Arsenic Methylation Enzymes, Cigarette Metabolites, DNA Repair Enzymes, Inflammatory Factors and Urothelial Carcinoma

NCT ID: NCT00854464

Last Updated: 2009-03-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

420 participants

Study Classification

OBSERVATIONAL

Study Start Date

2008-08-31

Brief Summary

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1. To investigate the relationship between arsenic methylation enzymes (AS3MT, PNP,GSTO1, and GSTO2) genetic polymorphism and UC risk.
2. To explore the relationship between cigarettes metabolites (NNK, NNAL, HBA, NNAL-Gluc, O6-Methylguanine, and N7-Methylguanine) and UC risk.
3. To examine the relationship between cigarette metabolic enzymes (CYP2A6, CYP2A13, and UGT2B7) genetic polymorphism and UC risk.
4. To elucidate the relationship between DNA repair enzymes (MGMT, XPD, XRCC1, and XRCC3) gene polymorphism and 8-OHdG or between DNA repair enzymes and UC risk.
5. To examine relationship between COX-2 (-1195G/A、-765G/C 和8473C/T), IL-6, IL-8, and TNF-α gene polymorphism and 8-OHdG or between COX-2, IL-6, IL-8, and TNF-α gene polymorphism and UC risk.
6. To examine the risk factors of the environment-environment, gene-environment, and gene-gene interaction on the risk of UC.

Detailed Description

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Urothelial carcinoma (UC) arises exclusively from the urothelium including the renal pelvis,ureter, bladder and urethra, with bladder transitional cell carcinoma (TCC) being the most common form. Arsenic is a well-established human carcinogen of the skin and lung. Recent studies have well documented that the long-term exposure to inorganic arsenic through ingestion and inhalation is associated with an increased risk of bladder cancer, especially TCC.

However, the carcinogenic mechanism of arsenic-induced UC is still unclear. Recently our study found that cigarette smoking interacts with the urinary arsenic profile in modifying the UC risk. In addition, we also found that DNA damage marker 8-hydroxydeoxyguanine (8-OHdG) levels significantly higher in UC patients compared to healthy controls. The mechanism of the interaction between arsenic methylation and cigarette on UC risk is unknown. In addition, whether 8-OHdG is related to DNA repair enzymes or to inflammatory factors or not does need to explore, therefore the specific aims of this project are:

1. To investigate the relationship between arsenic methylation enzymes (AS3MT, PNP, GSTO1, and GSTO2) genetic polymorphism and UC risk.
2. To explore the relationship between cigarettes metabolites (NNK, NNAL, HBA, NNAL-Gluc, O6-Methylguanine, and N7-Methylguanine) and UC risk.
3. To examine the relationship between cigarette metabolic enzymes (CYP2A6, CYP2A13, and UGT2B7) genetic polymorphism and UC risk.
4. To elucidate the relationship between DNA repair enzymes (MGMT, XPD, XRCC1, and XRCC3) gene polymorphism and 8-OHdG or between DNA repair enzymes and UC risk.
5. To examine relationship between COX-2 (-1195G/A、-765G/C 和8473C/T), IL-6, IL-8, and TNF-α gene polymorphism and 8-OHdG or between COX-2, IL-6, IL-8, and TNF-α gene polymorphism and UC risk.
6. To examine the risk factors of the environment-environment, gene-environment, and gene-gene interaction on the risk of UC.

Conditions

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Urothelial Carcinoma

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

* project recruited 420 UC patients in Taiwan University Hospital

Exclusion Criteria

\-
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Taiwan University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Department of Urology / National Taiwan University Hospital

Principal Investigators

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Yeong-Shiau Pu, M.D.PhD.

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

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Department of Urology/National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Yeong-Shiau Pu, M.D. PhD

Role: CONTACT

886-2-23123456 ext. 65249

Other Identifiers

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200809019R

Identifier Type: -

Identifier Source: org_study_id

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