Abstract
The risk of urothelial carcinoma (UC) and urinary arsenic speciation have been evaluated in a few case–control studies; however, the association has not been verified in a prospective cohort study. The aim of this study was to examine the association between urinary arsenic speciation and the incidence of UC in a cohort study. A total of 1,078 residents of southwestern Taiwan were followed for an average of 12 years. A high-performance liquid chromatography/hydride generator and an atomic absorption spectrometry were used to measure urinary arsenite, arsenate, monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV). The incidence of UC was estimated by examining the National Cancer Registry of Taiwan between January 1985 and December 2001. There were 37 newly diagnosed cases of UC during a follow-up period of 11,655 person-years. Significantly higher percentages of MMAV and lower percentages of DMAV existed among the patients with UC than among the healthy residents. After adjustment for age, gender, educational level, and smoking status, the percentage of urinary DMAV was shown to have an inverse association with the risk of UC, having a relative risk (RR) of the tertile strata of 1.0, 0.3, and 0.3, respectively (p < 0.05 for the trend test). The RR (95% confidence interval) of residents with a cumulative arsenic exposure (CAE) of ≥20 mg/l-year and a higher percentage of MMAV or a CAE of ≥20 mg/l-year and a lower percentage of DMAV was 3.7 (1.2–11.6) or 4.2 (1.3–13.4) compared to residents with a CAE of <20 mg/l-year and a lower percentage of MMAV or a CAE of <20 mg/l-year and a higher percentage of DMAV respectively. There was a significant association between inefficient arsenic methylation and the development of UC in the residents in the high CAE exposure strata in an area of southwestern Taiwan endemic for arseniasis.
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Abbreviations
- UC:
-
Urothelial carcinoma
- % DMAV :
-
Percentage of DMAV
- %InAsV :
-
Percentage of InAs
- %MMAV :
-
Percentage of MMAV
- AsIII :
-
Arsenite
- AsV :
-
Arsenate
- InAs:
-
Inorganic arsenic
- BFD:
-
Blackfoot disease
- CAE:
-
Cumulative arsenic exposure
- DMAV :
-
Dimethylarsinic acid
- InAs:
-
Inorganic arsenic
- MMAV :
-
Monomethylarsonic acid
- PMI:
-
Primary methylation indices
- SIRs:
-
Standardized incidence ratios
- SMI:
-
Secondary methylation index
References
IARC (1980) Some metals and metallic compounds. International Agency for Research on Cancer, Lyon, Franch, p 325
Chen CJ, Chuang YC, Lin TM, Wu HY (1985) Malignant neoplasms among residents of a blackfoot disease-endemic area in Taiwan: high-arsenic artesian well water and cancers. Cancer Res 45:5895–5899
Chen CJ, Chen CW, Wu MM, Kuo TL (1992) Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. Br J Cancer 66:888–892
Chiou HY, Hsueh YM, Liaw KF et al (1995) Incidence of internal cancers and ingested inorganic arsenic: a seven-year follow-up study in Taiwan. Cancer Res 55:1296–1300
National Research Council (2001) Arsenic in drinking water: 2001 update. National Academy Press, Washington, DC
Tapio S, Grosche B (2006) Arsenic in the aetiology of cancer. Mutat Res -Rev Mutat Res 612:215–246
Smith AH, Goycolea M, Haque R, Biggs ML (1998) Marked increase in bladder and lung cancer mortality in a region of Northern Chile due to arsenic in drinking water. Am J Epidemiol 147:660–669
Marshall G, Ferreccio C, Yuan Y et al (2007) Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J Natl Cancer Inst 99:920–928
HopenhaynRich C, Biggs ML, Fuchs A et al (1996) Bladder cancer mortality associated with arsenic in drinking water in Argentina. Epidemiology 7:117–124
Vahter M (1981) Biotransformation of trivalent and pentavalent inorganic arsenic in mice and rats. Environ Res 25:286–293
Vahter M (2002) Mechanisms of arsenic biotransformation. Toxicology 181–182:211–217
