The relationship between nitrate levels in drinking water and bladder cancer development is controversial. A matched cancer case-control with nitrate ecology study was used to investigate the association between bladder cancer mortality occurrence and nitrate exposure from Taiwan drinking water. All bladder cancer deaths of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on nitrate-nitrogen (NO3-N) levels in drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high nitrate levels in their drinking water were 1.76 (1.28-2.42) and 1.96 (1.41-2.72) as compared to the lowest tertile. The results of the present study show that there was a significant positive relationship between the levels of nitrate in drinking water and risk of death from bladder cancer.

Source: Journal Of Environmental Pathology, Toxicology And Oncology: Official Organ Of The International Society For Environmental Toxicology And Cancer [J Environ Pathol Toxicol Oncol] 1993 Oct-Dec; Vol. 12 (4), pp. 229-36.

Environmental contamination is a characteristic of industrialized nations. The quality of public drinking water, particularly from underground reserves, has increasingly deteriorated. The fundamental cause of the contamination of underground water layers has been the growing worldwide use of nitrogen fertilizers and pesticides since the 1960s. The Valencian Community comprises three provinces on the East Mediterranean coast of Spain. Public drinking water in this community is obtained chiefly from underground sources. As a result, this area suffers the highest nitrates contamination of public drinking water recorded not only in Spain but in all of Europe. The aim of the present study was to investigate the existence of differences in the occurrence of bladder cancer between the population of Valencia province and the rest of the country. We studied the differences in bladder cancer incidence among populations exposed to different levels of nitrates in drinking water in the province of Valencia, as expressed in terms of relative risk. We found a statistically significant difference (p < 0.0001) between the occurrence of bladder cancer in the Valencia province and the rest of Spain, as reflected by the analysis of the corresponding regression curve slopes. Our analytical study revealed relative risks of over 1 in Valencia province in men and women, associated with the consumption of water containing a mean concentration of > 50 mg/L.

Source: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA. wardm@mail.nih.gov.

Human alteration of the nitrogen cycle has resulted in steadily accumulating nitrate in our water resources. The U.S. maximum contaminant level and World Health Organization guidelines for nitrate in drinking water were promulgated to protect infants from developing methemoglobinemia, an acute condition. Some scientists have recently suggested that the regulatory limit for nitrate is overly conservative; however, they have not thoroughly considered chronic health outcomes. In August 2004, a symposium on drinking-water nitrate and health was held at the International Society for Environmental Epidemiology meeting to evaluate nitrate exposures and associated health effects in relation to the current regulatory limit. The contribution of drinking-water nitrate toward endogenous formation of N-nitroso compounds was evaluated with a focus toward identifying subpopulations with increased rates of nitrosation. Adverse health effects may be the result of a complex interaction of the amount of nitrate ingested, the concomitant ingestion of nitrosation cofactors and precursors, and specific medical conditions that increase nitrosation. Workshop participants concluded that more experimental studies are needed and that a particularly fruitful approach may be to conduct epidemiologic studies among susceptible subgroups with increased endogenous nitrosation. The few epidemiologic studies that have evaluated intake of nitrosation precursors and/or nitrosation inhibitors have observed elevated risks for colon cancer and neural tube defects associated with drinking-water nitrate concentrations below the regulatory limit.

Source: International Journal Of Epidemiology [Int J Epidemiol] 2004 Dec; Vol. 33 (6), pp. 1209-16. Date of Electronic Publication: 2004 Nov 26.

The period in utero is a time of increased vulnerability. Offspring of pregnant women exposed to carcinogenic substances in drinking water may be more likely to develop cancer. We examined whether household water source and the presence of nitrates or nitrites in residential water were associated with increased risks of childhood brain tumors (CBT). METHODS: We used data from a multicentre, case-control study with maternal information on residential water source, and nitrate/nitrite levels of tap water measured by dipstick. Subjects included 836 CBT cases and 1485 controls from five countries. RESULTS: The risks of CBT associated with reliance on well water (versus public water) during pregnancy varied widely, with significantly increased risks noted in two (of seven) regions and a decreased risk observed in one region. CBT risk did not increase with increasing nitrate levels. However, our results based on tap water tested in the pregnancy residences suggest the risk of astrocytoma may be associated with increasing levels of nitrite (odds ratio [OR] = 4.3, 95% CI: 1.4, 12.6 for nitrite levels of 1-<5 mg/l nitrite ion; OR = 5.7, 95% CI: 1.2, 27.2 of nitrite > or =5 mg/l). CONCLUSIONS: These results should be interpreted with caution because women's recollection of water sources may have contained inaccuracies, and nitrate and nitrite measurements, available for only a portion of subjects, were often obtained years after the pregnancies occurred. However, our results suggest a need for closer evaluation of well water content in some regions and the possibility that a nitrite-related water exposure may be associated with CBT.

