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Record W2970157029 · doi:10.1002/ijc.32653

Identification of novel epithelial ovarian cancer loci in women of African ancestry

2019· article· en· W2970157029 on OpenAlexfundno aff
Ani Manichaikul, Lauren C. Peres, Xin‐Qun Wang, Mollie E. Barnard, Deanna Chyn, Xin Sheng, Zhaohui Du, Jonathan P. Tyrer, Joseph Dennis, Ann G. Schwartz, Michele L. Coté, Edward Peters, Patricia G. Moorman, Melissa L. Bondy, Jill S. Barnholtz‐Sloan, Paul Terry, Anthony J. Alberg, Elisa V. Bandera, Ellen Funkhouser, Anna H. Wu, Celeste Leigh Pearce, Malcom Pike, Veronica Wendy Setiawan, Christopher A. Haiman, Julie R. Palmer, Loı̈c Le Marchand, Lynne R. Wilkens, Andrew Berchuck, Jennifer A. Doherty, Francesmary Modugno, Roberta B. Ness, Kirsten B. Moysich, Beth Y. Karlan, Alice S. Whittemore, Valerie McGuire, Weiva Sieh, Kate Lawrenson, Simon A. Gayther, Thomas A. Sellers, Paul D.P. Pharoah, Joellen M. Schildkraut

Bibliographic record

VenueInternational Journal of Cancer · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related molecular mechanisms research
Canadian institutionsnot available
FundersNational Cancer InstituteNational Health and Medical Research CouncilNational Center for Advancing Translational SciencesMedical Research CouncilNational Institutes of HealthNorges ForskningsrådHelse VestMinisterio de Economía y CompetitividadRadboud UniversiteitCanadian Institutes of Health ResearchCancer Institute NSWCancer Research UKWellcome TrustUniversity College LondonNational Institute for Health and Care ResearchU.S. Department of DefenseLon V. Smith FoundationNIHR Cambridge Biomedical Research CentreFred C. and Katherine B. Andersen FoundationUniversity of PittsburghUniversity of CambridgeOregon Health and Science UniversityVanderbilt University Medical CenterMoffitt Cancer CenterMinnesota Ovarian Cancer AllianceKreftforeningenMcGill UniversityMayo Foundation for Medical Education and ResearchEuropean CommissionVanderbilt UniversityOvarian Cancer Research FundNational Center for Research ResourcesRoswell Park Cancer InstituteOak FoundationGeorgia Clinical and Translational Science AllianceGénome Québec
KeywordsBiologySerous fluidSNPOvarian cancerGenome-wide association studyCancerGeneticsBreast cancerOncologySingle-nucleotide polymorphismInternal medicineGenotypeGeneMedicine

Abstract

fetched live from OpenAlex

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome‐wide association study in African ancestry women with 755 EOC cases, including 537 high‐grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC ( p < 1 × 10 −6 ), including rs4525119 (intronic to AKR1C3 ), rs7643459 (intronic to LOC101927394 ), rs4286604 (12 kb 3′ of UGT2A2 ) and rs142091544 (5 kb 5′ of WWC1 ). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5′ of follistatin [ FST ]), rs57403204 (81 kb 3′ of MAGEC1 ), rs79079890 ( LOC105376360 intronic), rs66459581 (5 kb 5′ of PRPSAP1 ), rs116046250 ( GABRG3 intronic) and rs192876988 (32 kb 3′ of GK2 ). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary ( AKR1C3 and FST ), and two are linked to cancer ( AKR1C3 and MAGEC1 ). In follow‐up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women ( p = 0.002), increased risk of ER positive breast cancer in African ancestry women ( p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women ( p = 0.004). A European ancestry‐derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry.

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)0.000
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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.327

Codex and Gemma teacher scores by category

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

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 head0.014
GPT teacher head0.331
Teacher spread0.317 · 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 designBench or experimental
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

Citations28
Published2019
Admission routes1
Has abstractyes

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