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Title: Polymorphisms in cell cycle regulatory genes, urinary arsenic profile and urothelial carcinoma

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 percentagemore » (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.« less
Authors:
;  [1] ;  [2] ;  [3] ; ;  [4] ;  [5]
  1. Graduate Institute of Public Health, Taipei Medical University, Taipei, Taiwan (China)
  2. Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)
  3. Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China)
  4. Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan (China)
  5. Department of Public Health, School of Medicine, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei 110, Taiwan (China), E-mail: ymhsueh@tmu.edu.tw
Publication Date:
OSTI Identifier:
21144136
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 232; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2008.06.011; PII: S0041-008X(08)00266-4; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABSORPTION SPECTROSCOPY; ARSENIC; CARCINOGENESIS; CARCINOMAS; CELL CYCLE; DOSE-RESPONSE RELATIONSHIPS; ENZYME IMMUNOASSAY; GENES; GENOTYPE; HEALTH HAZARDS; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; HYDRIDES; MONOCLINIC LATTICES; POLYMERASE CHAIN REACTION; POLYMERASES; SENSITIVITY