Risk of Non-Hodgkin Lymphoma and Nitrate and Nitrite From Drinking Water and Diet

Introduction: Nitrate and nitrite are precursors in the in vivo formation of N-nitroso compounds, potent animal carcinogens. Methods: We conducted a population-based case–control study of non-Hodgkin lymphoma (NHL) in 1998 to 2000 in Iowa, Detroit, Seattle, and Los Angeles. Because nitrate levels were elevated in many drinking water supplies in Iowa, but not in the other study centers, we evaluated water nitrate levels and risk of NHL in Iowa only. Monitoring data for public supplies were linked to water source histories from 1960 onward. Nitrate was measured at interview homes with private wells. We limited most analyses to those with nitrate estimates for >70% of their person-years since 1960 (181 cases, 142 controls). For those in the diet arm of the study (458 cases, 383 controls from 4 centers) and for Iowa participants in both the diet and drinking water analyses, we estimated dietary nitrate and nitrite intake using a 117-item food-frequency questionnaire that included foods high in nitrate and nitrite. Odds ratios and 95% confidence intervals were calculated using logistic regression, adjusting for the study matching factors, education, and caloric intake (diet analyses only). Results: We found no overall association with the highest quartile of average drinking water nitrate (>2.90 mg/L nitrate-N: odds ratios = 1.2; 95% confidence interval = 0.6–2.2) or with years ≥5 mg/L (10+ years: 1.4; 0.7–2.9). We observed no evidence of an interaction between drinking water nitrate exposure and either vitamin C or red meat intake, an inhibitor and precursor, respectively, of N-nitroso compound formation. Among those in the diet arm, dietary nitrate was inversely associated with risk of NHL (highest quartile: 0.54; 0.34–0.86). Dietary nitrite intake was associated with increasing risk (highest quartile: 3.1; 1.7–5.5) largely due to intakes of bread and cereal sources of nitrite. Conclusion: Average drinking water nitrate levels below 3 mg/L were not associated with NHL risk. Our study had limited power to evaluate higher levels that deserve further study.

[1]  R. Sinha,et al.  Meat and meat-mutagen intake and risk of non-Hodgkin lymphoma: results from a NCI-SEER case-control study. , 2006, Carcinogenesis.

[2]  P. Hartge,et al.  Dietary determinants of one-carbon metabolism and the risk of non-Hodgkin's lymphoma: NCI-SEER case-control study, 1998-2000. , 2005, American journal of epidemiology.

[3]  G. Gulis,et al.  Workgroup Report: Drinking-Water Nitrate and Health—Recent Findings and Research Needs , 2005, Environmental health perspectives.

[4]  D. Weisenburger,et al.  Dietary factors and non-Hodgkin's lymphoma in Nebraska (United States) , 1994, Cancer Causes & Control.

[5]  H. Boeing.  Epidemiological research in stomach cancer: progress over the last ten years , 2005, Journal of Cancer Research and Clinical Oncology.

[6]  J. Cerhan,et al.  Risk of non-Hodgkin's lymphoma and family history of lymphatic, hematologic, and other cancers. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[7]  S. Fields.  Global Nitrogen: Cycling out of Control , 2004, Environmental health perspectives.

[8]  M. Ward,et al.  Nitrate in community water supplies and incidence of non-Hodgkin’s lymphoma in Sardinia, Italy , 2003, Journal of epidemiology and community health.

[9]  C. Lynch,et al.  Nitrate in Public Water Supplies and Risk of Bladder Cancer , 2003, Epidemiology.

[10]  J. Cerhan,et al.  An ecologic study of nitrate in municipal drinking water and cancer incidence in Trnava District, Slovakia. , 2002, Environmental research.

[11]  J. Cerhan,et al.  Municipal Drinking Water Nitrate Level and Cancer Risk in Older Women: The Iowa Women’s Health Study , 2001, Epidemiology.

[12]  K. Helzlsouer,et al.  A Case-Control Study of Nitrate in Drinking Water and Non-Hodgkin's Lymphoma in Minnesota , 2000, Archives of environmental health.

[13]  W. Willett,et al.  Dietary fat and protein in relation to risk of non-Hodgkin's lymphoma among women. , 1999, Journal of the National Cancer Institute.

[14]  G. Law,et al.  Non-Hodgkin's lymphoma and nitrate in drinking water: a study in Yorkshire, United Kingdom. , 1999, Journal of epidemiology and community health.

[15]  J. Dallinga,et al.  Volatile N-nitrosamine formation after intake of nitrate at the ADI level in combination with an amine-rich diet. , 1998, Environmental health perspectives.

[16]  A R Tricker,et al.  N-nitroso compounds and man: sources of exposure, endogenous formation and occurrence in body fluids. , 1997, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[17]  D. Weisenburger,et al.  Drinking Water Nitrate and the Risk of Non‐Hodgkin's Lymphoma , 1996, Epidemiology.

[18]  G. Block,et al.  Revision of dietary analysis software for the Health Habits and History Questionnaire. , 1994, American journal of epidemiology.

[19]  H. Bartsch,et al.  Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. , 1994, Mutation research.

[20]  T C Campbell,et al.  Geographic association between urinary excretion of N‐nitroso compounds and oesophageal cancer mortality in china , 1993, International journal of cancer.

[21]  T. Maynard,et al.  N-nitrosoproline excretion by rural Nebraskans drinking water of varied nitrate content. , 1992, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[22]  D. Weisenburger,et al.  2-Hydroxyethylnitrosourea induction of B cell lymphoma in female Swiss mice. , 1990, Cancer letters.

[23]  H. Autrup,et al.  Endogenous nitrosation in relation to nitrate exposure from drinking water and diet in a Danish rural population. , 1988, Cancer research.

[24]  H. Bartsch,et al.  Inhibitors of endogenous nitrosation. Mechanisms and implications in human cancer prevention. , 1988, Mutation research.

[25]  D. Weisenburger,et al.  Carcinogenicity of 1-(2-hydroxyethyl)-1-nitrosourea and 3-nitroso-2-oxazolidinone administered in drinking water to male MRC-Wistar rats: induction of bone, hematopoietic, intestinal, and liver tumors. , 1987, Journal of the National Cancer Institute.

[26]  D. Forman.  Dietary exposure to N-nitroso compounds and the risk of human cancer. , 1987, Cancer surveys.

[27]  H. Bartsch,et al.  Urinary excretion of N-nitrosamino acids and nitrate by inhabitants in high- and low-risk areas for stomach cancer in northern Japan. , 1987, IARC scientific publications.

[28]  G Block,et al.  A data-based approach to diet questionnaire design and testing. , 1986, American journal of epidemiology.

[29]  M. Blettner,et al.  Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for esophageal cancer in Northern China: endogenous formation of nitrosoproline and its inhibition by vitamin C. , 1986, Cancer research.

[30]  H. Inskip,et al.  A survey of dietary nitrate in well-water users. , 1984, International journal of epidemiology.

[31]  P. Bogovski,et al.  Special report animal species in which n‐nitroso compounds induce cancer , 1981, International journal of cancer.

[32]  G. Eisenbrand,et al.  Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. , 1976, Food and cosmetics toxicology.