Nitrate contamination of drinking water may increase cancer risk, because nitrate is endogenously reduced to nitrite and subsequent nitrosation reactions give rise to N-nitroso compounds; these compounds are highly carcinogenic and can act systemically. We analyzed cancer incidence in a cohort of 21,977 Iowa women who were 55-69 years of age at baseline in 1986 and had used the same water supply more than 10 years (87% > 20 years); 16,541 of these women were on a municipal supply, and the remainder used a private well. We assessed nitrate exposure from 1955 through 1988 using public databases for municipal water supplies in Iowa (quartile cutpoints: 0.36, 1.01, and 2.46 mg per liter nitrate-nitrogen). As no individual water consumption data were available, we assigned each woman an average level of exposure calculated on a community basis; no nitrate data were available for women using private wells. Cancer incidence (N = 3,150 cases) from 1986 through 1998 was determined by linkage to the Iowa Cancer Registry. For all cancers, there was no association with increasing nitrate in drinking water, nor were there clear and consistent associations for non-Hodgkin lymphoma; leukemia; melanoma; or cancers of the colon, breast, lung, pancreas, or kidney. There were positive associations for bladder cancer [relative risks (RRs) across nitrate quartiles = 1, 1.69, 1.10, and 2.83] and ovarian cancer (RR = 1, 1.52, 1.81, and 1.84), and inverse associations for uterine cancer (RR = 1, 0.86, 0.86, and 0.55) and rectal cancer (RR = 1, 0.72, 0.95, and 0.47) after adjustment for a variety of cancer risk/protective factors, agents that affect nitrosation (smoking, vitamin C, and vitamin E intake), dietary nitrate, and water source. Similar results were obtained when analyses were restricted to nitrate level in drinking water from 1955 through 1964. The positive association for bladder cancer is consistent with some previous data; the associations for ovarian, uterine, and rectal cancer were unexpected.

Municipal Drinking Water Nitrate Level and Cancer Risk in Older Women: The Iowa Women’s Health Study

Epidemiologic evidence on the relation between contaminants in drinking water and cancer is reviewed. The reviewed studies cover exposure to: disinfection byproducts; nitrate; arsenic and other metals; volatiles and contaminants from hazardous waste sites; asbestiform fibers; radionuclides; and fluoride. Most investigations are ecologic, with some confirmation of elevated risk from individual-based studies. In the case of waterborne arsenic, and possibly chlorination byproducts, there is a consistent but small body of epidemiologic evidence of an association with one or more types of cancer. Nitrate in groundwater has increased greatly over the years, and the demonstration of endogenous nitrosation among highly exposed subjects raises concern of elevated cancer risk. However, the epidemiologic data are not yet sufficient to draw a conclusion. There is a diversity of studies among populations exposed to water contaminated with pesticides, volatile organics, or mixtures from hazardous waste sites. Studies of asbestiform fibers and radionuclides in water are not conclusive, but there are suggested elevations of several cancer sites in highly exposed populations. There is no suggestion that fluoride in drinking water is linked with elevated risk of cancer. As topics for epidemiologic evaluation, drinking water contaminants pose methodologic problems common to studies designed to detect relatively small elevations in risk, with the added challenge of assessing exposures for many years in the past. Nevertheless, epidemiologic assessment is valuable and clearly warranted, given the potential public health impact of small risk elevations among very large exposed populations, and the limitations of toxicologic experiments in assessing carcinogenic risk of complex mixtures or of compounds for which appropriate animal models are not available.

Drinking water and cancer

Based on the premise that dietary nitrate is detrimental to human health, increasingly stringent regulations are being instituted to lower nitrate levels in food and water. Not only does this pose a financial challenge to water boards and a threat to vegetable production in Northern Europe, but also may be eliminating an important non-immune mechanism for host defence. Until recently nitrate was perceived as a purely harmful dietary component which causes infantile methaemoglobinaemia, carcinogenesis and possibly even teratogenesis. Epidemiological studies have failed to substantiate this. It has been shown that dietary nitrate undergoes enterosalivary circulation. It is recirculated in the blood, concentrated by the salivary glands, secreted in the saliva and reduced to nitrite by facultative Gram-positive anaerobes (Staphylococcus sciuri and S. intermedius) on the tongue. Salivary nitrite is swallowed into the acidic stomach where it is reduced to large quantities of NO and other oxides of N and, conceivably, also contributes to the formation of systemic S-nitrosothiols. NO and solutions of acidified nitrite, mimicking gastric conditions, have been shown to have antimicrobial activity against a wide range of organisms. In particular, acidified nitrite is bactericidal for a variety of gastrointestinal pathogens such as Yersinia and Salmonella. NO is known to have vasodilator properties and to modulate platelet function, as are S-nitrosothiols. Thus, nitrate in the diet, which determines reactive nitrogen oxide species production in the stomach (McKnight et al. 1997), is emerging as an effective host defence against gastrointestinal pathogens, as a modulator of platelet activity and possibly even of gastrointestinal motility and microcirculation. Therefore dietary nitrate may have an important therapeutic role to play, not least in the immunocompromised and in refugees who are at particular risk of contracting gastroenteritides.

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Dietary nitrate in man: friend or foe?

An Ecologic Study of Nitrate in Municipal Drinking Water and Cancer Incidence in Trnava District, Slovakia

Dietary intake of nitrate generates salivary nitrite, which is acidified in the stomach, leading to a number of reactive intermediates of nitrogen, among which are the potentially carcinogenic N-nitrosamines. Acidified nitrite, however, also has antimicrobial activity which coincides with the formation of nitric oxide. The present study examines the antimicrobial effect in vitro of acidified nitrite on Salmonella enteritidis, Salmonella typhimurium, Yersinia enterocolitica, Shigella sonnei, and Escherichia coli O157. First-order regression plots showed a linear inverse relationship of log-transformed proton and nitrite concentrations with MICs and MBCs after 30 min, 2 h, and 24 h of exposure (P S. enteritidis > S. typhimurium = Shigella sonnei > E. coli O157 (P < 0.05). Addition of SCN-, but not that of CI-, increased the antibacterial activity (paired t testing, P < 0.001). Generation of salivary nitrite from dietary nitrate may provide significant protection against gut pathogens in humans.

Geleperin A

Papers

Nitrate in water supplies and cancer.