9th Congress of the International Society of Nutrigenetics/Nutrigenomics (ISNN). May 17-19, 2015 Chapel Hill, N.C., USA: Abstracts
Bibliographic record
Abstract
Background/Aims: The vitamin D receptor (VDR) gene polymorphism, Fok1 (rs10735810), may influence risk of cancers via modulation of multiple vitamin D sensitive pathways, including angiogenesis, cell proliferation and differentiation, and protection from oxidative stress.In colorectal cancer (CRC) however, results have been mixed and any association remains contentious [1][2][3][4][5][6][7].Failure to clinically exclude the presence of adenomatous polyps (AP), the benign precursor of CRC, in control cohorts may contribute to the lack of consensus.Insufficient adjustment for other potential risk factors (such as diet, smoking and alcohol intake) may also explain some of the discrepancies.Therefore, we assessed the role of the Fok1 polymorphism in modifying the risk for AP in clinically confirmed cases and controls, adjusting for a range of dietary and lifestyle variables.Methods: Blood was collected from patients undergoing routine colonoscopy (n = 258).Diagnosis of AP was used to classify cases and controls.Fok1 polymorphisms were assessed using RFLP-PCR (F = absence; f = presence of restriction site, early start codon, less transcriptionally active) [8][9].Dietary habits were estimated from food frequency questionnaires.AP incidence (OR, 95% CI) were calculated by genotype, stratified by sex and corrected for age.Additional adjustments were made for life-style factors (smoking history and alcohol intake), objective markers of diet (blood B12 and folate), and reported markers of dietary habits (including estimated dietary fibre, iron, vitamin C, calcium, vitamin D and fat intake).Regression analysis was used to examine the relationship between vitamin D and AP risk.Results: Participants were aged 18-89 (mean 62.25 ± 0.75); 44% were male.AP were detected in 57 (22%) of participants.No statistically significant relationships were found between AP and Fok1 genotype in females.In males the 'F' allele was associated with increased incidence of AP.When adjusted for age only, AP incidence was increased in 'F' homozygotes, relative to 'f' homozygotes (OR = 6.43, 1.09-123.03).Additional adjustment for lifestyle factors revealed increased AP incidence in those possessing the 'F' allele (ORs: FF = 7.59, 1.23-148.70;Ff = 6.42, 1.07-124.68).Further adjustment for dietary variables revealed similar associations.Reported vitamin D intake did not correlate with risk of AP in males or females, regardless of correction for age, smoking status, alcohol consumption or dietary factors (p > 0.05). Conclusion:In Australian males, VDR-Fok1 polymorphisms may influence the risk of AP, the benign precursor to CRC, which in turn, is likely to influence the risk of CRC.Lifestyle & dietary habits influence the strength of this association and need to be fully considered in future studies.This study offers novel insight into the potential for VDR genetics to contribute to risk for adenomatous polyps, and is the first to demonstrate a sex-specific relationship between the VDR-Fok1 polymorphism and risk for adenomatous polyps.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.003 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.076 | 0.038 |
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 source (direct Gemma or distilled Codex), 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".