Cancer Causes & Control

, Volume 18, Issue 10, pp 1141–1151

Nitrate in public water supplies and the risk of renal cell carcinoma

  • Mary H. Ward
  • Jennifer A. Rusiecki
  • Charles F. Lynch
  • Kenneth P. Cantor
Original Paper


Drinking water and dietary sources of nitrate and nitrite can react in vivo with amines and amides to form N-nitroso compounds (NOC), potent animal carcinogens. Nitrate is a widespread contaminant of drinking water supplies especially in agricultural areas. We conducted a population-based case–control study of renal cell carcinoma in 1986–1989 in Iowa, a state with elevated levels in many public water supplies. We collected a lifetime water source history, but due to limited monitoring data, most analyses focused on the subpopulation, who used Iowa public supplies with nitrate measurements (actual or imputed data) for ≥70% of their person-years since 1960 (201 cases, 1,244 controls). We computed the average nitrate level and years using a public supply with nitrate levels >5 and >10 mg/l. Dietary nitrate and nitrite were estimated from a 55-item food frequency questionnaire. There was no association of renal cell carcinoma with the average nitrate level and years using public supplies >5 and >10 mg/l nitrate-nitrogen (10+ years >5 mg/l odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.66, 1.60). However, higher nitrate exposure was associated with an increased risk among subgroups with above the median red meat intake (10+ years >5 mg/l OR = 1.91, 95% CI 1.04–3.51) or below the median vitamin C intake (10+ years >5 mg/l OR = 1.90, 95% CI 1.01, 3.56), dietary factors that increase the endogenous formation of NOC. Exclusion of long-term Des Moines residents, a large proportion of the high exposure categories, attenuated the association. These findings deserve additional study in populations with high water nitrate intake and information on dietary intakes.


