The Impact of Smoking on Ulcerative Colitis and Interaction With Family History: A Population-Based Cohort Study

Background: The impact of smoking on ulcerative colitis (UC) among Asian populations is controversial, and interactions between genetic factors and smoking are not well studied. We evaluated the association between smoking and UC and assessed interactions between smoking and family history. Methods: Using the National Health Insurance database, we identified 5.5 million individuals from 2002 to 2019 with information on familial relationships and smoking history. Cox proportional hazard regression was used to examine the association between UC and current/former smoking and estimate familial risk. Interactions between family history and smoking were assessed on an additive scale using relative excess risk due to interaction (RERI). Results: Current smoking was associated with a decreased risk of disease (hazard ratio [HR] 0.53 95% CI 0.49–0.56), whereas former smoking was associated with an increased risk (HR 1.62 95% CI 1.53–1.71), compared to nonsmokers. Familial risk was HR 7.51 (95% CI 6.68–8.48). The protective effect of current smoking was more pronounced among those with a family history, as their combined effect was lower than the sum of their individual risks (HR 4.37 vs. 7.55), whereas the harmful effect of former smoking was more prominent among this group, and their combined effect exceeded the sum of their individual effects (HR 10.20 vs. 8.57), indicating statistically significant interactions (RERI current: −3.18 95% CI −4.89 to −1.47; former: 1.63 95% CI −1.00–4.25). Conclusion: The effects of smoking on UC do not appear to differ between Asian and Western populations. Possible gene-smoking interactions were observed but in opposing directions for current/former smoking.