Systemic glucocorticoids are potent immunosuppressants, potentially facilitating carcinogenesis. Studies examining glucocorticoids and colorectal cancer risk are few.

To investigate the association between use of systemic glucocorticoids and colorectal cancer risk, both overall and by cancer stage (localised versus metastatic).

We conducted a nested population‐based case–control study in Northern Denmark (1.8 million people) using medical registries. The study included 14 158 patients with a first‐time diagnosis of colorectal cancer from 1991 through 2010. Using risk set sampling, we identified 141 580 population controls, matched on age and gender. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for covariates.

Frequent use of systemic glucocorticoids (defined as >2 prescriptions) was not associated with overall colorectal cancer risk [adjusted OR (aOR) = 0.93 (95% CI: 0.85–1.00)], compared with never/rare use (≤2 prescriptions). Associations according to duration of use and doses (quartiles of cumulative prednisolone equivalents) were also near the null. Examining colorectal cancer by stage, no substantial associations were found between long‐term use (>5 years) of high‐dose (>5500 mg) systemic glucocorticoids and localised [aOR = 1.12 (95% CI: 0.81–1.55)] or metastatic [aOR = 0.82 (95% CI: 0.59–1.14)] cancer.

Despite immunological and metabolic effects of frequent use of systemic glucocorticoids, which would be expected to increase colorectal cancer risk, we found no substantial association between the two.