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Record W2802060268 · doi:10.1158/0008-5472.can-17-2900

HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes

2018· article· en· W2802060268 on OpenAlexafffund
Sophia Wang, Mary Carrington, Sonja I. Berndt, Susan L. Slager, Paige M. Bracci, Jenna Voutsinas, James R. Cerhan, Karin E. Smedby, Henrik Hjalgrim, Joseph Vijai, Lindsay M. Morton, Roel Vermeulen, Ora Paltiel, Claire M. Vajdic, Martha S. Linet, Alexandra Nieters, Sílvia de Sanjosé, Wendy Cozen, Elizabeth E. Brown, Jennifer Turner, John J. Spinelli, Tongzhang Zheng, Brenda M. Birmann, Christopher R. Flowers, Nikolaus Becker, Elizabeth A. Holly, Eleanor Kane, Dennis D. Weisenburger, Marc Maynadié, Pierluigi Cocco, Demetrius Albanes, Stephanie J. Weinstein, Lauren R. Teras, W. Ryan Diver, S. Lax, Ruth C. Travis, Rudolph Kaaks, Elio Ríboli, Yolanda Benavente, Paul Brennan, James McKay, Marie‐Hélène Delfau‐Larue, Brian K. Link, Corrado Magnani, Maria Grazia Ennas, Giancarlo Latte, Andrew L. Feldman, Nicole Wong Doo, Graham G. Giles, Melissa C. Southey, Roger L. Milne, Kenneth Offit, Jacob Musinsky, Alan A. Arslan, Mark P. Purdue, Hans‐Olov Adami, Mads Melbye, Bengt Glimelius, Lucía Conde, Nicola J. Camp, Martha Glenn, Karen Curtin, Jacqueline Clavel, Alain Monnereau, David G. Cox, Hervé Ghesquières, Gilles Salles, Paulo Bofetta, Lenka Foretová, Anthony Staines, S. Scott Davis, Richard K. Severson, Qing Lan, Angela Brooks‐Wilson, Martyn T. Smith, Eve Roman, Anne Kricker, Yawei Zhang, Peter Kraft, Stephen J. Chanock, Nathaniel Rothman, Patricia Hartge, Christine F. Skibola

Bibliographic record

VenueCancer Research · 2018
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsSimon Fraser UniversityUniversity of British ColumbiaBC Cancer Agency
FundersNational Center for Chronic Disease Prevention and Health PromotionNational Institute of Environmental Health SciencesNational Cancer InstituteCancer Council VictoriaNational Human Genome Research InstituteCancer Council NSWMedical Research CouncilInstitut National Du CancerCenters for Disease Control and PreventionNational Institutes of HealthCancer Research UKBlood Cancer UKAgence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du TravailCancerfondenBundesamt für StrahlenschutzLeukemia and Lymphoma ResearchNational Health and Medical Research CouncilU.S. Public Health ServiceRegione Autonoma della SardegnaAssociazione Italiana per la Ricerca sul CancroUniversity of UtahFondation de FranceGeneralitat de CatalunyaCanadian Institutes of Health ResearchBundesministerium für Bildung und ForschungLeukaemia and Lymphoma ResearchMinisterstvo Školství, Mládeže a TělovýchovyWorld Health OrganizationUniversity of Southern CaliforniaUniversity of SydneyStockholms Läns LandstingUtah Department of HealthLeukemia and Lymphoma SocietyHealth Research BoardJosé Carreras Leukämie-StiftungU.S. Department of Health and Human ServicesMayo ClinicUniversity of California, San FranciscoFrederick National Laboratory for Cancer ResearchYale UniversityKarolinska InstitutetUtah State UniversityHuntsman Cancer InstituteEuropean CommissionCompagnia di San PaoloU.S. Department of Veterans AffairsMichael Smith Health Research BCMemorial Sloan-Kettering Cancer Center
KeywordsHuman leukocyte antigenLymphomaHodgkin lymphomaImmunologyBiologyGeneticsMedicineAntigen

Abstract

fetched live from OpenAlex

Abstract A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.286
Threshold uncertainty score0.730

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0000.001
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 head0.052
GPT teacher head0.352
Teacher spread0.300 · 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".

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Citations42
Published2018
Admission routes2
Has abstractyes

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