An envirogenomic signature is associated with risk of IBD-related surgery in a population-based Crohn's disease cohort

J Gastrointest Surg. 2013 Sep;17(9):1643-50. doi: 10.1007/s11605-013-2250-1. Epub 2013 Jul 2.

Abstract

Background and aims: Crohn's disease (CD) is an inflammatory bowel disease (IBD) caused by a combination of genetic, clinical, and environmental factors. Identification of CD patients at high risk of requiring surgery may assist clinicians to decide on a top-down or step-up treatment approach.

Methods: We conducted a retrospective case-control analysis of a population-based cohort of 503 CD patients. A regression-based data reduction approach was used to systematically analyse 63 genomic, clinical and environmental factors for association with IBD-related surgery as the primary outcome variable.

Results: A multi-factor model was identified that yielded the highest predictive accuracy for need for surgery. The factors included in the model were the NOD2 genotype (OR = 1.607, P = 2.3 × 10(-5)), having ever had perianal disease (OR = 2.847, P = 4 × 10(-6)), being post-diagnosis smokers (OR = 6.312, P = 7.4 × 10(-3)), being an ex-smoker at diagnosis (OR = 2.405, P = 1.1 × 10(-3)) and age (OR = 1.012, P = 4.4 × 10(-3)). Diagnostic testing for this multi-factor model produced an area under the curve of 0.681 (P = 1 × 10(-4)) and an odds ratio of 3.169, (95% CI P = 1 × 10(-4)) which was higher than any factor considered independently.

Conclusions: The results of this study require validation in other populations but represent a step forward in the development of more accurate prognostic tests for clinicians to prescribe the most optimal treatment approach for complicated CD patients.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Case-Control Studies
  • Cohort Studies
  • Crohn Disease / etiology
  • Crohn Disease / surgery*
  • Decision Support Techniques*
  • Diet
  • Environment*
  • Female
  • Genetic Markers
  • Genotype*
  • Humans
  • Life Style*
  • Logistic Models
  • Male
  • Middle Aged
  • Nod2 Signaling Adaptor Protein / genetics
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • ROC Curve
  • Retrospective Studies
  • Risk Factors
  • Smoking / adverse effects

Substances

  • Genetic Markers
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein