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Polymorphisms of human 8-oxoguanine DNA glycosylase 1 and 8-hydroxydeoxyguanosine increase susceptibility to arsenic methylation capacity-related urothelial carcinoma.
- Source :
-
Archives of toxicology [Arch Toxicol] 2016 Aug; Vol. 90 (8), pp. 1917-27. Date of Electronic Publication: 2015 Sep 10. - Publication Year :
- 2016
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Abstract
- Arsenic causes oxidative stress in cultured animal and human cells, and it is a well-documented human carcinogen. We conducted a hospital-based case-control study including 167 cases of urothelial carcinoma (UC) and 334 age- and gender-matched healthy controls to evaluate the relationships between urinary arsenic profiles, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels, and human 8-oxoguanine DNA glycosylase (hOGG1) genotypes and UC. The urinary arsenic species were analyzed by high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Genotyping for hOGG1 (Ser326Cys) and hOGG1 (-15C>G) was performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Urinary 8-OHdG was measured with high-sensitivity enzyme-linked immunosorbent assay kits. The results indicated that the hOGG1 326 Cys/Cys genotype and the hOGG1 -15C>G G/G genotype were associated with an increased risk of UC (OR [95 % CI] 1.57 [1.04-2.35] and 1.57 [1.04-2.35], respectively). Participants with high urinary total arsenic, regardless of the haplotype of hOGG1 Ser326Cys and the -15C>G polymorphism, had significantly higher urinary 8-OHdG compared to participants with low urinary total arsenic. This is the first study to investigate the joint effects of high urinary total arsenic or inefficient arsenic methylation capacity indices, and the high-risk G-G haplotype of hOGG1 on the risk of UC. The findings are especially meaningful for participants with risk factors such as high urinary total arsenic, inefficient arsenic methylation indices, high urinary 8-OHdG, and the high-risk G-G haplotype of hOGG1 which are all associated with an increased UC risk.
- Subjects :
- 8-Hydroxy-2'-Deoxyguanosine
Arsenic urine
Carcinogens, Environmental metabolism
Carcinoma genetics
Carcinoma urine
Case-Control Studies
Data Interpretation, Statistical
Deoxyguanosine urine
Genetic Predisposition to Disease
Genotype
Humans
Methylation
Risk Factors
Urologic Neoplasms genetics
Urologic Neoplasms urine
Arsenic toxicity
Carcinogens, Environmental toxicity
Carcinoma chemically induced
DNA Glycosylases genetics
Deoxyguanosine analogs & derivatives
Polymorphism, Single Nucleotide
Urologic Neoplasms chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0738
- Volume :
- 90
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Archives of toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 26359225
- Full Text :
- https://doi.org/10.1007/s00204-015-1590-x