Renal cell carcinoma Drinking water Nitrate Nitrite N-nitroso compounds Diet 


  1. 1.
    Chow WH, Devesa SS, Warren JL et al (1999) The rising incidence of renal cell carcinoma in the United States. JAMA 281:1628–1631PubMedCrossRefGoogle Scholar
  2. 2.
    Ries LAG, Eisner MP, Kosary CL et al (eds) (2005) SEER cancer statistics review, 1975–2002. National Cancer Institute: Bethesda, MD,, based on November 2004 SEER data submission, posted to the SEER web site 2005
  3. 3.
    Moore LE, Wilson RT, Campleman SL (2005) Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk: a review. Cancer Invest 23:240–255PubMedCrossRefGoogle Scholar
  4. 4.
    Spalding RF, Exner ME (1993) Occurrence of nitrate in groundwater—a review. J Environ Qual 22:392–402CrossRefGoogle Scholar
  5. 5.
    Fields S (2004) Global nitrogen: cycling out of control. Environ Health Persp 112:A557–A563Google Scholar
  6. 6.
    Ward MH, deKok TM, Levallois P et al (2005) Drinking water nitrate and health: recent findings and research needs. Environ Health Perspect 113:1607–1614PubMedCrossRefGoogle Scholar
  7. 7.
    Bogovski P, Bogovski S (1981) Animal species in which N-nitroso compounds induce cancer. Int J Cancer 27:471–474PubMedCrossRefGoogle Scholar
  8. 8.
    Hard GC (1998) Mechanisms of chemically induced renal carcinogenesis in the laboratory rodent. Toxicol Pathol 26:104–112PubMedCrossRefGoogle Scholar
  9. 9.
    Tricker AR (1997) N-nitroso compounds and man: sources of exposure, endogenous formation and occurrence in body fluids. Eur J Cancer Prev 6:226–268PubMedCrossRefGoogle Scholar
  10. 10.
    Bartsch H, Ohshima H, Pignatelli B (1988) Inhibitors of endogenous nitrosation. Mechanisms and implications in human cancer prevention. Mutat Res 202:307–324PubMedGoogle Scholar
  11. 11.
    Gulis G, Czompolyova M, Cerhan JR (2002) An ecologic study of nitrate in municipal drinking water and cancer incidence in Trnava district, Slovakia. Environ Res 88:182–187PubMedCrossRefGoogle Scholar
  12. 12.
    Volkmer BG, Ernst B, Simon J et al (2005) Influence of nitrate levels in drinking water on urological malignancies: a community-based cohort study. BJU Int 95:972–976PubMedCrossRefGoogle Scholar
  13. 13.
    Weyer PJ, Cerhan JR, Kross BC et al (2001) Municipal drinking water nitrate level and cancer risk in older women: the Iowa Women’s Health Study. Epidemiology 12:327–338PubMedCrossRefGoogle Scholar
  14. 14.
    Parker AS, Cerhan JR, Lynch CF, Ershow AG, Cantor KP (2002) Gender, alcohol consumption, and renal cell carcinoma. Am J Epidemiol 155:455–462PubMedCrossRefGoogle Scholar
  15. 15.
    Parker AS, Cerhan JR, Lynch CF, Leibovich BC, Cantor KP (2004) History of urinary tract infection and risk of renal cell carcinoma. Am J Epidemiol 159:42–48PubMedCrossRefGoogle Scholar
  16. 16.
    Zhang Y, Cantor KP, Lynch CF, Zheng T (2004) A population-based case–control study of occupation and renal cell carcinoma risk in Iowa. J Occup Environ Med 46:235–240PubMedCrossRefGoogle Scholar
  17. 17.
    Ward MH, Cantor KP, Riley D, Merkle S, Lynch CF (2003) Nitrate in public water supplies and risk of bladder cancer. Epidemiology 14:183–190PubMedCrossRefGoogle Scholar
  18. 18.
    DeRoos AJ, Ward MH, Lynch CF, Cantor KP (2003) Nitrate in public water systems and the risk of colon and rectum cancers. Epidemiology 14:640–649CrossRefGoogle Scholar
  19. 19.
    Center for Health Effects of Environmental Contaminants. Nitrate fact sheet. (last accessed 3 October, 2006)
  20. 20.
    Kross BC, Hallberg GR, Bruner DR, Cherryholmes K, Johnson JK (1993) The nitrate contamination of private well water in Iowa. Am J Public Health 83:270–272PubMedCrossRefGoogle Scholar
  21. 21.
    National Academy of Sciences (1981) The health effects of nitrate, nitrite, and N-nitroso compounds. National Academy Press, Washington DCGoogle Scholar
  22. 22.
    White JW (1975) Relative significance of dietary sources of nitrate and nitrite. J Agric Food Chem 23:886–891PubMedCrossRefGoogle Scholar
  23. 23.
    Panalaks T, Iyengar JR, Sen NP (1973) Nitrate, nitrite, and dimethylnitrosamine in cured meat products. J A O A C 56:621–625Google Scholar
  24. 24.
    Panalaks T, Iyengar JR, Donaldson BA, Miles WF, Sen NP (1974) Further survey of cured meat products for volatile N-nitrosamines. J A O A C 57:806–812Google Scholar
  25. 25.
    Dresser CM (1983) From nutrient data to a database for health and nutrition examination survey: organization, coding, and values—real or imputed. In: Proceedings of the Eighth National Nutrient Data Base Conference, Minneapolis, MNGoogle Scholar
  26. 26.
