Introduction
Microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is a chronic inflammatory condition of the colon. Due to historical underdiagnosis, the long-term risks of cancer and mortality in MC remain incompletely understood.
Aims & Methods
We aimed to assess the risks of all-cause mortality and cancer in individuals with MC in Sweden between 1990 and 2023, using the ESPRESSO histopathology cohort, which includes all individuals with incident, biopsy-confirmed MC. Each patient was matched to up to five general population comparators based on age, sex, calendar year, and county of residence. Follow-up extended through December 31, 2023 and outcomes were ascertained from Swedish healthcare registers. For the mortality analysis, we included all individuals with MC regardless of prior diagnoses, to better reflect the real-world burden of comorbidities. The primary outcome was all-cause mortality. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. The model was adjusted for the matching variables, educational attainment, history of inflammatory bowel disease, and overall comorbidity burden using the Charlson Comorbidity Index. For the cancer analysis, individuals with a history of cancer (excluding non-melanoma skin cancer) or IBD prior to cohort entry were excluded to reduce confounding and to to ensure capture of new-onset malignancies. The primary outcome was any incident cancer, with secondary outcomes including site-specific cancers. Cox models were used to estimate aHRs, adjusting for the matching variables, educational attainment, celiac disease, type 1 diabetes, and chronic obstructive pulmonary disease (as a proxy for smoking).
Results
The mortality analysis included 23,760 MC patients and 113,362 matched comparators. After adjustment for the matching variables, MC was associated with increased all-cause mortality (aHR 1.16, 95% CI 1.13–1.20). Further adjustment for comorbidities attenuated the association, though it remained statistically significant (aHR 1.08, 95% CI 1.05–1.11). In stratified analyses, CC showed a significantly stronger association with increased mortality (aHR 1.15, 95% CI 1.10–1.20) compared with LC (aHR 1.05, 95% CI 1.01–1.08; pheterogeneity = 0.0009).
The cancer analysis included 18,497 MC patients and 79,832 matched population comparators. MC was associated with a modest increase in overall cancer risk (aHR 1.07, 95% CI 1.02–1.12). Site-specific analyses showed increased risks of lymphoma (aHR 1.29, 95% CI 1.03–1.61) and lung cancer (aHR 1.32, 95% CI 1.12–1.57), no association with breast cancer (aHR 0.99, 95% CI 0.88–1.12), and reduced risks of colorectal cancer (aHR 0.55, 95% CI 0.46–0.66) and gastrointestinal cancer overall (aHR 0.78, 95% CI 0.69–0.88). The aHRs for CC and LC were comparable with respect to overall cancer risk.
Conclusion
In this large, nationwide cohort study with follow-up through December 2023, MC was associated with modest increases in both all-cause mortality and incident cancer. The elevated overall cancer risk may reflect residual confounding; however, the substantially reduced risk of colorectal cancer is reassuring and reaffirms that routine colorectal cancer screening may be unwarranted in patients with MC. The excess mortality appears to be partly driven by comorbidities. While enhanced cancer screening beyond general population guidelines may not be necessary, our findings highlight the importance of identifying and managing comorbid conditions as part of the long-term care of patients with MC.
Disclosure
FE has served as an advisory board member for Boehringer Ingelheim.
JFL has coordinated a study on behalf of the Swedish IBD quality register (SWIBREG). That study received funding from Janssen Corporation. JFL has also received financial support from MSD/Merck developing a paper reviewing national healthcare registers in China, and for a collaboration on inflammatory bowel disease. JFL also has a research collaboration on celiac disease with Takeda.
DSP has received research support from Rise Therapeutics, Seres Therapeutic, Exe GI Pharma LLC, Vedanta Biosciences inc, Pfizer, Applied Molecular Transport, Janssen, and Takeda and consulting fees from Rebiotics Therapeutics, Rise Therapeutics, Seres Therapeutics, Exe GI Pharma LLC, Vedanta Biosciences inc, Immunic, Merck, Ferring, Boehringer Ingelheim, and Lilly.