Plasma Metabolites of One-Carbon Metabolism Are Associated With Esophageal Adenocarcinoma in a Population-Based Study
Bibliographic record
Abstract
INTRODUCTION: Esophageal adenocarcinoma (EAC) develops through histopathological stages, including Barrett's esophagus (BE). We analyzed the associations between plasma levels of one-carbon metabolism factors and risks of long-segment BE or EAC. METHODS: Plasma levels were measured from an Irish population-based case-control study (Factors INfluencing the Barrett Adenocarcinoma Relationship study; 204 long-segment BE cases, 211 EAC cases, and 251 controls). A "methyl replete score" was derived by assigning a score of 0 (<median) or 1 (>median) to the levels of 3 dietary methyl donors (methionine, choline, and betaine) and summing across the metabolites. Multinomial logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between EAC or BE and sex-specific quartiles or score using the lowest level as the reference category and adjusted for potential confounders. RESULTS: Highest methionine, betaine, vitamin B6, and choline levels were all associated with 62%-82% reduced risks of EAC ( Ptrends < 0.001). Conversely, S-adenosylmethionine, S-adenosylmethionine/S-adenosylhomocysteine ratio, total homocysteine, and cystathionine were associated with a greater than 2-fold increased EAC risk. A higher methyl replete score was associated with reduced EAC risk (OR 0.33; 95% CI 0.16-0.66). The highest vs lowest plasma methionine levels were borderline statistically significantly associated with long-segment BE (OR 0.55; 95% CI 0.28-1.07), but all other associations were null. DISCUSSION: Several biomarkers of one-carbon metabolism are associated with EAC risk, particularly markers of dietary methyl group donors. Future studies to replicate and prospectively evaluate these markers are warranted.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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)
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".