Active and passive cigarette smoke exposure increased the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD), and including this risk factor would improve current risk stratification for surveillance strategies for colorectal neoplasia, according to a novel cohort study from the Netherlands.
By IBD type, past smoking increased the colorectal neoplasia risk in ulcerative colitis (UC), with a hazard ratio (HR) of 1.73 (95% CI 1.05-2.85), while passive smoke exposure had no impact, reported Kimberley W.J. van der Sloot, MD, and colleagues from the University of Groningen. For Crohn’s disease (CD), both active smoking and passive smoke exposure significantly increased risk — HR 2.20 (95% CI 1.02-4.76) and 1.87 (1.09-3.20), respectively.
IBD patients are already at increased risk of colorectal neoplasia owing to mucosal inflammation, the researchers noted in their study online in Clinical Gastroenterology and Hepatology.
Smoking is also thought to increase the likelihood of having a severe phenotype of CD with structuring or penetrating disease, the team added. “As current surveillance guidelines form a burden on patients and healthcare costs, stratification of high-risk patients is crucial.”
Cigarette smoke reduces inflammation in UC (but not CD) and is a known risk factor for colorectal neoplasia in the general population, in which the decline in colorectal cancer may be partly due to the decline in smoking, the authors noted.
The effect of smoking on colorectal neoplasia in IBD specifically, however, has been unclear. In the new study, the first to assess the potential impact of tobacco smoke in this group of patients, the retrospective analysis reviewed all patients (total of 1,386) treated at a single tertiary-care hospital’s IBD center. All had previous biopsies analyzed and reported in a nationwide pathology register, and patients’ clinical features and exposure to cigarette smoke were evaluated.
In this cohort, 153 patients (11.5%) developed colorectal neoplasia, and of these, 11 (7.2%) had colorectal cancer, 12 (7.8%) had high-grade dysplasia, and 130 (85.0%) had low-grade dysplasia.
Participants eligible for surveillance (disease duration longer than years) were then stratified for dysplasia risk according to European Crohn’s and Colitis Organization and European Society of Gastrointestinal and Abdominal Radiology guidelines, and Cox regression modeling was used to estimate the effect of cigarette smoke exposure and its possible additive effect within the current risk stratification framework.
The researchers used likelihood-ratio tests to analyze the additive predictive effect of cigarette, and the model assumptions were met. Previously described risk factors, such as a first-degree family member with colorectal neoplasia in CD (P=0.001) and the presence of post-inflammatory polyps in UC (P=0.005), were replicated. When smoke exposure was added to the current risk-stratification model, the model fit for CD was significantly improved, the researchers reported.
They noted that previous studies have suggested that, regardless of the decreasing trend of colorectal carcinomas, the risk of colorectal neoplasia seems to remain high in certain subgroups. “Based on the results in the current study, one could identify patients with CD, exposed to cigarette smoking, to be part of this high-risk group,” van der Sloot and co-authors stated. “Knowing the proven effect of advocating smoking cessation in decreasing risk of flares in CD, further efforts in aiding smoking cessation during clinical practice might also influence future risk of [colorectal neoplasia].”
The researchers advised that future, optimally larger, studies should evaluate the role of cigarette smoke exposure in more detail, including the possible dose-dependent effect of pack years as described in the general population, as well as other lifestyle-associated factors such as alcohol consumption, physical activity, and fresh produce consumption.
Study limitations, the team said, included the reliance on data from a single, tertiary-care IBD clinic, given that the baseline risk of colorectal neoplasia seems to be higher in IBD patients treated at such centers compared with those in population-based studies. Validation of the findings in peripheral hospitals is needed, the researchers added.
Van der Sloot was supported by a grant from the University of Groningen; one co-author reported financial relationships with Takeda, Johnson & Johnson, Tramedico, and Ferring; and another reported financial relationships with AbbVie, Takeda and Ferring, Mundipharma, Pharmacosmos, Takeda, and Janssen.