Buchet JP, Lauwerys R, Roels H (1981) Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite, monomethylarsonate, or dimethylarsinate in man. Int Arch Occup Environ Health 48:71–79
Buchet JP, Lauwerys R, Roels H (1981) Urinary excretion of inorganic arsenic and its metabolites after repeated ingestion of sodium metaarsenite by volunteers. Int Arch Occup Environ Health 48:111–118
Vahter M (1999) Methylation of inorganic arsenic in different mammalian species and population groups. Sci Progr 82:69–88
Styblo M, Del Razo LM, Vega L et al (2000) Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells. Arch Toxicol 74:289–299
Petrick JS, Jagadish B, Mash EA, Aposhian HV (2001) Monomethylarsonous acid (MMA(III)) and arsenite: LD(50) in hamsters and in vitro inhibition of pyruvate dehydrogenase. Chem Res Toxicol 14:651–656
Nesnow S, Roop BC, Lambert G et al (2002) DNA damage induced by methylated trivalent arsenicals is mediated by reactive oxygen species. Chem Res Toxicol 15:1627–1634
Chen YC, Su HJ, Guo YL et al (2003) Arsenic methylation and bladder cancer risk in Taiwan. Cancer Causes Control 14:303–310
Chen YC, Guo YL, Su HJ et al (2003) Arsenic methylation and skin cancer risk in southwestern Taiwan. J Occup Environ Med 45:241–248
Hsueh YM, Chiou HY, Huang YL et al (1997) Serum beta-carotene level, arsenic methylation capability, and incidence of skin cancer. Cancer Epidemiol Biomarkers Prev 6:589–596
Yu RC, Hsu KH, Chen CJ, Froines JR (2000) Arsenic methylation capacity and skin cancer. Cancer Epidemiol Biomarkers Prev 9:1259–1262
Pu YS, Yang SM, Huang YK et al (2007) Urinary arsenic profile affects the risk of urothelial carcinoma even at low arsenic exposure. Toxicol Appl Pharmacol 218:99–106
Steinmaus C, Bates MN, Yuan Y et al (2006) Arsenic methylation and bladder cancer risk in case–control studies in Argentina and the United States. J Occup Environ Med 48:478–488
Steinmaus C, Yuan Y, Kalman D, Atallah R, Smith AH (2005) Intra individual variability in Arsenic methylation in a U.S. population. Cancer Epidemiol Biomarkers Prev 14:919–924
Hindmarsh JT (2002) Caveats in hair analysis in chronic arsenic poisoning. Clin Biochem 35:1–11
Hughes MF (2006) Biomarkers of exposure: a case study with inorganic arsenic. Environ Health Perspect 114:1790–1796
Wu HY, Chen KP, Tseng WP, Hsu CL (1961) Epidemiologic studies on blackfoot disease: I. Prevalence and incidence of the disease by age, sex, occupation and geographical distribution. Mem College Med Natl Taiwan Univ 7:33–50
Chen CJ, Hsueh YM, Lai MS et al (1995) Increased prevalence of hypertension and long-term arsenic exposure. Hypertension 25:53–60
Chen CJ, You SL, Lin LH, Hsu WL, Yang YW (2002) Cancer epidemiology and control in Taiwan: a brief review. Jpn J Clin Oncol 32:S66–S81
US Department of Health, Human Services (2001) International classification of diseases, ninth revision, clinical modification. US Public Health Service, Washington, DC
SEER Program NCI (2001) Conversion of morphology of ICD-O-2 to ICD-O-3. In: Percy C, Fritz A, Ries L (eds) National Cancer Institute, Bethedsa, pp 1–160
Hsueh YM, Huang YL, Huang CC et al (1998) Urinary levels of inorganic and organic arsenic metabolites among residents in an arseniasis-hyperendemic area in Taiwan. J Toxicol Environ Health A 54:431–444
Kuo TL (1964) Arsenic content of artesian well water in endemic area of chronic arsenic poisoning. Rep Inst Pathol Natl Taiwan Univ 20:7–13
Lo MC, Hsen YC, Lin BK (1977) Arsenic content of underground water in Taiwan: second report. Taiwan Provincial Institute of Environmental Sanitation, Taichung
Breslow NE, Day NE (1987) Statistical methods in cancer research. vol 2. The analysis of cohort studies. International Agency for Research on Cancer, Lyon, p 120
Steinmaus C, Yuan Y, Kalman D, Atallah R, Smith AH (2005) Intraindividual variability in arsenic methylation in a U.S. population. Cancer Epidemiol Biomarkers Prev 14:919–924
