Mutational Landscape and Environmental Effects in Bladder Cancer

Bladder cancer is the most common cancer of the urinary tract. Although nonmuscle-invasive bladder cancers have a good prognosis, muscle-invasive bladder cancers promote metastases and have a poor prognosis. Comprehensive analyses using RNA sequence of clinical tumor samples in bladder cancer have been reported. These reports implicated the candidate genes and pathways that play important roles in carcinogenesis and/or progression of bladder cancer. Further investigations for the function of each mutation are warranted. There is suggestive evidence for several environmental factors as risk factors of bladder cancer. Environmental factors such as cigarette smoking, exposure to chemicals and gases, bladder inflammation due to microbial and parasitic infections, diet, and nutrition could induce several genetic mutations and alter the tumor microenvironment, such as immune cells and fibroblasts. The detailed mechanism of how these environmental factors induce carcinogenesis and/or progression of bladder cancer remains unclear. To identify the relationship between the mutations and the lifestyle could be useful for prevention and treatment of bladder cancer.

Effect of Smoke Exposure on Chronic Inflammation and P53 Expression in Bladder Epithelial

Bladder cancer is widely studied for its association with cigarette smoke (CS) exposure. Nicotine and carcinogenic substances in CS could induce chronic inflammatory state and DNA damage. This research was aimed to investigate the effect of CS exposure in chronic inflammatory state and p53 expression in bladder epithelial of Wistar rats. 25 male Wistar rats aged 6-8 weeks were divided into five groups as follows: Control (without treatment); CS-1, CS-2, CS-4, and CS-8 (treated with CS 1x, 2x, 4x, and 8x/day, respectively). Each exposure was done for 15 minutes for 60 days. Chronic inflammatory score was calculated from HE-stained specimens and Immunohistochemistry method was applied to measure p53 expression. Results showed that lymphocyte and histiocyte count in CS-8 was significantly higher as compared to CS-1 (p<0.05) and control (p<0.05). Lymphocyte and histiocyte count in CS-4 was also significantly higher compared to non-treated group (p<0.05). Chronic inflammatory score was significantly higher in CS-8 compared to other group (p<0.05). Moreover, p53 expression was found in CS-8 group (2 of 5 subjects had positive p53 expression, 20 positive cells in from total 10 hpf) and significantly different with other groups (p=0.011). Correlation study showed significant correlation between frequency of cigarette smoking exposure and lymphocyte count (p=0.000; r=0.956); monocyte count (p=0.000; r=0.928); chronic inflammation score (p=0.000; r=0.928); and p53 expression (p=0.007; r=0.522). We concluded that there was significant differences in chronic inflammation state and p53 expression among groups. Correlation study showed that frequency of cigarette smoking exposure was positively correlated with chronic inflammation and p53 expression.

Effect of Smoke Exposure on Chronic Inflammation and P53 Expression in Pelvis Epithelial

Many risk factors can cause upper urinary tract carcinoma. Smoking is the most influential risk factor and is associated with the formation of aromatic acids and could induce apoptotic cycle. This research was aimed to examine the effect of cigarete smoke exposure on inflammatory state and p53 expression in renal pelvis epithelial of wistar rats. As many as 25 male rats aged 6-8 weeks were divided into five groups as follows: Control (without treatment); CS-1, CS-2, CS-4, and CS-8 (treated with CS 1x, 2x, 4x, and 8x/day, respectively). Each exposure was done for 15 minutes for 60 days. histopathological changes were evaluated from HE-stained specimens and immunohistochemistry method was applied to measure p53 expressio neutrophile and lymphocyte count in CS-8 was significantly higher as compared to CS-1 (p<0.05) and control (p<0.05). p53 expression was found in the CS-8 (3 out of 5 subjects had positive p53 expression, with a total of 4-7 cells from 10 hpf). Correlation study showed significant correlation between frequency of cigarette smoking exposure and neutrophile count (p=0.000; r=-0.856); lymphocyte count (p=0.000; r=0.985); and p53 expression (p=0.000; 0.072). We concluded that there were significant differences in acute inflammation state, chronic inflammation state and p53 expression among groups. Correlation study showed that frequency of cigarette smoking exposure was positively correlated with lymphocyte count and p53 expression.