Evidence map›Paper›PMID 28668336›Full record

SynthesisEBioMedicine2017

The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007fs Mutation and may be Explained by Age at Diagnosis: A Meta-Analysis and Case-Only Study.

M Ellen Kuenzig, Jeff Yim, Stephanie Coward, Bertus Eksteen, Cynthia H Seow, Cheryl Barnabe, Herman W Barkema, Mark S Silverberg, Peter L Lakatos, Paul L Beck and 6 more

Abstract readMeta-AnalysisReview
In one paragraph

Synthesis in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. The global burden of inflammatory bowel disease: from 2025 to 2045.Nature reviews. Gastroenterology & hepatology · 2025
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Insight Into Polysaccharides FromFrontiers in immunology · 2021
    Article
  14. Review
  15. The Impact of Inflammatory Bowel Disease in Canada 2018: Children and Adolescents with IBD.Journal of the Canadian Association of Gastroenterology · 2019
    Article
  16. Article
  17. Review
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

16 authors.

M Ellen KuenzigDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Jeff YimFaculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Stephanie CowardDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Bertus EksteenDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Cynthia H SeowDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Cheryl BarnabeDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Herman W BarkemaDepartment of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada; Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Mark S SilverbergZane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Peter L LakatosMcGill University, Montreal General Hospital, Montreal, Quebec, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Paul L BeckDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Richard FedorakDepartment of Medicine, Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Levinus A DielemanDepartment of Medicine, Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Karen MadsenDepartment of Medicine, Division of Gastroenterology and CEGIIR, University of Alberta, Edmonton, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Remo PanaccioneDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Subrata GhoshDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada.
Gilaad G KaplanDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada; Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada; (i)Alberta Inflammatory Bowel Disease Consortium, University of Calgary, Calgary, Alberta, Canada. Electronic address: ggkaplan@ucalgary.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNOD2 and smoking are risk factors for Crohn's disease. We meta-analyzed NOD2-smoking interactions in Crohn's disease (Phase 1), then explored the effect of age at diagnosis on NOD2-smoking interactions (Phase 2).

methodsPhase 1: MEDLINE and EMBASE were searched for studies (n=18) providing data on NOD2 and smoking in Crohn's disease. NOD2-smoking interactions were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) calculated using random effects models. Phase 2: A case-only study compared the proportion of smokers and carriers of the 1007fs variant across ages at diagnosis (≤16, 17-40, >40years).

findingsPhase 1: Having ever smoked was less common among carriers of the 1007fs variant of NOD2 (OR 0.74, 95%CI:0.66-0.83). There was no interaction between smoking and the G908R (OR 0.96, 95%CI:0.82-1.13) or the R702W variant (OR 0.89, 95%CI:0.76-1.05). Phase 2: The proportion of patients (n=627) carrying the 1007fs variant decreased with age at diagnosis (≤16years: 15%; 17-40: 12%; >40: 3%; p=0.003). Smoking was more common in older patients (≤16years: 4%; 17-40: 48%; >40: 71%; p<0.001).

interpretationThe negative NOD2-smoking interaction in Crohn's disease is specific to the 1007fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction.

Indexed as

Gene-Environment InteractionMutationAge FactorsAllelesCase-Control StudiesCrohn DiseaseDisease SusceptibilityFemaleGenotypeHumansMaleNod2 Signaling Adaptor ProteinOdds RatioPolymorphism, Single NucleotidePublication BiasSmokingNOD2 protein, humanNod2 Signaling Adaptor ProteinAgeCigarette smokingCrohn's diseaseGene-environment interactionsNOD2

Identifiers

PMID28668336
PMCPMC5514403

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.