Evidence map›Paper›PMID 27978548›Full record

Trial reportJAMA oncology2017

Vitamin D Receptor Genotype, Vitamin D3 Supplementation, and Risk of Colorectal Adenomas: A Randomized Clinical Trial.

Elizabeth L Barry, Janet L Peacock, Judy R Rees, Roberd M Bostick, Douglas J Robertson, Robert S Bresalier, John A Baron

Registry-linked trialOpen access · greenAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in JAMA oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00153816 (Vitamin D/Calcium Polyp Prevention Study), which is not on this map. Cited by 53 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 3 pooled it
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT00153816 phase2 / phase3completednot on this map

Vitamin D/Calcium Polyp Prevention Study

TypeinterventionalSponsorDartmouth-Hitchcock Medical CenterRan2004 to 2016Enrolled2,813ConditionsColorectal Cancer, Polyps, AdenomasArmsCalcium Carbonate, Vitamin D3, placebo
3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 91 citations in OpenAlex.

  1. Pooled it
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  5. No Association Between Vitamin D Supplementation and Risk of Colorectal Adenomas or Serrated Polyps in a Randomized Trial.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 2 countries.

Elizabeth L BarryDepartment of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
Janet L PeacockDivision of Health and Social Care Research, King's College London, London, England.
Judy R ReesDepartment of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
Roberd M BostickRollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, Georgia.
Douglas J RobertsonVA Medical Center, White River Junction, Vermont.
Robert S BresalierDepartment of Gastroenterology, The University of Texas MD Anderson Cancer Center, Houston.
John A BaronDepartment of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire6Department of Medicine, University of North Carolina School of Medicine, Chapel Hill.
Dartmouth College · USEmory University · USKing's College London · GBThe University of Texas MD Anderson Cancer Center · USWhite River Junction VA Medical Center · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
Colorectal Chemoprevention with Calcium and Vitamin DR01CA098286 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARON, JOHN ANTHONY · 2003 to 2015
$43.9M
Relation Between In-utero Vitamin D and Immune Function in Early Childhood P20GM104416 · NIGMS · DARTMOUTH COLLEGE · PI CHRISTENSEN, BROCK CLARKE · 2013 to 2022
$23.7M
Genetic Variants Influencing Response to Vitamin D in Colorectal ChemopreventionR03CA159360 · NCI · DARTMOUTH COLLEGE · PI BARRY, ELIZABETH L · 2011 to 2012
$158k
NCI NIH HHS P30 CA016086NCI NIH HHS P30 CA023108NCI NIH HHS R01 CA098286NCI NIH HHS R03 CA159360NIGMS NIH HHS P20 GM104416
6 · The paper itself

Abstract

importanceDespite epidemiological and preclinical evidence suggesting that vitamin D and calcium inhibit colorectal carcinogenesis, daily supplementation with these nutrients for 3 to 5 years was not found to significantly reduce the risk of recurrent colorectal adenomas in a recent randomized clinical trial.

objectiveTo investigate whether common variants in 7 vitamin D and calcium pathway genes (VDR, GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, and CASR) modify the effects of vitamin D3 or calcium supplementation on colorectal adenoma recurrence. DESIGN, SETTING, AND

participantsWe examined 41 candidate single-nucleotide polymorphisms (SNPs) in 2259 participants in a randomized, double-blind, placebo-controlled trial conducted at 11 clinical centers in the United States. Eligibility criteria included a recently diagnosed adenoma and no remaining colorectal polyps after complete colonoscopy. The study's treatment phase ended on August 31, 2013, and the analysis for the present study took place from July 28, 2014, to October 19, 2016.

interventionsDaily oral supplementation with vitamin D3 (1000 IU) or calcium carbonate (1200 mg elemental calcium) or both or neither. MAIN OUTCOMES AND MEASURES: The outcomes assessed were the occurrence of 1 or more adenomas or advanced adenomas (estimated diameter, ≥1 cm; or with villous histologic findings, high-grade dysplasia, or cancer) during follow-up. Treatment effects and genotype associations and interactions were estimated as adjusted risk ratios (RRs) and 95% confidence intervals (CIs). The effective number of independent SNPs was calculated to correct for multiple testing.

resultsAmong the 2259 participants randomized, 1702 were non-Hispanic whites who completed the trial and had genotype data for analysis (1101 men; mean [SD] age 58.1 [6.8] years). The effect of vitamin D3 supplementation on advanced adenomas, but not on adenoma risk overall, significantly varied according to genotype at 2 VDR SNPs (rs7968585 and rs731236) in linkage disequilibrium (D' = 0.98; r2 = 0.6). For rs7968585, among individuals with the AA genotype (26%), vitamin D3 supplementation reduced risk by 64% (RR, 0.36; 95% CI, 0.19-0.69; P = .002; absolute risk decreased from 14.4% to 5.1%). Among individuals with 1 or 2 G alleles (74%), vitamin D3 supplementation increased risk by 41% (RR, 1.41; 95% CI, 0.99-2.00; P = .05; absolute risk increased from 7.7% to 11.1%; P < .001 for interaction). There were no significant interactions of genotypes with calcium supplementation. CONCLUSIONS AND RELEVANCE: Our findings suggest that benefits from vitamin D3 supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype.

trial registrationclinicaltrials.gov Identifier: NCT00153816.

Indexed as

AdenomaAgedAnticarcinogenic AgentsCalcium CarbonateCholecalciferolColorectal NeoplasmsDietary SupplementsDouble-Blind MethodFemaleGenotypeHumansLinkage DisequilibriumMaleMiddle AgedNeoplasm Recurrence, LocalPolymorphism, Single NucleotideAnticarcinogenic AgentsCalcium CarbonateCholecalciferolReceptors, CalcitriolVDR protein, human

Identifiers

PMID27978548
PMCPMC5580351
OpenAlexW2562762007

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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.