Development of a Non-Invasive DNA Methylation-Based Assay System for the Risk Assessment of Urothelial Carcinoma

NCT ID: NCT00867620

Last Updated: 2009-03-24

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 82 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2010-07-31

Brief Summary

Bladder cancer ranks the ninth in worldwide cancer incidence. Approximate 90% of bladder cancer is the malignancy of urothelium tissues, the urothelial cancer (UC). The mortality of bladder cancer is mainly due to recurrence and metastasis. Unfortunately, the currently available cytology or cystoscopy examination is of limited value because of low sensitivity of early disease. New biomarkers as well as detection technology are thus required to improve early diagnosis. By the aid of quantitative methylation-specific PCR (QMSP), which allows detecting tumor-derived DNA from tissues and body fluids, DNA methylation-based assay is thus developing for early detection and prognosis.

The goal of this proposed project is to develop a panel of DNA-methylation based biomarkers for UC diagnosis, prognosis, and prediction of responses to therapy (especially the recurrence, invasion, survival, and responses to therapeutic agents). Although numerous studies have investigated the aberrant promoter hypermethylation in bladder cancers or UC, inconsistent results are observed. DNA hypermethylation determination may rely on not only the conditions of QMSP, but also the biopsy specimens of different race, environmental expose factors, and regional variation. We thus need to profile the DNA methylation pattern of UC patients in Taiwan to establish a panel of potential prediction biomarkers for local patients.

Detailed Description

In the recent years, technologies of genomics, expression analysis and proteomics have been brought to guide the study of risk assessment and early detection of cancers. This proposed study aims to develop a non-invasive DNA methylation-based assay system elucidating a panel of aberrantly hypermethylated genes from urothelial tumors and urine sediments, to improve the risk assessment of urothelial carcinoma; such as early diagnosis, prognosis, and prediction of response to therapeutic regimes. This proposal will establish several techniques to study the methylation status on gene promoter regions. Three tasks will be achieved in this study: (1) Profiling the aberrant DNA methylation in urothelial carcinoma and determining potential prediction biomarkers. (2) Establishing a non-invasive assay by detecting DNA hypermethylation status in exfoliated cells collected from void urine; (3) Mapping the DNA hypermethylation changes from normal to malignant urothelial tumors and studying the underlying mechanism. Through the collaboration of a genetic toxicologist (Te-Chang Lee, PhD, IBMS), a urologist (Yeong-Shiau Pu, MD/PhD, NTUH) and epidemiologists (Hung-Yi Chiou, PhD, Taipei Medical University), we will explore the risk biomarkers for urothelial carcinoma.

Conditions

Bladder Cancer

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

1

case group: patients with urothelial carcinoma

No interventions assigned to this group

2

control group: those without previous history of any malignancy

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• those with histopathological-confirmed urothelial carcinoma will be included.

Exclusion Criteria

• those were younger than 40 years old or with previous history of any other cancers will be excluded.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Department of Urology / National Taiwan University Hospital

Principal Investigators

HUNG-YI CHIOU, PhD

Role: PRINCIPAL_INVESTIGATOR

COLLEGE OF PUBLIC HEALTH, TAIPEI MEDICAL UNIVERSITY

Yeong-Shiau Pu, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Urology, National Taiwan University Hospital

Te-Chang Lee, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Biomedical Sciences, Academia Sinica

Other Identifiers

200707055R

Identifier Type: -

Identifier Source: org_study_id