    Chilvers C, Inskip H, Caygill C, Bartholomew B, Fraser P, Hill M (1984) A survey of dietary nitrate in well-water users. Int J Epidemiol 13:324–331PubMedCrossRefGoogle Scholar
  27. 27.
    Mirvish SS, Grandjean AC, Moller H et al (1992) N-Nitrosoproline excretion by rural Nebraskans drinking water of varied nitrate content. Cancer Epidemiol Biomarkers Prev 1:455–461PubMedGoogle Scholar
  28. 28.
    Mirvish SS (1994) Experimental evidence for inhibition of N-nitroso compound formation as a factor in the negative correlation between vitamin C consumption and the incidence of certain cancers. Cancer Res 54:1948s–1951sPubMedGoogle Scholar
  29. 29.
    Vermeer I, Pachen DM, Dallinga JW, Kleinjans JC, van Maanen JM (1998) Volatile N-nitrosamine formation after intake of nitrate at the ADI level in combination with an amine-rich diet. Environ Health Perspect 106:459–463PubMedCrossRefGoogle Scholar
  30. 30.
    Cross AJ, Pollock JR, Bingham SA (2003) Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat. Cancer Res 63:2358–2360PubMedGoogle Scholar
  31. 31.
    Moller H, Landt J, Perdersen E, Jensen P, Autrup H, Jensen O (1989) Endogenous nitrsation in relation to nitrate exposure from drinking water and diet in a Danish rural population. Cancer Res 49:3117–3121PubMedGoogle Scholar
  32. 32.
    Wolk A, Lindblad P, Adami H (1996) Nutrition and renal cell cancer. Cancer Causes Control 7:5–18PubMedCrossRefGoogle Scholar
  33. 33.
    Rashidkhani B, Lindblad P, Wolk A (2005) Fruits, vegetables and risk of renal cell carcinoma: a prospective study of Swedish women. Int J Cancer 113:451–455PubMedCrossRefGoogle Scholar
  34. 34.
    Hu J, Mao Y, White K, The Canadian Cancer Registries Epidemiology Research Group (2003) Diet and vitamin or mineral supplement and risk of renal cell carcinoma in Canada. Cancer Causes Control 14:705–714PubMedCrossRefGoogle Scholar
  35. 35.
    Handa K, Kreiger N (2002) Diet patterns and the risk of renal cell carcinoma. Public Health Nutr 5:757–767PubMedCrossRefGoogle Scholar
  36. 36.
    Yuan J-M, Gago-Dominquez M, Castelao E, Hankin JH, Ross Rk, Yu MC (1998) Cruciferous vegetables in relation to renal cell carcinoma. Int J Cancer 77:211–216PubMedCrossRefGoogle Scholar
  37. 37.
    McLaughlin JK, Gao YT, Gao RN et al (1992) Risk factors for renal cell cancer in Shanghai, China. Int J Cancer 52:562–565PubMedCrossRefGoogle Scholar
  38. 38.
    MacClure M, Willett W (1990) A case–control study of diet and risk of renal adenocarcinoma. Epidemiology 1:430–440CrossRefGoogle Scholar
  39. 39.
    Lindblad P, Wolk A, Bergstrom R, Adami H (1997) Diet and risk of renal cell cancer: a population-based case–control study. Cancer Epidemiol Biomarkers Prev 6:215–225PubMedGoogle Scholar
  40. 40.
    van Dijk BAC, Schouten LJ, Lambertus ALM, Klemeney R, Goldbohm A, van den Brandt PA (2005) Vegetable and fruit consumption and risk of renal cell carcinoma: results from The Netherlands cohort study. Int J Cancer 117:648–654PubMedCrossRefGoogle Scholar
  41. 41.
    Mellemgaard A, McLaughlin JK, Overvad K, Olsen JH (1996) Dietary risk factors for renal cell carcinoma in Denmark. Eur J Cancer 32A:673–682PubMedCrossRefGoogle Scholar
  42. 42.
    Chow W, Gridley G, McLauglin JK et al (1994) Protein intake and risk of renal cell cancer. JNCI 86:1131–1139PubMedCrossRefGoogle Scholar
  43. 43.
    Wolk A, Gridley G, Niwa S et al (1996) International renal cell cancer study. VII. Role of diet. Int J Cancer 65:67–73PubMedCrossRefGoogle Scholar
  44. 44.
    Cantor KP, Lynch CF, Hildesheim ME et al (1998) Drinking water source and chlorination by-products. I. Risk of bladder cancer. Epidemiology 9:21–28PubMedCrossRefGoogle Scholar
  45. 45.
    Nolan BT, Hitt KJ, Ruddy BC (2002) Probability of nitrate contamination of recently recharged groundwaters in the conterminous United States. Environ Sci Technol 36:2138–2145PubMedCrossRefGoogle Scholar
  46. 46.
    Furukawa F, Nishikawa A, Ishiwata H, Takahashi M, Hayashi Y, Hirose M (2000) Renal carcinogenicity of concurrently administered fish meal and sodium nitrite in F344 rats. Jpn J Cancer Res 91:139–147PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media B.V. 2007

Authors and Affiliations

  • Mary H. Ward
    • 1
  • Jennifer A. Rusiecki
    • 2
  • Charles F. Lynch
    • 3
  • Kenneth P. Cantor
    • 1
  1. 1.Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology BranchNational Cancer Institute, NIH/DHHSBethesdaUSA
  2. 2.Department of Preventive Medicine and BiometricsUniformed Services University of the Health SciencesBethesdaUSA
  3. 3.Department of EpidemiologyUniversity of IowaIowa CityUSA

Personalised recommendations