President's Cancer Panel Meeting: Environmental Factors in Cancer, Transcript of Proceedings, Indianapolis, in, Oc by National Cancer Institute - HTML preview

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Key Points

Nitrate mainly comes from fertilizers applied in the agricultural environment; it is extremely beneficial for productivity. However, the input of nitrogen into the environment also goes up with increases in the human population. Because of this increased “human input,” the

nitrogen cycle has dramatically changed.

Nitrogen constitutes 80 percent of the atmosphere; plants take up nitrogen through roots in the soil, and to a lesser extent from light. In the twentieth century, the Haber-Bosch process was introduced to take nitrogen out of the atmosphere and convert it to reactive nitrogen in

the form of nitrate and ammonium fertilizers. As a result of the input of nitrate fertilizers into the soil, the amount of nitrate in ground water has risen.

The EPA regulates nitrate at a maximum contaminate level (MCL) of 10 milligrams per liter (of nitrate nitrogen). This standard was set based on the acute health effect

methemoglobinemia, but other chronic health effects have not been studied at this level. EPA

regulates public water supplies by this standard, but private wells, which are not regulated, tend to have much higher levels. In agricultural states it is estimated that 20 to 25 percent of the population is exposed to nitrate in drinking water at about half the MCL. About 22

percent of private wells in these areas exceed the MCL.

Nitrate ingested from drinking water, dark green leafy and root vegetables, and processed meats is absorbed in the body, then secreted through active transport into the saliva where

oral bacteria reduce it to nitrite. The nitrite is swallowed and can react with amines and

amides—found in proteins consumed—in the stomach to form nitroso compounds. The

endogenous formation of nitroso compounds is catalyzed by heme iron—red meat increases

production of the compounds. However, fruits and vegetables high in vitamin C or E inhibit

the process. In 2006, IARC concluded that ingested nitrite and nitrate are probably

carcinogenic to humans under conditions that result in endogenous nitrosation in the body.

Over 300 nitroso compounds have been tested and 90 percent have been found to be

carcinogenic in 39 animal species, including six primate species.

A majority of IARC case-control studies show an association between dietary nitrite (largely from processed meats) and stomach cancer, with one or two also showing an association with

esophageal cancer. A recent international review of the literature on diet and cancer found

convincing evidence of increased colon cancer risk in relation to intake of both red and

processed meats.

Indianapolis, IN

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October 21, 2008

Recent population-based case-control studies in agricultural states such as Iowa and

Nebraska, where nitrate levels are elevated in public and private water supplies, have

improved epidemiologic study designs. Historical databases of public monitoring data for

nitrate were used in combination with food frequency questionnaires modified to estimate

dietary nitrate. These studies were able to evaluate factors that increase nitrosation in

humans—lower vitamin C and higher red meat intake. One study, a case-control of renal cell

carcinoma in Iowa, found a twofold increased risk among those who had longer-duration

exposure to nitrate in drinking water and were above the median intake of red meat.

A multicenter, population-based case-control study in the western United States assessed the drinking water source of the mother during pregnancy and its link to childhood brain cancer.

The study found that, in Washington State, the offspring of mothers who used water from

private wells during pregnancy had increased risk of brain cancer.

Another possible mechanism by which nitrate could cause cancer is through the thyroid; at higher levels nitrates inhibit iodide uptake by the thyroid. A study in the Netherlands in the 1990s showed a relationship between nitrate in drinking water and thyroid hypertrophy and

hypoplasia in women.

Future studies should take into account dietary sources of nitrate, nitrosation inhibitors and precursors, and medical conditions that increase nitrosation to accurately assess cancer risk.

DISCUSSION: