title: In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn's disease and non-smokers develop ulcerative colitis.
abstract: OBJECTIVE
  Smoking tobacco has opposite effects on the different forms of inflammatory bowel disease (IBD). It predisposes to the development of Crohn's disease (CD) yet is associated with a reduced incidence of ulcerative colitis (UC). We have studied sib pairs discordant for both smoking and IBD phenotype (UC or CD) to investigate whether smoking determines the type of IBD that develops in individuals with very similar genetic susceptibility.
  
  
  METHODS
  Smoking habits and disease characteristics were analysed in 242 IBD pedigrees (658 patients). Within this group there were 339 affected sibling pairs of whom 89 were discordant for smoking when diagnosed.
  
  
  RESULTS
  Smoking at diagnosis was associated with development of CD (odds ratio (OR) 3.55; 95% confidence limits 2.50-5.02; p<0.001) in all of the familial patients, with increases when analysed for ileocaecal disease, fibrostenosis, and intestinal resection. Smokers were also protected from UC (OR 0.28; 0.2-0.4; p<0.001). Of 89 sibling pairs discordant for smoking at diagnosis, 23 were also discordant for disease type-in 21 of these, CD occurred in the smoker and UC in the non-smoker (OR 10.5; 2.6-92; p<0.0001).
  
  
  CONCLUSIONS
  Smoking is a strong environmental risk factor for Crohn's disease and increases the likelihood of needing surgery. However, sib pairs who are discordant for both smoking and IBD type almost always show CD in the smoker and UC in the non-smoker, and so in some cases tobacco consumption acts on IBD genetic predisposition to shift the phenotype from UC towards CD. The explanation of part of the apparent "protective" effect of smoking on sporadic UC may be that the form of IBD that develops in a proportion of smokers is not UC but CD.
authors.affiliation: Department of Medicine, Guy's, King's, and St Thomas's School of Medicine and Dentistry, Bessemer Road, London SE5 9PJ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bridger
authors.forename: J C W
authors.initials: JC
authors.lastname: Lee
authors.forename: I
authors.initials: I
authors.lastname: Bjarnason
authors.forename: J E Lennard
authors.initials: JE
authors.lastname: Jones
authors.forename: A J
authors.initials: AJ
authors.lastname: Macpherson
mesh_terms: D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics / Q000517:prevention & control*; D003424:Crohn Disease / Q000209:etiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007077:Ileal Diseases / Q000235:genetics / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D012907:Smoking / Q000009:adverse effects*