Polymorphisms of arsenic (13 Oxidation State) methyltransferase and arsenic methylation capacity affect the risk of bladder cancer

Ying Chin Lin, Wei Jen Chen, Chao Yuan Huang, Horng Sheng Shiue, Chien Tien Su, Pui Lam Ao, Yeong Shiau Pu, Yu Mei Hsueh

Research output: Contribution to journalArticle

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Abstract

The mechanisms underlying how arsenicmethylation capacity affects bladder cancer (BC) are still unclear. The objective of this study was to explore the effects of polymorphisms of arsenic (+3 oxidation state) methyltransferase (AS3MT) on BC risk. We conducted a hospital-based study and enrolled 216 BC and 648 healthy controls from2007 to 2011. Urinary arsenic profiles weremeasured using high-performance liquid chromatography-hydride generation-atomic absorption spectrometry. The gene polymorphisms of AS3MT were identified using the SequenomMassARRAY platform with iPLEX Gold chemistry. Inefficient arsenicmethylation capacity (highmonomethylarsonic acid percentage [MMA%] and low dimethylarsinic acid percentage [DMA%]) was associated with increased risk of BC in a dose-response relationship. AS3MT rs11191438 (C > G) G/G genotype, AS3MT rs10748835 (A > G) G/G genotype, and AS3MT rs1046778 (C > T) T/T genotype were found to be related to BC risk, where the odds ratio (OR) (95% CI) was 0.50 (0.31-0.82), 0.49 (0.30-0.79), and 0.54 (0.36-0.80), respectively. The combination of AS3MT haplotype 2 (AS3MT rs11191453, rs11191454, rs10748835, and rs1046778)'s high-risk haplotype (C-G-A-C, T-A-A-C, and T-G-G-T) was significantly associated with increased risk of BC. Among controls, only 3 of the 9 candidate genotypes evaluated, rs1119438 C/C, rs10748835 A/A and rs1046778 C/C, were associated with significantly higherMMA% compared with the other genotypes. No other genotypes or haplotypes were related to arsenicmethylation capacity. HighMMA%, low DMA% and AS3MT rs1046778 C/C + C/T genotype predicted a significantly higher risk of BC according to stepwisemultiple logistic regression analyses. AS3MT gene polymorphisms and arsenicmethylation capacity appeared to affect BC risk independently.

Original languageEnglish
Pages (from-to)328-338
Number of pages11
JournalToxicological Sciences
Volume164
Issue number1
DOIs
Publication statusPublished - Jul 1 2018

Fingerprint

Methylation
Methyltransferases
Arsenic
Polymorphism
Urinary Bladder Neoplasms
Genotype
Oxidation
Haplotypes
Dynamic mechanical analysis
Genes
Cacodylic Acid
Odds Ratio
Atomic absorption spectrometry
High performance liquid chromatography
Hydrides
Gold
Logistics
Spectrum Analysis
Logistic Models
High Pressure Liquid Chromatography

Keywords

  • Arsenic
  • Arsenic methylation
  • AS3MT
  • Bladder cancer
  • Polymorphism

ASJC Scopus subject areas

  • Toxicology

Cite this

Polymorphisms of arsenic (13 Oxidation State) methyltransferase and arsenic methylation capacity affect the risk of bladder cancer. / Lin, Ying Chin; Chen, Wei Jen; Huang, Chao Yuan; Shiue, Horng Sheng; Su, Chien Tien; Ao, Pui Lam; Pu, Yeong Shiau; Hsueh, Yu Mei.

In: Toxicological Sciences, Vol. 164, No. 1, 01.07.2018, p. 328-338.

Research output: Contribution to journalArticle

Lin, Ying Chin ; Chen, Wei Jen ; Huang, Chao Yuan ; Shiue, Horng Sheng ; Su, Chien Tien ; Ao, Pui Lam ; Pu, Yeong Shiau ; Hsueh, Yu Mei. / Polymorphisms of arsenic (13 Oxidation State) methyltransferase and arsenic methylation capacity affect the risk of bladder cancer. In: Toxicological Sciences. 2018 ; Vol. 164, No. 1. pp. 328-338.
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