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; Richard Fedorak; Levinus A Dieleman; Karen Madsen; Remo Panaccione; Subrata Ghosh; Gilaad G Kaplan

doi:10.1016/j.ebiom.2017.06.012

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, Richard Fedorak, Levinus A Dieleman, Karen Madsen, Remo Panaccione, Subrata Ghosh, Gilaad G Kaplan

Immunology and Immunotherapy

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Abstract

BACKGROUND: NOD2 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).

METHODS: Phase 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).

FINDINGS: Phase 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).

INTERPRETATION: The 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.

Original language	English
Pages (from-to)	188-196
Number of pages	9
Journal	EBioMedicine
Volume	21
Early online date	16 Jun 2017
DOIs	https://doi.org/10.1016/j.ebiom.2017.06.012
Publication status	Published - Jul 2017

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Journal Article

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Kuenzig, M. E., Yim, J., Coward, S., Eksteen, B., Seow, C. H., Barnabe, C., Barkema, H. W., Silverberg, M. S., Lakatos, P. L., Beck, P. L., Fedorak, R., Dieleman, L. A., Madsen, K., Panaccione, R., Ghosh, S., & Kaplan, G. G. (2017). 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. EBioMedicine, 21, 188-196. https://doi.org/10.1016/j.ebiom.2017.06.012

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title = "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",

abstract = "BACKGROUND: NOD2 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).METHODS: Phase 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).FINDINGS: Phase 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).INTERPRETATION: The 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.",

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author = "Kuenzig, {M Ellen} and Jeff Yim and Stephanie Coward and Bertus Eksteen and Seow, {Cynthia H} and Cheryl Barnabe and Barkema, {Herman W} and Silverberg, {Mark S} and Lakatos, {Peter L} and Beck, {Paul L} and Richard Fedorak and Dieleman, {Levinus A} and Karen Madsen and Remo Panaccione and Subrata Ghosh and Kaplan, {Gilaad G}",

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doi = "10.1016/j.ebiom.2017.06.012",

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Kuenzig, ME, Yim, J, Coward, S, Eksteen, B, Seow, CH, Barnabe, C, Barkema, HW, Silverberg, MS, Lakatos, PL, Beck, PL, Fedorak, R, Dieleman, LA, Madsen, K, Panaccione, R, Ghosh, S & Kaplan, GG 2017, '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', EBioMedicine, vol. 21, pp. 188-196. https://doi.org/10.1016/j.ebiom.2017.06.012

TY - JOUR

T1 - The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007fs Mutation and may be Explained by Age at Diagnosis

T2 - A Meta-Analysis and Case-Only Study

AU - Kuenzig, M Ellen

AU - Yim, Jeff

AU - Coward, Stephanie

AU - Eksteen, Bertus

AU - Seow, Cynthia H

AU - Barnabe, Cheryl

AU - Barkema, Herman W

AU - Silverberg, Mark S

AU - Lakatos, Peter L

AU - Beck, Paul L

AU - Fedorak, Richard

AU - Dieleman, Levinus A

AU - Madsen, Karen

AU - Panaccione, Remo

AU - Ghosh, Subrata

AU - Kaplan, Gilaad G

PY - 2017/7

Y1 - 2017/7

N2 - BACKGROUND: NOD2 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).METHODS: Phase 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).FINDINGS: Phase 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).INTERPRETATION: The 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.

AB - BACKGROUND: NOD2 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).METHODS: Phase 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).FINDINGS: Phase 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).INTERPRETATION: The 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.

KW - Journal Article

U2 - 10.1016/j.ebiom.2017.06.012

DO - 10.1016/j.ebiom.2017.06.012

M3 - Article

C2 - 28668336

SN - 2352-3964

VL - 21

SP - 188

EP - 196

JO - EBioMedicine

JF - EBioMedicine

ER -

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

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