Polymorphisms in cell cycle regulatory genes, urinary arsenic profile and urothelial carcinoma

Chi Jung Chung, Chi Jung Huang, Yeong Shiau Pu, Chien Tien Su, Yung Kai Huang, Ying Ting Chen, Yu Mei Hsueh

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Introduction: Polymorphisms in p53, p21 and CCND1 could regulate the progression of the cell cycle and might increase the susceptibility to inorganic arsenic-related cancer risk. The goal of our study was to evaluate the roles of cell cycle regulatory gene polymorphisms in the carcinogenesis of arsenic-related urothelial carcinoma (UC). Methods: A hospital-based case-controlled study was conducted to explore the relationships among the urinary arsenic profile, 8-hydroxydeoxyguanosine (8-OHdG) levels, p53 codon 72, p21 codon 31 and CCND1 G870A polymorphisms and UC risk. The urinary arsenic profile was determined using high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). 8-OHdG levels were measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP). Results: Subjects carrying the p21 Arg/Arg genotype had an increased UC risk (age and gender adjusted OR = 1.53; 95% CI, 1.02-2.29). However, there was no association of p53 or CCND1 polymorphisms with UC risk. Significant effects were observed in terms of a combination of the three gene polymorphisms and a cumulative exposure of cigarette smoking, along with the urinary arsenic profile on the UC risk. The higher total arsenic concentration, monomethylarsonic acid percentage (MMA%) and lower dimethylarsinic acid percentage (DMA%), possessed greater gene variant numbers, had a higher UC risk and revealed significant dose-response relationships. However, effects of urinary 8-OHdG levels combined with three gene polymorphisms did not seem to be important for UC risk. Conclusions: The results showed that the variant genotype of p21 might be a predictor of inorganic arsenic-related UC risk.

Original languageEnglish
Pages (from-to)203-209
Number of pages7
JournalToxicology and Applied Pharmacology
Volume232
Issue number2
DOIs
Publication statusPublished - Oct 15 2008

Fingerprint

cdc Genes
Arsenic
Regulator Genes
Polymorphism
Genes
Cells
Carcinoma
Codon
Genotype
Cacodylic Acid
Immunosorbents
Atomic absorption spectrometry
Polymerase chain reaction
High performance liquid chromatography
Dynamic mechanical analysis
Hydrides
Tobacco Products
Assays
Spectrum Analysis
Cell Cycle

Keywords

  • 8-hydroxydeoxyguanine
  • CCND1
  • Cell cycle
  • p21
  • p53
  • Polymorphism
  • Urinary arsenic profile
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Polymorphisms in cell cycle regulatory genes, urinary arsenic profile and urothelial carcinoma. / Chung, Chi Jung; Huang, Chi Jung; Pu, Yeong Shiau; Su, Chien Tien; Huang, Yung Kai; Chen, Ying Ting; Hsueh, Yu Mei.

In: Toxicology and Applied Pharmacology, Vol. 232, No. 2, 15.10.2008, p. 203-209.

Research output: Contribution to journalArticle

Chung, Chi Jung ; Huang, Chi Jung ; Pu, Yeong Shiau ; Su, Chien Tien ; Huang, Yung Kai ; Chen, Ying Ting ; Hsueh, Yu Mei. / Polymorphisms in cell cycle regulatory genes, urinary arsenic profile and urothelial carcinoma. In: Toxicology and Applied Pharmacology. 2008 ; Vol. 232, No. 2. pp. 203-209.
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abstract = "Introduction: Polymorphisms in p53, p21 and CCND1 could regulate the progression of the cell cycle and might increase the susceptibility to inorganic arsenic-related cancer risk. The goal of our study was to evaluate the roles of cell cycle regulatory gene polymorphisms in the carcinogenesis of arsenic-related urothelial carcinoma (UC). Methods: A hospital-based case-controlled study was conducted to explore the relationships among the urinary arsenic profile, 8-hydroxydeoxyguanosine (8-OHdG) levels, p53 codon 72, p21 codon 31 and CCND1 G870A polymorphisms and UC risk. The urinary arsenic profile was determined using high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). 8-OHdG levels were measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP). Results: Subjects carrying the p21 Arg/Arg genotype had an increased UC risk (age and gender adjusted OR = 1.53; 95{\%} CI, 1.02-2.29). However, there was no association of p53 or CCND1 polymorphisms with UC risk. Significant effects were observed in terms of a combination of the three gene polymorphisms and a cumulative exposure of cigarette smoking, along with the urinary arsenic profile on the UC risk. The higher total arsenic concentration, monomethylarsonic acid percentage (MMA{\%}) and lower dimethylarsinic acid percentage (DMA{\%}), possessed greater gene variant numbers, had a higher UC risk and revealed significant dose-response relationships. However, effects of urinary 8-OHdG levels combined with three gene polymorphisms did not seem to be important for UC risk. Conclusions: The results showed that the variant genotype of p21 might be a predictor of inorganic arsenic-related UC risk.",
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AU - Huang, Yung Kai

AU - Chen, Ying Ting

AU - Hsueh, Yu Mei

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