Brief Title
DNA Methylation and Arsenic-associated Urothelial Carcinoma
Official Title
Comparison of DNA Methylation Between Urothelial Carcinoma and Healthy Controls
Brief Summary
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.
Study Type
Observational
Primary Outcome
urothelial carcinoma
Condition
Urothelial Carcinoma
Study Arms / Comparison Groups
urothelial carcinoma
Description: Pathological verification of UC was done by routine urological practice including endoscopic biopsy or surgical resection of urinary tract tumors followed by histopathological examination by board-certified pathologists.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
600
Start Date
May 2011
Primary Completion Date
May 2014
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of urothelial carcinoma
- The voluntary of participating the study
Exclusion Criteria:
- Age smaller than 20 years
- Pregnant women
- Not willing to participate the study because of their personal reasons
Gender
All
Ages
21 Years - N/A
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Chi-Jung Chung, PhD, 886-4-22052121, [email protected]
Location Countries
Taiwan
Location Countries
Taiwan
Administrative Informations
NCT ID
NCT01360723
Organization ID
DMR100-IRB-080
Study Sponsor
China Medical University Hospital
Study Sponsor
Chi-Jung Chung, PhD, Principal Investigator, Department of Health risk Management, China Medical University
Verification Date
May 2011