Trial reportBMC medicine2018
Exploring causality in the association between circulating 25-hydroxyvitamin D and colorectal cancer risk: a large Mendelian randomisation study.
Trial report in BMC medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 8 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Vitamin D and human health: evidence from Mendelian randomization studies.European journal of epidemiology · 2024Pooled it
- Serum 25-Hydroxyvitamin D and Cancer Risk: A Systematic Review of Mendelian Randomization Studies.Nutrients · 2023Pooled it
- Vitamin D supplementation and total cancer incidence and mortality by daily vs. infrequent large-bolus dosing strategies: a meta-analysis of randomised controlled trials.British journal of cancer · 2022Pooled it
- Vitamin D and Multiple Health Outcomes: An Umbrella Review of Observational Studies, Randomized Controlled Trials, and Mendelian Randomization Studies.Advances in nutrition (Bethesda, Md.) · 2022Pooled it
- Systematic review of Mendelian randomization studies on risk of cancer.BMC medicine · 2022Pooled it
- The effect of vitamin D supplementation on survival in patients with colorectal cancer: systematic review and meta-analysis of randomised controlled trials.British journal of cancer · 2020Pooled it
- Non-genetic biomarkers and colorectal cancer risk: Umbrella review and evidence triangulation.Cancer medicine · 2020Pooled it
- Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials.Annals of oncology : official journal of the European Society for Medical Oncology · 2019Pooled it
- Vitamin D in Gut and Systemic Immune Tolerance and in Infections' Risk: An International Evidence-Based Consensus Statement.Reviews in endocrine & metabolic disorders · 2026Review
- Integrative oncology in colorectal cancer: evidence-based strategies from prevention through survivorship.Frontiers in oncology · 2026Review
- Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation.British journal of cancer · 2024Article
- Falsification of the instrumental variable conditions in Mendelian randomization studies in the UK Biobank.European journal of epidemiology · 2023Article
- Vitamin D: Can Gender Medicine Have a Role?Biomedicines · 2023Review
- Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases.Frontiers in nutrition · 2023Review
- Vitamin D and Systems Biology.Nutrients · 2022Review
- New Insights into Bile Acids Related Signaling Pathways in the Onset of Colorectal Cancer.Nutrients · 2022Review
- Vitamin D receptor absence does not enhance intestinal tumorigenesis in ApcPirc/+rats.Biology open · 2022Article
- Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer.Cancer causes & control : CCC · 2022Article
- The health effects of vitamin D supplementation: evidence from human studies.Nature reviews. Endocrinology · 2022Review
- Oral vitamin D supplementation induces transcriptomic changes in rectal mucosa that are linked to anti-tumour effects.BMC medicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 13 institutions in 8 countries.
Funding
Abstract
backgroundWhilst observational studies establish that lower plasma 25-hydroxyvitamin D (25-OHD) levels are associated with higher risk of colorectal cancer (CRC), establishing causality has proven challenging. Since vitamin D is modifiable, these observations have substantial clinical and public health implications. Indeed, many health agencies already recommend supplemental vitamin D. Here, we explore causality in a large Mendelian randomisation (MR) study using an improved genetic instrument for circulating 25-OHD.
methodsWe developed a weighted genetic score for circulating 25-OHD using six genetic variants that we recently reported to be associated with circulating 25-OHD in a large genome-wide association study (GWAS) meta-analysis. Using this score as instrumental variable in MR analyses, we sought to determine whether circulating 25-OHD is causally linked with CRC risk. We conducted MR analysis using individual-level data from 10,725 CRC cases and 30,794 controls (Scotland, UK Biobank and Croatia). We then applied estimates from meta-analysis of 11 GWAS of CRC risk (18,967 cases; 48,168 controls) in a summary statistics MR approach.
resultsThe new genetic score for 25-OHD was strongly associated with measured plasma 25-OHD levels in 2821 healthy Scottish controls (P = 1.47 × 10
conclusionsDespite the scale of this study and employing an improved score capturing more of the genetic contribution to circulating 25-OHD, we found no evidence for a causal relationship between circulating 25-OHD and CRC risk. Although the magnitude of effect for vitamin D suggested by observational studies can confidently be excluded, smaller effects sizes and non-linear relationships remain plausible. Circulating vitamin D may be a CRC biomarker, but a causal effect on CRC risk remains unproven.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.