title: Arsenic methylation and bladder cancer risk in Taiwan.
abstract: OBJECTIVE
  The mechanism of arsenic detoxification in humans remains unclear. Data are especially lacking for low-level arsenic exposure. We hypothesize that arsenic methylation ability, defined as the ratios of monomethylarsonic acid (MMA(V))/inorganic arsenic (primary arsenic methylation index, PMI) and dimethylarsinic acid (DMA(V))/ MMA(V) (secondary arsenic methylation index, SMI), may modify the association between cumulative arsenic exposure (CAE, mg/L-year) and the risk of bladder cancer. In this study we investigated the relationship among arsenic methylation ability, CAE, and the risk of bladder cancer in a hospital-based case-control study in southwestern Taiwan.
  
  
  METHODS
  From January 1996 to December 1999 we identified 49 patients with newly diagnosed cases of bladder cancer at the National Cheng-Kung University (NCKU) Medical Center; controls consisted of 224 fracture and cataract patients selected from the same medical center. The levels of four urinary arsenic species: arsenite (As(III)), arsenate (As(V)), MMA(V), and DMA(V)) were determined in all subjects by using the high-performance liquid chromatography hydride-generation atomic absorption spectrometry (HPLC-HGAAS). CAE was estimated by using published data collected in a survey from 1974 to 1976.
  
  
  RESULTS
  Compared to a CAE < or = 2 mg/L-year, CAE > 12 mg/L-year was associated with an increased risk of bladder cancer (multivariate odds ratio (OR) 4.23, 95% confidence interval (CI) 1.12-16.01), in the setting of a low SMI (< or = 4.8). Compared to women, smoking men (OR 6.23, 95% CI 1.88-20.62) and non-smoking men (OR 3.25, 95% CI 0.95-11.06) had higher risks of bladder cancer. Given the same level of PMI, smoking men (OR 9.80, 95% CI 2.40-40.10) and non-smoking men (OR 4.45, 95% CI 1.00-19.84) had a higher risk of bladder cancer when compared to women. With the same level of SMI, both smoking men (OR 6.28, 95% CI 1.76-22.39) and non-smoking men (OR 3.31, 95% CI 0.84-12.97) had a higher risk of bladder cancer when compared to women.
  
  
  CONCLUSIONS
  Subjects with low SMI have a substantially increased risk of bladder cancer, especially when combined with high CAE levels.
authors.affiliation: Occupational Health Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Yen-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Huey-Jen Jenny
authors.initials: HJ
authors.lastname: Su
authors.forename: Yu-Liang Leon
authors.initials: YL
authors.lastname: Guo
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Hsueh
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Smith
authors.forename: Louise M
authors.initials: LM
authors.lastname: Ryan
authors.forename: Meei-Shyuan
authors.initials: MS
authors.lastname: Lee
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000368:Aged; D001152:Arsenicals / Q000378:metabolism* / Q000652:urine; D002101:Cacodylic Acid / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced* / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking; D013624:Taiwan / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D014877:Water Pollution, Chemical; D014881:Water Supply
chemical_list: D001152:Arsenicals; D002101:Cacodylic Acid; C020300:monomethylarsonic acid