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Record W3099497048 · doi:10.1038/s41467-020-19822-6

A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer

2020· article· en· W3099497048 on OpenAlexaff
Mark Gormley, Tom Dudding, Eleanor Sanderson, Richard M. Martin, Steven J. Thomas, Jessica Tyrrell, Paul Brennan, Marcus R. Munafò, Miranda Pring, Stefania Boccia, Andrew F. Olshan, Brenda Diergaarde, Rayjean J. Hung, Geoffrey Liu, George Davey Smith, Rebecca C. Richmond

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsPrincess Margaret Cancer CentreSinai Health SystemLunenfeld-Tanenbaum Research InstitutePublic Health OntarioUniversity of Toronto
FundersNational Institute of Dental and Craniofacial ResearchNational Institute of Environmental Health SciencesProgramme Grants for Applied ResearchMedical Research CouncilUniversity of BristolDiabetes UKDivision of Cancer Epidemiology and Genetics, National Cancer InstituteNational Institute for Health and Care ResearchUniversity of PittsburghNational Cancer InstituteBritish Heart FoundationWellcome TrustWellcomeWorld Health OrganizationCancer Research UKUniversity Hospitals Bristol NHS Foundation TrustNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsMendelian randomizationAlcohol consumptionMedicineCancerRandomizationEnvironmental healthBiologyBioinformaticsGeneticsComputational biologyAlcoholInternal medicineClinical trialGeneGenetic variantsGenotype

Abstract

fetched live from OpenAlex

The independent effects of smoking and alcohol in head and neck cancer are not clear, given the strong association between these risk factors. Their apparent synergistic effect reported in previous observational studies may also underestimate independent effects. Here we report multivariable Mendelian randomization performed in a two-sample approach using summary data on 6,034 oral/oropharyngeal cases and 6,585 controls from a recent genome-wide association study. Our results demonstrate strong evidence for an independent causal effect of smoking on oral/oropharyngeal cancer (IVW OR 2.6, 95% CI = 1.7, 3.9 per standard deviation increase in lifetime smoking behaviour) and an independent causal effect of alcohol consumption when controlling for smoking (IVW OR 2.1, 95% CI = 1.1, 3.8 per standard deviation increase in drinks consumed per week). This suggests the possibility that the causal effect of alcohol may have been underestimated. However, the extent to which alcohol is modified by smoking requires further investigation.

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)0.016
metaresearch head score (Gemma)0.050
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 score0.016
Threshold uncertainty score0.087

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0160.050
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.004
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.045
GPT teacher head0.344
Teacher spread0.299 · 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

Citations143
Published2020
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicGenetic Associations and EpidemiologyFrench-language works237,207