XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma

Chien I. Chiang, Ya Li Huang, Wei Jen Chen, Horng Sheng Shiue, Chao Yuan Huang, Yeong Shiau Pu, Ying-Chin Lin, Yu Mei Hsueh

Research output: Contribution to journalArticle

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Abstract

The association between DNA repair gene polymorphisms and bladder cancer has been widely studied. However, few studies have examined the correlation between urothelial carcinoma (UC) and arsenic or its metabolites. The aim of this study was to examine the association between polymorphisms of the DNA repair genes, XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln, with urinary arsenic profiles and UC. To this end, we conducted a hospital-based case-control study with 324 UC patients and 647 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln by PCR-restriction fragment length polymorphism analysis (PCR-RFLP). Urinary arsenic profiles were measured by high performance liquid chromatography (HPLC) linked with hydride generator and atomic absorption spectrometry. The XRCC1 399 Gln/. Gln and 194 Arg/. Trp and Trp/. Trp genotypes were significantly related to UC, and the odds ratio (OR) and 95% confidence interval (95%CI) were 1.68 (1.03-2.75) and 0.66 (0.48-0.90), respectively. Participants with higher total urinary arsenic levels, a higher percentage of inorganic arsenic (InAs%) and a lower percentage of dimethylarsinic acid (DMA%) had a higher OR of UC. Participants carrying XRCC1 risk diplotypes G-C/G-C, A-C/A-C, and A-T/G-T, and who had higher total arsenic levels, higher InAs%, or lower DMA% compared to those with other XRCC1 diplotypes had a higher OR of UC. Our results suggest that the XRCC1 399 Gln/. Gln and 194 Arg/. Arg DNA repair genes play an important role in poor arsenic methylation capacity, thereby increasing the risk of UC in non-obvious arsenic exposure areas.

Original languageEnglish
Pages (from-to)373-379
Number of pages7
JournalToxicology and Applied Pharmacology
Volume279
Issue number3
DOIs
Publication statusPublished - Jul 10 2014

Fingerprint

Methylation
Arsenic
Polymorphism
Carcinoma
Cacodylic Acid
DNA Repair
Repair
Genes
DNA
Odds Ratio
Genotype
Association reactions
Atomic absorption spectrometry
High performance liquid chromatography
Metabolites
Urinary Bladder Neoplasms
Hydrides
Restriction Fragment Length Polymorphisms
Case-Control Studies
Spectrum Analysis

Keywords

  • Arsenic
  • Arsenic methylation capacity
  • Polymorphism
  • Urothelial carcinoma
  • XRCC1

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma. / Chiang, Chien I.; Huang, Ya Li; Chen, Wei Jen; Shiue, Horng Sheng; Huang, Chao Yuan; Pu, Yeong Shiau; Lin, Ying-Chin; Hsueh, Yu Mei.

In: Toxicology and Applied Pharmacology, Vol. 279, No. 3, 10.07.2014, p. 373-379.

Research output: Contribution to journalArticle

Chiang, Chien I. ; Huang, Ya Li ; Chen, Wei Jen ; Shiue, Horng Sheng ; Huang, Chao Yuan ; Pu, Yeong Shiau ; Lin, Ying-Chin ; Hsueh, Yu Mei. / XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma. In: Toxicology and Applied Pharmacology. 2014 ; Vol. 279, No. 3. pp. 373-379.
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