https://scholars.lib.ntu.edu.tw/handle/123456789/544466
Title: | Polymorphisms in cell cycle regulatory genes, urinary arsenic profile and urothelial carcinoma | Authors: | Chung C.-J. Huang C.-J. YEONG-SHIAU PU Su C.-T. Huang Y.-K. Chen Y.-T. Hsueh Y.-M. |
Keywords: | 8-hydroxydeoxyguanine; CCND1; Cell cycle; p21; p53; Polymorphism; Urinary arsenic profile; Urothelial carcinoma | Issue Date: | 2008 | Journal Volume: | 232 | Journal Issue: | 2 | Start page/Pages: | 203-209 | Source: | Toxicology and Applied Pharmacology | 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-52049091455&doi=10.1016%2fj.taap.2008.06.011&partnerID=40&md5=5041ccc5ccaed0af70ddbbe155a211ed https://scholars.lib.ntu.edu.tw/handle/123456789/544466 |
ISSN: | 0041-008X | DOI: | 10.1016/j.taap.2008.06.011 | SDG/Keyword: | 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) |
Appears in Collections: | 醫學系 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.