In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn's disease and non-smokers develop ulcerative colitis

Background and aims: Smoking tobacco has opposite effects on the different forms of inflammatory bowel disease (IBD). It predisposes to the development of Crohn's disease (CID) yet is associated with a reduced incidence of ulcerative colitis (K). We have studied sib pairs discordant for both smoking and IBD phenotype (UC or CID) to investigate whether smoking determines the type of IBD that develops in individuals with very similar genetic susceptibility. Patients: 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 CID (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, CID 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 Switzerland; lihood of needing surgery. However, sib pairs who are discordant for both smoking and IBD type almost always show CID 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 CID. The explana2 tion 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.