DENVER — Prolonged oral glucocorticoid use may be associated with an increased risk of bladder cancer, findings from a new population-based case-control study suggest.
The working hypothesis for the observed association is that the immunosuppression induced by prolonged use of oral glucocorticoids results in diminished immunosurveillance against growing tumors, Dr. Karl Dietrich explained at the annual meeting of the American Association for Cancer Research.
He reported on 786 New Hampshire patients with bladder cancer and 1,083 controls who underwent structured personal interviews regarding their history of medication use as well as the prevalence of standard risk factors for bladder cancer. A total of 61 cancer patients and 51 controls had used oral glucocorticoids for reasons other than organ transplantation for a total of 1 month or more. After adjustment for age, sex, and smoking, current prolonged users of oral glucocorticoids had a 2.2-fold greater risk of bladder cancer than individuals who had not taken the medication for a total of at least 1 month, said Dr. Dietrich of Dartmouth Medical School, Hanover, N.H.
The risk of bladder cancer was greatest in individuals who used oral glucocorticoids for a total of 5 years or more. They had an adjusted 3.4-fold increased risk of the malignancy, compared with nonusers.
Prolonged oral glucocorticoid therapy was more strongly associated with invasive bladder cancer and with tumors having high p53 staining intensity than with noninvasive disease or low-intensity p53 staining.
Prednisone accounted for close to 90% of all oral glucocorticoid use in the study. In all, 63 subjects provided information on the doses used. Those who took at least 50 mg/day had a 4.1-fold increased risk of bladder cancer; however, patients who took less than 10 mg/day or 10-49 mg/day didn't have a significantly greater rate of bladder cancer than did nonusers.
Dr. Dietrich noted in an interview that the bladder cancer study is a sequel to earlier ground-breaking work led by senior investigator Margaret R. Karagas, Ph.D., also of Dartmouth. She had been the lead author of a similar population-based case-control study demonstrating that the use of glucocorticoids for 1 month or longer was associated with an adjusted 2.3-fold increased risk of cutaneous squamous cell carcinoma and a 1.5-fold increased risk of basal cell carcinoma (Br. J. Cancer 2001;85:683-6).
Dr. Karagas was subsequently a coinvestigator in a confirmatory Danish population-based cohort study which concluded that North Jutland County residents with 15 or more filled prescriptions for oral glucocorticoids had a 2.5-fold increased risk of squamous cell carcinoma and a 1.5-fold increased risk of basal cell carcinoma. Individuals with 10-14 prescriptions had a 2.7-fold elevated risk for non-Hodgkin's lymphoma (J. Natl. Cancer Inst. 2004;96:709-11).
The bladder cancer study results suggest that the same glucocorticoid-induced reduction in immunosurveillance that allows growth and development of skin cancers also confers an increased risk of internal malignancies, he said.
The study was partially funded by the National Cancer Institute and the National Institute of Environmental Health Sciences.