Hopenhayn-Rich C, Biggs ML, Smith AH, Kalman DA, Moore LE (1996) Methylation study of a population environmentally exposed to arsenic in drinking water. Environ Health Perspect 104:620–628
Hsueh YM, Hsu MK, Chiou HY, Yang MH, Huang CC, Chen CJ (2002) Urinary arsenic speciation in subjects with or without restriction from seafood dietary intake. Toxicol Lett 133:83–91
Concha G, Nermell B, Vahter MV (1998) Metabolism of inorganic arsenic in children with chronic high arsenic exposure in northern Argentina. Environ Health Perspect 106:355–359
Vahter M, Concha G, Nermell B, Nilsson R, Dulout F, Natarajan AT (1995) A unique metabolism of inorganic arsenic in native Andean women. Eur J Pharmacol 293:455–462
Chiou HY, Hsueh YM, Hsieh LL et al (1997) Arsenic methylation capacity, body retention, and null genotypes of glutathione S-transferase M1 and T1 among current arsenic-exposed residents in Taiwan. Mutat Res -Rev Mutat Res 386:197–207
Marnell LL, Garcia-Vargas GG, Chowdhury UK et al (2003) Polymorphisms in the human monomethylarsonic acid (MMA V) reductase/hGSTO1 gene and changes in urinary arsenic profiles. Chem Res Toxicol 16:1507–1513
Schmuck EM, Board PG, Whitbread AK et al (2005) Characterization of the monomethylarsonate reductase and dehydroascorbate reductase activities of Omega class glutathione transferase variants: implications for arsenic metabolism and the age-at-onset of Alzheimer’s and Parkinson’s diseases. Pharmacogenet Genomics 15:493–501
Wood TC, Salavaggione OE, Mukherjee B et al (2006) Human arsenic methyltransferase (AS3MT) pharmacogenetics: gene resequencing and functional genomics studies. J Biol Chem 281:7364–7373
Francesconi KA, Kuehnelt D (2004) Determination of arsenic species: a critical review of methods and applications, 2000–2003. Analyst 129:373–395
Thomas DJ, Styblo M, Lin S (2001) The cellular metabolism and systemic toxicity of arsenic. Toxicol Appl Pharmacol 176:127–144
Vega L, Styblo M, Patterson R, Cullen W, Wang C, Germolec D (2001) Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes. Toxicol Appl Pharmacol 172:225–232
Drobna Z, Jaspers I, Thomas DJ, Styblo M (2003) Differential activation of AP-1 in human bladder epithelial cells by inorganic and methylated arsenicals. FASEB J 17:67–69
Gong ZL, Lu XF, Cullen WR, Le XC (2001) Unstable trivalent arsenic metabolites, monomethylarsonous acid and dimethylarsinous acid. J Anal At Spectrum 16:1409–1413
Del Razo LM, Styblo M, Cullen WR, Thomas DJ (2001) Determination of trivalent methylated arsenicals in biological matrices. Toxicol Appl Pharmacol 174:282–293
Valenzuela OL, Borja-Aburto VH, Garcia-Vargas GG et al (2005) Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic. Environ Health Perspect 113:250–254
Le XC, Cullen WR, Reimer KJ (1994) Human urinary arsenic excretion after one-time ingestion of seaweed, crab, and shrimp. Clin Chem 40:617–624
Ma M, Le XC (1998) Effect of arsenosugar ingestion on urinary arsenic speciation. Clin Chem 44:539–550
Steinmaus C, Yuan Y, Kalman D, Atallah R, Smith AH (2005) Intraindividual variability in arsenic methylation in a U.S. population. Cancer Epidemiol Biomarkers Prev 14:919–924
Acknowledgments
The study was supported by grants (NSC-89-2320-B038-013, NSC-89-2314-B038-049, NSC-90-2320-B-038-021, NSC91-3112-B-038-0019, NSC92-2321-B-038-004, NSC92-3112-B-038-001, NSC93-2321-B-038-012, NSC93-3112-B-038-001, NSC94-2314-B-038-023, and NSC95-2314-B-038-007) from the National Science Council, Executive Yuan, ROC.
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Huang, YK., Huang, YL., Hsueh, YM. et al. Arsenic exposure, urinary arsenic speciation, and the incidence of urothelial carcinoma: a twelve-year follow-up study. Cancer Causes Control 19, 829–839 (2008). https://doi.org/10.1007/s10552-008-9146-5
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DOI: https://doi.org/10.1007/s10552-008-9146-5