Rheumatoid arthritis and risk of colorectal cancer: a nationwide cohort study

Abstract Objective Prior research on colorectal cancer (CRC) risk in rheumatoid arthritis (RA) lacked analyses incorporating cardiometabolic or behavioral factors, offered limited subsite-specific data, and did not consider RA serostatus. This study assessed the association between RA and subsite-specific CRC risk by RA serostatus. Methods Using the Korean National Health Insurance System database, we identified 40 909 patients with newly diagnosed RA between 2010 and 2017, matched by age and sex at a 1:5 ratio with 204 545 non-RA participants. Multivariable Cox regression models were used to estimate hazard ratio (HR) for the association between RA and CRC incidence. Results During a median follow-up of 5.3 years, 2,174 subjects (319 with RA and 1,855 controls) were diagnosed with CRC. Patients with RA had a decreased risk for CRC compared with non-RA participants (HR, 0.89; 95% confidence intervals [CI], 0.79–0.99). A decreased risk of CRC was found in patients with seronegative RA (HR, 0.79; 95% CI, 0.63–0.98) but not in those with seropositive RA (HR, 0.93; 95% CI, 0.81–1.06). The inverse association between RA and CRC was significant for rectal cancer (HR, 0.63; 95% CI, 0.45–0.87) but not for proximal (HR, 1.04; 95% CI, 0.79–1.39) or distal colon cancer (HR, 0.84; 95% CI, 0.64–1.11). The inverse association between RA and CRC risk was more pronounced in women (HR, 0.80; 95% CI, 0.69–0.94; P for interaction = 0.043). Conclusions Our analyses provide solid evidence of an inverse association between RA and CRC risk, particularly in patients with seronegative RA, rectal cancer cases, and women.