The possible association between the risk of gastric cancer and the levels of calcium, magnesium, and nitrate in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Records of gastric cancer deaths among eligible residents in Taiwan from 1987 through 1991 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by sex, year-of-birth, and year-of-death. Each matched control was selected randomly from the set of possible controls for each case. Data on calcium, magnesium, and nitrate levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation. The municipality of residence of the cases and controls was assumed to be the source of the subject's calcium, magnesium, and nitrate exposure via drinking water. The subjects were divided into tertiles according to the levels of calcium, magnesium, and nitrate in their drinking water. The results of the present study show that there is a significant positive association between drinking water nitrate exposure and gastric cancer mortality. The present study also suggests that there was a significant protective effect of calcium intake from drinking water on the risk of gastric cancer. Magnesium also exerts a protective effect against gastric cancer, but only for the group with the highest levels.

Source: Epidemiology (Cambridge, Mass.) [Epidemiology] 1996 Sep; Vol. 7 (5), pp. 465-71.

The increasing incidence of non-Hodgkin's lymphoma (NHL) in the United States is only partially explained by known risk factors. Nitrate is a contaminant of drinking water in many rural areas. We evaluated its association with NHL after accounting for dietary nitrate intake. For 156 cases and 527 controls who used Nebraska community supplies, average nitrate exposure was estimated from 1947 through 1979. Longterm consumption of community water with average nitrate levels in the highest quartile (> or = 4 mg per liter nitrate-nitrogen) was positively associated with risk [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.1-3.6]. Dietary nitrate, which came mainly from vegetables, was not associated with NHL risk, after adjusting for vitamin C and carotene intakes. Persons with a lower intake of vitamin C were at slightly higher risk of developing NHL than persons whose daily intake was > or = 130 mg, for all levels of intake of drinking water nitrate; our findings were similar for the combined effect of water nitrate and carotene intake. Nitrate levels in private wells were measured at the time of the interview for 51 cases and 150 controls but were not associated with the risk of NHL after adjusting for pesticide use on the farm. These findings indicate that longterm exposure to elevated nitrate levels in drinking water may contribute to the risk of NHL.

Source: The Nebraska Medical Journal [Nebr Med J] 1993 Jan; Vol. 78 (1), pp. 7-12.

Ground water serves as the primary source of drinking water for nearly all of rural Nebraska. However, ground-water contamination by nitrates, largely due to the use of fertilizers, is an increasing problem. In an ecologic study, the author found that counties characterized by high fertilizer usage and significant ground-water contamination by nitrates also had a high incidence of non-Hodgkin's lymphoma. Other potential health effects of nitrates in drinking water are also discussed.

The concentrations of nitrates in public drinking water in the Mediterranean coastal province of Valencia are not only the highest in Spain but also in the whole of Europe. Intensive agricultural practices involve a traditional and growing use of nitrogen fertilizers. This and the terrain--poorly consolidated and porous in areas--favors the accumulation of nitrates in underground aquifers, thereby perhaps accounting for this contamination. The possible conversion of nitrates to nitrites under certain conditions of gastric achlorhydria, followed by their transformation to nitrosamines--substances known to be carcinogenic in experimental models--has led to a number of epidemiological studies of the possible relationship between high nitrate levels in public drinking water and mortality due to different cancers. The aim of the present study was to analyze the relationship between different levels of exposure to nitrates in the drinking water of the 258 municipalities in the province of Valencia and mortality due to cancer of the stomach, bladder, prostate and colon in this population. The cancer mortality rate was found to rise with increasing exposure to nitrates in the case of gastric cancer in both sexes, and in prostate cancer. These same results were obtained on calculating relative risk for the different age groups associated with the consumption of drinking water containing different levels of nitrates.

Iowa Women's Health Study Links Cancer Risk with Nitrate Levels in Drinking Water

Background: Nitrate contamination of drinking water has been documented in many areas of the United States. The source of the nitrate has been attributed to widespread use of commercial fertilizers as well as animal and human wastes. In Iowa, the use of fertilizers in both rural and urban settings has resulted in 30-40% of the public water supply with nitrate concentrations greater than 5 mg/liter. The EPA limit for nitrate in drinking water is 10mg/liter primarily to prevent methemoglobinemia in infants. However, other health risks of nitrate exposure have not been fully evaluated against this standard.

These investigators were interested in evaluating nitrate consumption and cancer risk. Nitrates are converted to highly carcinogenic N-nitroso compounds in the digestive track. An epidemiologic study was conducted using the Iowa Women's Health Study cohort. Drinking water source is but one of the many issues this study tracks and with over 40,000 women enrolled, it is an excellent resource for this type of investigation.

Advance: As in previous studies, these investigators found a positive association between nitrate exposure and bladder cancer. Unexpectedly, they also found a positive association for ovarian cancer. In addition, they reported a negative association for uterine and rectal cancer. All associations appear to be dose dependent. There were no associations for all other cancer types examined.

Implication: Results from these studies correlate with earlier studies that show increased risk for bladder cancer as nitrate level in drinking water rises. The unexpected positive association with ovarian cancer and the even more unexpected negative associations for uterine and rectal cancer suggest that nitrate levels below the current EPA standard in municipal water supplies are of significant public health concern. Additional research is necessary to fully understand this issue and to make standards to protect public health.