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Record W4414491058 · doi:10.1093/jnci/djaf201

Adiposity distribution and risks of 12 obesity-related cancers: a Mendelian randomization analysis

2025· article· en· W4414491058 on OpenAlexafffund
Emma Hazelwood, Lucy J. Goudswaard, Matthew A. Lee, Marina Vabistsevits, Dimitri J. Pournaras, Hermann Brenner, Daniel D. Buchanan, Stephen B. Gruber, Andrea Gsur, Li Li, Ľudmila Vodičková, Robert C. Grant, N. Jewel Samadder, Nicholas J. Timpson, Marc J. Gunter, Benjamin Schuster‐Böckler, James Yarmolinsky, Tom G. Richardson, Heinz Freisling, Neil Murphy, Emma E. Vincent

Bibliographic record

VenueJNCI Journal of the National Cancer Institute · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsPrincess Margaret Cancer Centre
FundersNational Cancer InstituteMedical Research CouncilCanadian Institutes of Health ResearchWorld Cancer Research FundIpsenInstitut National Du CancerNovo NordiskEisaiGovernment of CanadaUniversity of BristolHorizon 2020 Framework ProgrammeCancer Research UKGenome CanadaIncyteAstraZenecaNational Institutes of HealthWorld Cancer Research Fund InternationalAgentura Pro Zdravotnický Výzkum České RepublikyWorld Health OrganizationEuropean CommissionRoyal College of Surgeons of EnglandPfizer
KeywordsMendelian randomizationBody fat distributionDistribution (mathematics)Adipose tissueFat distributionCancerWeight distribution

Abstract

fetched live from OpenAlex

INTRODUCTION: There is convincing evidence that overall adiposity increases the risks of several cancers. Whether the distribution of adiposity plays a similar role is unclear. METHODS: We used 2-sample Mendelian randomization (MR) to examine causal relationships of 5 adiposity distribution traits (abdominal subcutaneous adipose tissue (ASAT); visceral adipose tissue (VAT); gluteofemoral adipose tissue (GFAT); liver fat; and pancreas fat) with the risks of 12 obesity-related cancers (endometrial, ovarian, breast, colorectal, pancreas, multiple myeloma, liver, kidney (renal cell), thyroid, gallbladder, esophageal adenocarcinoma, and meningioma). RESULTS: Sample size across all genome-wide association studies (GWAS) ranged from 8407 to 728 896 (median: 57 249). We found evidence that higher genetically predicted ASAT increased the risks of endometrial cancer, liver cancer, and esophageal adenocarcinoma (odds ratios (OR) and 95% confidence intervals (CI) per standard deviation (SD) higher ASAT = 1.79 (1.18 to 2.71), 3.83 (1.39 to 10.53), and 2.34 (1.15 to 4.78), respectively). Conversely, we found evidence that higher genetically predicted GFAT decreased the risks of breast cancer and meningioma (ORs and 95% CIs per SD higher genetically predicted GFAT = 0.77 (0.62 to 0.97) and 0.53 (0.32 to 0.90), respectively). We also found evidence for an effect of higher genetically predicted VAT and liver fat on increased liver cancer risk (ORs and 95% CIs per SD higher genetically predicted adiposity trait = 4.29 (1.41 to 13.07) and 4.09 (2.29 to 7.28), respectively). DISCUSSION: Our analyses provide novel insights into the relationship between adiposity distribution and cancer risk. These insights highlight the potential importance of adipose tissue distribution alongside maintaining a healthy weight for cancer prevention.

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)0.030
metaresearch head score (Gemma)0.044
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.030
Threshold uncertainty score0.161

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0300.044
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0020.005
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.000

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 head0.030
GPT teacher head0.340
Teacher spread0.310 · 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 designSimulation or modeling
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

Citations3
Published2025
Admission routes2
Has abstractyes

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