Systemic Glucocorticoid Use and Risk of Colorectal Cancer, Especially Early-Onset Type: A Nationwide Cohort Study.

[BACKGROUND] Evidence on the association between systemic glucocorticoid use and colorectal cancer (CRC) risk is limited. This study aimed to determine whether systemic glucocorticoid use is associated with an increased risk of overall CRC (diagnosed at any age) and early-onset CRC (EOCRC; diagnosed before 50 years of age).

[METHODS] A nationwide cohort study (follow-up: 2005-2018) was conducted using data from multiple nationwide registers in Sweden. The study included 10,921,991 individuals, of whom 2,174,744 used glucocorticoids; among these, 54,443 were newly diagnosed with CRC. The risk of CRC among glucocorticoid users versus nonusers was compared using standardized incidence ratios (SIRs), stratified by medication type and dose.

[RESULTS] Compared with individuals who did not use systemic glucocorticoids, a significantly increased risk of CRC was observed among users of dexamethasone (overall SIR, 2.9; 95% CI, 2.0-4.2; EOCRC SIR, 27; 95% CI, 5.5-79), betamethasone (overall SIR, 1.5; 95% CI, 1.4-1.5; EOCRC SIR, 2.3; 95% CI, 2.0-2.7), prednisolone (overall SIR, 1.2; 95% CI, 1.2-1.3; EOCRC SIR, 1.8; 95% CI, 1.4-2.3), and other systemic glucocorticoids (SIR, 1.4; 95% CI, 1.3-1.5; EOCRC SIR, 2.2; 95% CI, 1.5-3.2). Similar patterns were observed among individuals with a family history of CRC. A high cumulative dose of betamethasone was associated with further increased CRC risk (high-dose tertile SIR, 1.7; 95% CI, 1.6-1.7; medium-dose SIR, 1.3; 95% CI, 1.2-1.4; low-dose SIR, 1.4; 95% CI, 1.3-1.5).

[CONCLUSIONS] Our large-scale cohort study showed that systemic glucocorticoid use is associated with an increased risk of CRC, particularly EOCRC. This study also identifies new high-risk groups who are candidates for earlier, risk-adapted CRC screening or preventive interventions.