Is smoking an indirect risk factor for the development of ulcerative colitis? An age‐ and sex‐matched case–control study

Abstract
Background: It has been suggested that smoking protects against the development of ulcerative colitis (UC). Evidence is mainly driven from the way data from a multitude of case–control studies have been interpreted. Methods: An age‐ and sex‐matched case–control study was conducted to further assess the association between history of smoking, past surgery, childhood, and other potential causative factors with the development of UC using the answers to a detailed questionnaire. The data were analyzed using univariate analysis and logistic regression. The results are presented as odds ratios (OR) and 95% confidence intervals. Results: One hundred and two cases and an equal number of matched controls were included in the study. Using a three‐level comparison, at the age of diagnosis, the risks of developing UC were 0.41 (0.19–0.87), 3.45 (1.62–7.35) and 0.78 (0.44–1.37) for smokers, ex‐smokers and non‐smokers, respectively. When compared to individuals who have never smoked, ex‐smokers were at a higher risk of developing the disease (OR = 3.00 (1.38–6.51)). The specific history of quitting smoking prior to the age of onset of symptoms was associated with an increased risk for developing the disease (OR = 3.45 (1.62–7.35)). Conclusions: Active smoking was associated with a low risk for the development of UC, but the lack of history of smoking was not associated with an increase in the risk. History of quitting smoking prior to the onset of symptoms, in contrast, was associated with a significant increase in the risk of developing the disease. These findings make the theory of a simple protective effect of smoking on the development of UC difficult to justify. It may be plausible to suggest that the withdrawal of the immunosuppressive effect of smoking triggers the disease onset in a genetically susceptible individual or simply unmasks its symptoms.