNorth Carolina Central UniversityOak Foundation
KeywordsCalcitriol receptorCYP24A1Single-nucleotide polymorphismSNPBiologyVitamin D and neurologyGenotypingAlleleOdds ratioOncologyGeneticsGenotypeGenome-wide association study1000 Genomes ProjectInternal medicineGeneMedicineEndocrinology

Abstract

fetched live from OpenAlex

Abstract An association between genetic variants in the vitamin D receptor ( VDR ) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets ( EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5 , CYP2R1 , CYP27B1 , CYP24A1 , CYP11A1 , and GC ). Genotyping was performed using the custom‐designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high‐grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 1.2 × 10 −6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6‐3.4, P = 1.6 × 10 −5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 2.3 × 10 −5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.226
Threshold uncertainty score0.875

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.016
GPT teacher head0.270
Teacher spread0.254 · 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 teacher head, 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

Citations7
Published2019
Admission routes2
Has abstractyes

Explore more

Same venueCancer MedicineSame topicOvarian cancer diagnosis and treatmentFrench-language works237,207