BACKGROUND: Bladder cancer cells illustrate major disruptions in their DNA 
methylation patterns as compared with normal ones. Authors aimed to identify 
epigenetic molecular markers in urine for early detection of bladder cancer.
MATERIALS AND METHODS: We retrospectively analyzed the methylation status of 
RARβ(2) and APC genes in urine samples from 210 bladder cancer patients, 61 
patients with benign urological diseases, and 49 healthy volunteers by using 
methylation-specific PCR.
RESULTS: Methylated RARβ(2) and APC were significantly higher in bladder cancer 
patients (62.8%, 59.5%) than benign (16.4%, 5%) but not detected in healthy 
volunteers (0%) at (P < 0.0001). Both methylated genes showed no significant 
difference among clinicopathologic factors; however, they were detected in all 
grades and stages. Among the 128 patients with bilharzial bladder cancer, 94 
(73.4%) showed methylated RARβ(2) and 86 (67.2%) showed methylated APC. 
Homoplasmic methylation pattern of both genes were only detected in bilharzial 
bladder cancer cases. Both sensitivities and specificities of the methylated 
genes for bladder cancer detection were superior to urine cytology and when 
altogether combined, the sensitivities improved to (91.8%), (93.5%), (91.9%), 
and (80.9%) in detection of: bladder cancer, non-muscle invasive bladder cancer, 
low-grade tumors, and bilharzial associated bladder cancer, respectively.
CONCLUSION: Thus, methylated RARβ(2) and APC genes might be valuable urinary 
molecular markers for early detection of bilharzial and nonbilharzial bladder 
cancer.