Vitamin D, calcium, dairy products and genes involved in their metabolic pathways in colorectal cancer risk and survival
Bibliographic record
Abstract
Background Vitamin D, calcium, and dairy products are inversely associated with colorectal cancer incidence. These inverse associations may be mediated by the vitamin D binding protein, the vitamin D receptor (VDR), and the calcium sensing receptor (CASR). The purpose of the thesis was to investigate prediagnostic consumption of vitamin D, calcium, and dairy products and genetic variations in genes involved in their metabolic pathways (GC, VDR, and CASR) for their relevance to colorectal cancer risk and survival in the Newfoundland and Labrador population. Methods A population-based case-control study identified over 700 incident colorectal cancer cases (including 531 patients with follow-up data on mortality end-points) and 489 matched controls. Data on diet and lifestyle factors were gathered via epidemiological questionnaires. Germline DNA samples were genotyped with the Illumina Omni-Quad 1 Million chip in cases and the Affymetrix Axiom® myDesign™ Array in controls. Multivariable logistic regression examined the associations of these nutrients and genetic variants with colorectal cancer risk. Kaplan-Meier curves and Cox models assessed the relationship with overall survival (all-cause mortality, OS) and disease-free survival (DFS) among colorectal cancer patients. Results Results from this study are presented in three related, yet standalone manuscripts: 1) The GC rs2282679 polymorphism was not associated with colorectal cancer risk overall but was correlated with the DFS of colorectal cancer patients (per C allele HR, 1.36; 95% CI, 1.05- 1.77). The association of this SNP on DFS was limited to BRAF wild-type tumors. 2) VDR and CASR genes were associated with DFS and OS of colorectal cancer, respectively, at the gene level. Haplotype analysis within linkage blocks of CASR revealed the G-G-G-G-G-A- C haplotype (rs10222633-rs10934578-rs3804592-rs17250717-A986S-R990G-rs1802757) to be associated with a decreased OS of colon cancer (HR, 3.15; 95% CI, 1.66-5.96). 3) Prediagnostic calcium intake from foods, but not total calcium intake, was negatively associated with all-cause mortality (HR for Q2 vs. Q1, 0.44; 95% CI, 0.26-0.75). An inverse relationship was also seen in a dose-response fashion for prediagnostic cheese intake (P trend=0.029). No evidence for modification by factors known to be associated with colorectal cancer survival was observed. Conclusions Our results indicate that genetic variations in GC, VDR and CASR genes are associated with survival after colorectal cancer diagnosis. These findings also suggest a protective role of prediagnostic intakes of cheese and calcium from foods against colorectal cancer progression.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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 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".