Bladder Tumor Contains Higher N7-Methylguanine Levels in DNA than Adjacent Normal Bladder Epithelium

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 15; no. 4; pp. 740 - 743
• Main Authors: Saad, Abir A., O'Connor, Peter J., Mostafa, Mostafa H., Metwalli, Nabila E., Cooper, Donald P., Margison, Geoffrey P., Povey, Andrew C.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.2006
• Subjects: Bacterial Infections - complications; Biological and medical sciences; Bladder cancer; DNA Adducts - analysis; DNA Methylation; Egypt; Epithelium - chemistry; Female; Guanine - analogs & derivatives; Guanine - analysis; Humans; Male; Medical sciences; Middle Aged; N7-methylguanine; Nephrology. Urinary tract diseases; Nitrosamines; Schistosoma; Schistosomiasis; Schistosomiasis haematobia - complications; Tumors; Tumors of the urinary system; Urinary Bladder - chemistry; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Urinary tract. Prostate gland; Human; Urinary system disease; Cancerology; DNA; Guanine derivatives; Genetics; Bladder disease; Malignant tumor; Urinary tract disease; Bladder cancer; Carcinogenesis; Molecular adduct
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-05-0813

Schistosoma haematobium –infected patients are more likely to develop bladder cancer and be more exposed to carcinogenic N -nitroso compounds than uninfected patients. As N7-methylguanine is a marker of exposure to methylating agents of this type, we have measured N7-methyldeoxyguanosine 3′-monophosphate (N7-MedGp) by 32 P postlabeling. DNA was isolated from 42 paired normal and tumor tissue of Egyptians with bladder cancer. N7-MedGp was detected in DNA from 93% of the tumors and 74% of the normal bladder tissue samples. Adduct levels were highly variable and ranged from 0.04 to 6.4 and from 0.02 to 0.72 μmol/mol deoxyguanosine 3′-monophosphate (dGp) in tumor and normal DNA, respectively. N7-MedGp levels in normal and tumor DNA were highly correlated with one another ( P = 0.007). The mean difference (95% confidence interval) in adduct levels between tumor and normal DNA was 0.21 (0.13-0.32) μmol/mol dGp and this was statistically significant ( P < 0.001). The adduct ratio (tumor DNA/normal DNA) varied between 0.2 and 136 (median, 4.6). N7-MedGp levels were not associated with gender, age, or the presence of schistosomiasis. However, lower N7-MedGp levels were found in normal DNA from individuals lacking the GSTM1 gene ( P = 0.03) but not the GSTT1 gene or in subjects with the Ile105Val GSTP1 polymorphism. These results show that exposure to methylating agents is widespread and suggest that such exposure may play a role both in tumor initiation and progression. (Cancer Epidemiol Biomarkers Prev 2006;15(4):740–3)