Comparison of arsenic methylation capacity and polymorphisms of arsenic methylation genes between bladder cancer and upper tract urothelial carcinoma
Journal
Toxicology Letters
Journal Volume
295
Pages
64-73
Date Issued
2018
Author(s)
Abstract
Arsenic exposure is an environmental risk factor for urothelial carcinoma (UC). The natural history of upper tract urothelial carcinoma (UTUC) differs from that of bladder cancer (BC). However, the risk factors of BC and UTUC are not exactly the same and should be discussed separately. The aims of this study were to evaluate 1) the association between arsenic methylation capacity and UTUC and/or BC, separately, and 2) the association between polymorphisms of the arsenic metabolism-related genes AS3MT, GSTOs, and PNP against BC and/or UTUC, separately. We conducted a hospital-based study and collected 216 BC and 212 UTUC cases, and 813 healthy controls, from September 2007 to October 2011. Urinary arsenic profiles were measured using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were identified using the Sequenom MassARRAY platform with iPLEX Gold chemistry. We found that inefficient arsenic methylation capacity was associated with BC in a significant dose-response relationship, but only found that high urinary total arsenic concentration was related to the risk of UTUC, also in a significant dose-response manner. Those with a total urinary arsenic level of > 30.28 μg/L compared to ? 9.78 μg/L, had a odds ratio (OR), and 95% confidence interval (CI) of UTUC, of 4.80 (2.22–10.39). The polymorphisms of AS3MT rs11191438, AS3MT rs10748835, and AS3MT rs1046778 were related to the risk of BC and UTUC, while the polymorphisms of AS3MT rs3740393, AS3MT rs11191453, and AS3MT rs11191454 were associated with arsenic methylation capacity. The AS3MT gene polymorphisms and arsenic methylation capacity appear to independently affect the risk of BC and UTUC. ? 2018 Elsevier B.V.
Other Subjects
arsenic; arsenic methyltransferase; genomic DNA; glutathione transferase; glutathione transferase omega; methyltransferase; purine nucleoside phosphorylase; s adenosylmethionine; unclassified drug; AS3MT protein, human; glutathione transferase; methyltransferase; organoarsenic derivative; purine nucleoside phosphorylase; adult; Article; bladder cancer; cancer risk; controlled study; DNA methylation; female; genotype; human; liquid chromatography; major clinical study; male; middle aged; priority journal; single nucleotide polymorphism; transitional cell carcinoma; urine sampling; atomic absorption spectrometry; bladder tumor; carcinoma; case control study; chemically induced; chi square distribution; comparative study; dose response; drug effect; enzymology; gene expression regulation; gene frequency; genetics; high performance liquid chromatography; metabolism; methylation; multiplex polymerase chain reaction; multivariate analysis; odds ratio; pathology; risk assessment; statistical model; urinary tract tumor; urine; urothelium; Arsenicals; Carcinoma; Case-Control Studies; Chi-Square Distribution; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gene Frequency; Glutathione Transferase; Humans; Logistic Models; Male; Methylation; Methyltransferases; Middle Aged; Multiplex Polymerase Chain Reaction; Multivariate Analysis; Odds Ratio; Polymorphism, Single Nucleotide; Purine-Nucleoside Phosphorylase; Risk Assessment; Spectrophotometry, Atomic; Urinary Bladder Neoplasms; Urologic Neoplasms; Urothelium
Publisher
Elsevier Ireland Ltd
Type
journal article