DNA Methylation and Arsenic-associated Urothelial Carcinoma

The investigators previously pointed out the significant association between urinary arsenic profiles and urothelial carcinoma (UC) risk through a 12-year follow-up study. Further, the investigators observed the increased UC risk in people with lower plasma folate and higher homocysteine than those with higher plasma folate and lower homocysteine in 2010. S-adenosylmethionine (SAM) is one factor included in one-carbon metabolism pathway and is the main donor of methyl group in cells. The ratio of SAM and its metabolite S-adenosylhomocysteine (SAH) not only reflected the intake level of dietary folate but also demonstrated the extent of global DNA methylation. These factors might play important roles in UC carcinogenesis. The investigators would expect to take three years to explore the interactions among global DNA methylation, one-carbon metabolic pathway factors, urinary arsenic profiles, the polymorphisms and haplotype of Glycine N-methyltransferase (GNMT) and UC. In the first year, the investigators would measure the levels of plasma folate, homocysteine, SAM and SAH and evaluate the associations between these factors and UC risk. In the second year, the investigators would set up the method of immunohistochemistry stain and compare the differences between the global DNA methylation from bladder tissues and blood. In the last year, this investigators would analyze the GNMT gene polymorphism and haplotype variation. At the same time, the investigators would explore the impact of GNMT genetic variation and global DNA methylation on UC risk. Based on the results from our research, the investigators might propose that the decreased ratio of SAM/SAH resulted in UC risk increased. This mechanism might be through the changed levels of urinary arsenic profiles and global DNA methylation.