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

Abstract

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 (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. 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 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.

Review article: ulcerative colitis, smoking and nicotine therapy

“…In 21 out of the 23 cases, CD developed in the active smoker and UC in the nonsmoker. 46 Similarly, other studies have confirmed the association of smoking with CD and nonsmoking with UC in the context of IBD phenotype expression within families. 47,48 Current smoking has also been demonstrated to exert a deleterious effect on the clinical course of CD after diagnosis.…”

“…10 The risk of smoking to the development of CD may be significantly greater to women than it is to men, with one study demonstrating a threefold relative risk increase. 45 Bridger et al 46 conducted a study involving 87 sibling pairs with IBD who were discordant for smoking status at diagnosis. Of these 87, 23 sibling pairs were also discordant for disease type -one developed UC and the other CD.…”

Inflammatory bowel disease: Genetic and epidemiologic considerations

“…Interestingly, Bridger et al observed that in IBD pedigrees with UC/CD sibling pairs, smokers tend to develop CD and non-smokers UC (O.R. 10.5) [31] . A significant increase in smoking in younger patients with familial CD has been reported [30] .…”

Crohn’s disease as an immunodeficiency

“…Smokers have up to a fivefold increased risk of developing CD [73,74] There is some evidence to suggest that smoking is associated with disruption of the mucus layer [82]. Although this was initially studied (and is likely to be of more relevance) in patients with UC, a similar mechanism may be involved in CD.…”

“…Smokers have up to a fivefold increased risk of developing CD [73,74] and are more likely to have an aggressive clinical course [75] with fistulizing disease and more frequent surgical intervention. Cigarette smoking, and more specifically nicotine, is known to have detrimental effects on the generation of proinflammatory cytokines in patients with CD [76,77], in keeping with the predominantly immunosuppressive effects of smoking on the immune response [78].…”