Polymorphisms in cell cycle regulatory genes, urinary arsenic profile and urothelial carcinoma
Journal
Toxicology and Applied Pharmacology
Journal Volume
232
Journal Issue
2
Pages
203-209
Date Issued
2008
Author(s)
Abstract
Introduction: Polymorphisms in p53, p21 and CCND1 could regulate the progression of the cell cycle and might increase the susceptibility to inorganic arsenic-related cancer risk. The goal of our study was to evaluate the roles of cell cycle regulatory gene polymorphisms in the carcinogenesis of arsenic-related urothelial carcinoma (UC). Methods: A hospital-based case-controlled study was conducted to explore the relationships among the urinary arsenic profile, 8-hydroxydeoxyguanosine (8-OHdG) levels, p53 codon 72, p21 codon 31 and CCND1 G870A polymorphisms and UC risk. The urinary arsenic profile was determined using high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). 8-OHdG levels were measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP). Results: Subjects carrying the p21 Arg/Arg genotype had an increased UC risk (age and gender adjusted OR = 1.53; 95% CI, 1.02-2.29). However, there was no association of p53 or CCND1 polymorphisms with UC risk. Significant effects were observed in terms of a combination of the three gene polymorphisms and a cumulative exposure of cigarette smoking, along with the urinary arsenic profile on the UC risk. The higher total arsenic concentration, monomethylarsonic acid percentage (MMA%) and lower dimethylarsinic acid percentage (DMA%), possessed greater gene variant numbers, had a higher UC risk and revealed significant dose-response relationships. However, effects of urinary 8-OHdG levels combined with three gene polymorphisms did not seem to be important for UC risk. Conclusions: The results showed that the variant genotype of p21 might be a predictor of inorganic arsenic-related UC risk. ? 2008 Elsevier Inc. All rights reserved.
Subjects
8-hydroxydeoxyguanine; CCND1; Cell cycle; p21; p53; Polymorphism; Urinary arsenic profile; Urothelial carcinoma
SDGs
Other Subjects
8 hydroxydeoxyguanosine; adenine; arsenic; cacodylic acid; guanine; methanearsonic acid; adult; article; bladder carcinogenesis; bladder carcinoma; cancer risk; case control study; CCND1 gene; cell cycle; cell cycle regulation; cigarette smoking; confidence interval; controlled study; dose response; enzyme linked immunosorbent assay; female; gene; genetic polymorphism; genotype; high performance liquid chromatography; human; human tissue; hydride generator atomic absorption spectrometry; major clinical study; male; p21 gene; polymerase chain reaction; restriction fragment length polymorphism; risk assessment; risk factor; tumor suppressor gene; Arsenic; Carcinoma, Transitional Cell; Case-Control Studies; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Deoxyguanosine; Female; Genes, cdc; Humans; Male; Middle Aged; Polymorphism, Genetic; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms; Variation (Genetics)
Type
journal article