Mendelian Randomization of Circulating Polyunsaturated Fatty Acids and Colorectal Cancer Risk
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
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.
- Candidate categories
- none
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: ObservationalConsensus signal: Observational
- Genre
- Candidate signal: EmpiricalConsensus signal: Empirical
- Teacher disagreement score
- 0.046
- Threshold uncertainty score
- 0.668
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.300 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Abstract Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93–0.98; P = 5.2 × 10−4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92–0.97; P = 5.4 × 10−5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03–1.08; P = 3.3 × 10−5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01–1.07; P = 2.5 × 10−3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01–1.06; P = 1.2 × 10−2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.
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.
The record
- Venue
- Cancer Epidemiology Biomarkers & Prevention
- Topic
- Inflammatory mediators and NSAID effects
- Field
- Medicine
- Canadian institutions
- Memorial University of NewfoundlandOntario Institute for Cancer ResearchCancer Care Ontario
- Funders
- National Institute of Environmental Health SciencesNational Cancer InstituteNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteNational Health and Medical Research CouncilConseil Régional des Pays de la LoireU.S. Public Health ServiceU.S. Department of Health and Human ServicesDHHS Office of the SecretaryGroupement des Entreprises Françaises dans la lutte contre le CancerConsejería de Educación, Junta de Castilla y LeónVetenskapsrådetMedical Research CouncilSwedish Cancer FoundationAssociation Anne de Bretagne GenetiqueCanadian Institutes of Health ResearchCalifornia Department of Public HealthMatthias Lackas-StiftungStockholms Läns LandstingDivision of Cancer Prevention, National Cancer InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesMoffitt Cancer CenterWorld Health OrganizationCancer Research UKAmerican Cancer SocietyInstituto de Salud Carlos IIIXarxa de Bancs de Tumors de CatalunyaCanadian Cancer Society Research InstituteNational Institutes of HealthJunta de Castilla y León
- Keywords
- Mendelian randomizationColorectal cancerMedicineInternal medicinePolyunsaturated fatty acidAspirinDocosapentaenoic acidConfoundingEicosapentaenoic acidOncologyGenome-wide association studyConfidence intervalLower riskCancerSingle-nucleotide polymorphismEndocrinologyBiologyGeneticsGenotypeFatty acidGeneBiochemistryGenetic variants
- Has abstract in OpenAlex
- yes