Abstract A49: Meta-analysis of vitamin D-binding protein and cancer risk
Bibliographic record
Abstract
Abstract Antiproliferative effects of 1,25-dihydroxyvitamin D, the biologically active form of vitamin D, are well established in various cell types, including normal and malignant cells, by influencing cell differentiation, cell growth and apoptosis. In addition meta-analyses of epidemiological studies showed that serum 25-hydroxyvitamin D (25OHD) and vitamin D receptors polymorphisms (VDRs) are associated with cancer risk. The biological effects of vitamin D are mediated by an abundance of the vitamin D binding protein (DBP) and VDRs. The gene for the vitamin D–binding protein, known as ‘‘group-specific component’’ (Gc), is also a logical candidate in the vitamin D pathway because its major function is to transport vitamin D metabolites in the blood to different target organs. Variants in this gene have been shown to alter plasma concentrations of 25OHD and several studies investigated Gc SNPs and DBP in association with cancer risk with controversial results. Thus we carried out a comprehensive literature search and meta-analysis to investigate these associations. A systematic literature search was performed following a pre-defined protocol and using validated search strategies up to April 2014. We included for 24 independent studies for a total of 38,331 cases and 25,050 controls, from several countries Australia, Canada and USA, Finland, Germany, the Netherlands, Spain, UK, China and Iran. Data collected concern the following cancer sites: skin (n. of estimates=1), bladder (n=2), breast (n=3), colon-rectum (n=5), endometrium (n=1), liver (n=1), esophagus (n=1), stomach (n=1), melanoma (n= 3), pancreas (n= 2), prostate (n= 5) and kidney (n=1). Through random effect models we calculated the Summary Odd Ratios (SORs) for serum DBP (n. of estimates=6) and the following polymorphisms: rs2282679 (n. of estimates=7), rs12512631 (n=4), rs7041 (n=17), rs4588 (n=12), rs1155563 (n=5) and rs1352844 (n=3). We found a significant 8% increase cancer risk at any site for rs4588 variant (dominant model) and a non significant decrease risk at increasing level of DBP: SOR= 0.94 (0.86-1.02) per an increase of 1000 nmol/L. We evaluated also departure from Hardy-Weinberg equilibrium (HWE) in controls and sensitivity analyses excluding studies that do not respect HWE did not show important changes in results. No indication of publication bias was found. In conclusion we found some interesting associations indicating a possible role of DBP in cancer etiology. Further studies should consider also the role of the ‘free’ unbound part of 25OHD, that drives many of the non-classical actions of vitamin D, and it is dependent on the concentration of DBP. References: -Lauridsen AL, Vestergaard P, Hermann AP, et al. Plasma concentrations of 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D are related to the phenotype of Gc (vitamin D-binding protein): a cross-sectional study on 595 early postmenopausal women. Calcif Tissue Int 2005. -Sinotte M, Diorio C, Berube S, Pollak M, Brisson J. Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women. Am J Clin Nutr 2009. -Gandini S, Boniol M, Haukka J et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011. -Autier P and Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007. -Raimondi S, Johansson H, Maisonneuve P, and Gandini S. Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis. 2009. Citation Format: Sara Gandini, Tagliabue Elena, Sara Raimondi. Meta-analysis of vitamin D-binding protein and cancer risk. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A49.
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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 | 0.005 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".