Cancer Causes & Control

, Volume 15, Issue 5, pp 465–472 | Cite as

Incidence of Transitional Cell Carcinoma of the Bladder and Arsenic Exposure in New Hampshire

  • Margaret R. Karagas
  • Tor D. Tosteson
  • J. Steven Morris
  • Eugene Demidenko
  • Leila A. Mott
  • John Heaney
  • Alan Schned


Objective: Arsenic is a known bladder carcinogen and populations exposed to high arsenic levels in their water supply have reported elevated bladder cancer mortality and incidence rates. To examine the effects of lower levels of arsenic exposure on bladder cancer incidence, we conducted a case–control study in New Hampshire, USA where levels above 10 μ/l are commonly found in private wells.

Methods: We studied 383 cases of transitional cell carcinoma of the bladder cancer, newly diagnosed between July 1, 1994 and June 30, 1998 and 641 general population controls. Individual exposure to arsenic was determined in toenail clippings using instrumental neutron activation analysis.

Results: Among smokers, an elevated odds ratio (OR) for bladder cancer was observed for the uppermost category of arsenic (OR: 2.17, 95% CI: 0.92–5.11 for greater than 0.330 mcg/g compared to less than 0.06 μ/g). Among never smokers, there was no association between arsenic and bladder cancer risk.

Conclusions: These, and other data, suggest that ingestion of low to moderate arsenic levels may affect bladder cancer incidence, and that cigarette smoking may act as a co-carcinogen.

