Polymorphisms of arsenic (13 Oxidation State) methyltransferase and arsenic methylation capacity affect the risk of bladder cancer
Journal
Toxicological Sciences
Journal Volume
164
Journal Issue
1
Pages
328-338
Date Issued
2018
Author(s)
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. ? The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
SDGs
Other Subjects
arsenic derivative; cacodylic acid; creatinine; methanearsonic acid; methyltransferase; arsenic; AS3MT protein, human; methyltransferase; adult; Article; atomic absorption spectrometry; bladder cancer; cancer risk; cigarette smoking; controlled study; creatinine urine level; female; genetic association; genetic risk; haplotype; high performance liquid chromatography; human; major clinical study; male; middle aged; oxidation; single nucleotide polymorphism; bladder tumor; case control study; enzymology; genetic predisposition; genetics; metabolism; methylation; risk; social aspects and related phenomena; statistical model; urine; Arsenic; Case-Control Studies; Female; Genetic Predisposition to Disease; Haplotypes; Humans; Logistic Models; Male; Methylation; Methyltransferases; Middle Aged; Polymorphism, Single Nucleotide; Risk; Sociological Factors; Urinary Bladder Neoplasms
Publisher
Oxford University Press
Type
journal article