arsenic bladder cancer case–control study drinking water epidemiologic study 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hopenhayn-Rich C, Biggs ML, Fuchs A, et al. (1996) Bladder cancer mortality associated with arsenic in drinking water in Argentina. Epidemiology 7: 117–124.PubMedGoogle Scholar
  2. 2.
    Chen CJ, Kuo TL, Wu MM (1988) Arsenic and cancers. Lancet 1: 414–415.CrossRefGoogle Scholar
  3. 3.
    Rivara MI, Cebrian M, Corey G, Hernandez M, Romieu I (1997) Cancer risk in an arsenic-contaminated area of Chile. Toxicol Ind Health 13: 321–338.PubMedGoogle Scholar
  4. 4.
    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.PubMedGoogle Scholar
  5. 5.
    Tsuda T, Babazono A, Yamamoto E, et al. (1995) Ingested arsenic and internal cancer: a historical cohort study followed for 33 years. Am J Epidemiol 141: 198–209.PubMedGoogle Scholar
  6. 6.
    Cuzick J, Sasieni P, Evans S (1992) Ingested arsenic, keratoses, and bladder cancer. Am J Epidemiol 136: 417–421.PubMedGoogle Scholar
  7. 7.
    Bates MN, Smith AH, Cantor KP (1995) Case-control study of bladder cancer and arsenic in drinking water. Am J Epidemiol 141: 523–530.PubMedGoogle Scholar
  8. 8.
    Kurttio P, Pukkala E, Kahelin H, Auvinen A, Pekkanen J (1999) Arsenic concentrations in well water and risk of bladder and kidney cancer in Finland. Environ Health Perspect 107: 705–710.PubMedGoogle Scholar
  9. 9.
    Chiou HY, Chiou ST, Hsu YH, et al. (2001) Incidence of transitional cell carcinoma and arsenic in drinking water: a follow-up study of 8, 102 residents in an arseniasis-endemic area in northeastern Taiwan [comment]. Am J Epidemiol 153: 411–418.CrossRefPubMedGoogle Scholar
  10. 10.
    Karagas MR, Tosteson TD, Blum J, et al. (1998) Design of an epidemiologic study of drinking water Arsenic exposure and skin and bladder cancer risk in a US population. Environ Health Perspect 106: 1047–1050.PubMedGoogle Scholar
  11. 11.
    Morris Brown L, Hoar Zahm S, Hoover RN, Fraumeni JF (1995) High bladder cancer mortality in rural New England (United States): an etiologic study. Cancer Causes Control 6: 361–368.PubMedGoogle Scholar
  12. 12.
    Karagas MR, Stukel TA, Tosteson TD (2002) Assessment of cancer risk and environmental levels of arsenic in New Hampshire. Int J Hyg Environ Health 205: 85–94.PubMedGoogle Scholar
  13. 13.
    Karagas MR, Stukel TA, Morris JS, et al. (2001) Skin cancer risk in relation to toenail arsenic concentrations in a US populationbased case-control study. Am J Epidemiol 153: 559–565.CrossRefPubMedGoogle Scholar
  14. 14.
    Newcomb PA, Longnecker MP, Storer BE, et al. (1996) Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women. Am J Epidemiol 142: 788–795.Google Scholar
  15. 15.
    Karagas MR, Tosteson TD, Blum J, et al. (2000) Measurement of low levels of arsenic exposure: a comparison of water and toenail concentrations. Am J Epidemiol 152: 84–90.CrossRefPubMedGoogle Scholar
  16. 16.
    Nichols TA, Morris JS, Mason MM, et al. (1998) The study of human nails as an intake monitor for arsenic using neutron activation analysis. J Radioanal Nucl Chem 236: 51–56.Google Scholar
  17. 17.
    Altman NS (1992) An introduction to kernal and nearest-neighbor nonparametric regression. Am Stat 46: 175–185.Google Scholar
  18. 18.
    Breslow NE, Day NE (1980) Statistical Methods in Cancer Research. Volume 1-The Analysis of Case-control Studies Lyon: IARC.Google Scholar
  19. 19.
    Pastor R, Guallar E (1998) Use of two-segmented logistic regression to estimate change-points in epidemiologic studies. Am J Epidemiol 148: 631–642.PubMedGoogle Scholar
  20. 20.
    Tsai S-M, Wang T-N, Ko Y-C (1999) Mortality for certain diseases in areas with high levels of arsenic in drinking water. Arch Environ Health 54: 186–193.PubMedGoogle Scholar
  21. 21.
    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.PubMedGoogle Scholar
  22. 22.
    Chen CJ, Wang CJ (1990) Ecological correlation between arsenic level in well water and age-adjusted mortality from malignant neoplasms. Cancer Res 50: 5470–5474.PubMedGoogle Scholar
  23. 23.
    Wu MM, Kuo TL, Hwang YH, Chen CJ (1989) Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. Am J Epidemiol 130: 1123-1132.Google Scholar
  24. 24.
    Chiang HS, Guo HR, Hong CL, Lin SM, Lee EF (1993) The incidence of bladder cancer in the black foot endemic area in Taiwan. Br J Cancer 71: 272–278.Google Scholar
  25. 25.
    Guo HR, Chiang HS, Hu H, Lipsitz SR, Monson RR (1997) Arsenic in drinking water and incidence of urinary cancers. Epidemiology 8: 545–550.CrossRefPubMedGoogle Scholar
  26. 26.
    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.PubMedGoogle Scholar
  27. 27.
    Chen CJ, Chuang YC, You SL, Lin TM, Wu HY (1986) A retrospective study on malignant neoplasms of bladder, lung and liver in blackfoot disease endemic area in Taiwan. Br J Cancer 53: 399–405.PubMedGoogle Scholar
  28. 28.
    Lewis DR, Southwick JW, Ouellet-Hellstrom R, Rench J, Calderon RL (1999) Drinking water arsenic in Utah: a cohort mortality study [comment]. Environ Health Perspect 107: 359–365PubMedGoogle Scholar
  29. 29.
    Tosteson T, Karagas M (2000) Designing an arsenic bladder cancer case-control study: what sample size is needed to detect the beginning of a dose response? In: Centeno J, Collery P, Vernet G, Finnkelman R, Gibb H, Etienne J, eds., Metal Ions in Biology and Medicine, Vol. 6, Paris: John Libbey and Company Ltd., pp. 28–30.Google Scholar
  30. 30.
    Wiencke JK, Yager JW, Varkonyi A, Hultner M, Lutze LH (1997) Study of arsenic mutagenesis using the plasmid shuttle vector pZ189 propagated in DNA repair proficient human cells. Mutat Res 386: 335–344.CrossRefPubMedGoogle Scholar
  31. 31.
    Tran HP, Prakash AS, Barnard R, Chiswell B, Ng JC (2002) Arsenic inhibits the repair of DNA damage induced by benzo(a)pyrene. Toxicol Lett 133: 59–67.CrossRefPubMedGoogle Scholar
  32. 32.
    Li JM, Rossman TG (1989) Inhibition of DNA ligase activity by arsenite: a possible mechanism of its comutagenesis. Mol Toxicol 2: 1–9.PubMedGoogle Scholar
  33. 33.
    Yager JW, Wiencke JK (1997) Inhibition of poly(ADP-ribose) polymerase by arsenite. Mutat Res 386: 345–351.CrossRefPubMedGoogle Scholar
  34. 34.
    Andrew AS, Karagas MR, Schned A, et al. (2003) Decreased expression of DNA repair genes ERCC1, XPF, and XPB, but not XPG or XPA among individuals exposed to arsenic in drinking water. Int J Cancer 104: 263–268.CrossRefPubMedGoogle Scholar
  35. 35.
    Zakharyan RA, Sampayo-Reyes A, Healy SM, et al. (2001) Human monomethylarsonic acid (MMA(V)) reductase is a member of the glutathione-S-transferase superfamily. Chem Res Toxicol 14: 1051–1057.CrossRefPubMedGoogle Scholar
  36. 36.
    Vahter M (2000) Genetic polymorphism in the biotransformation of inorganic arsenic and its role intoxicity. Toxicol Lett 112-113: 207–217.CrossRefGoogle Scholar
  37. 37.
    Chen Y-C, Su H-JJ, Guo Y-LL, et al. (2003) Arsenic methylation and bladder cancer risk in Taiwan. Cancer Causes Control 14: 303–310.CrossRefPubMedGoogle Scholar
  38. 38.
    Garland M, Morris JS, Rosner BA, et al. (1993) Toenail trace element levels as biomarkers: reproducibility over a 6-year period [published erratum appears in Cancer Epidemiol Biomarkers Prev 1994 Sep; 3(6): 523]. Cancer Epidemiol Biomarkers Prev 2: 493–497.PubMedGoogle Scholar
  39. 39.
    Karagas MR, Le XC, Morris S, et al. (2001) Markers of low level arsenic exposure for evaluating human cancer risk in a US population. Int J Occup Environ Health 14: 171–175.Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Margaret R. Karagas
    • 1
    • 2
  • Tor D. Tosteson
    • 1
  • J. Steven Morris
    • 3
  • Eugene Demidenko
    • 1
  • Leila A. Mott
    • 1
  • John Heaney
    • 4
  • Alan Schned
    • 5
  1. 1.Department of Community and Family Medicine and the Norris Cotton Cancer CenterDartmouth Medical SchoolLebanon
  2. 2.Section of Biostatistics and EpidemiologyDartmouth Medical SchoolLebanonUSA
  3. 3.Research Reactor CenterUniversity of MissouriColumbia
  4. 4.Department of SurgeryDartmouth Medical SchoolLebanon
  5. 5.Department of PathologyDartmouth Medical SchoolLebanon

Personalised recommendations