Adenocarcinoma of the stomach and esophagus and drinking water and dietary sources of nitrate and nitrite

We conducted a population-based case-control study of adenocarcinoma of the stomach and esophagus in Nebraska, U.S.A. Nitrate concentrations in public drinking water supplies were linked to residential water source histories. Among those using private wells at the time of the interview, we measured nitrate levels in water samples from wells. Dietary nitrate and nitrite were estimated from a food-frequency questionnaire. Among those who primarily used public water supplies (79 distal stomach, 84 esophagus, 321 controls), average nitrate levels were not associated with risk (highest versus lowest quartile: stomach OR=1.2, 95% CI [0.5-2.7]; esophagus OR=1.3, 95% CI [0.6-3.1]). We observed the highest ORs for distal stomach cancer among those with higher water nitrate ingestion and higher intake of processed meat compared with low intakes of both; however, the test for positive interaction was not significant (p=0.213). We did not observe this pattern for esophagus cancer. Increasing intake of nitrate and nitrite from animal sources was associated with elevated ORs for stomach cancer and with a significant positive trend in risk of esophagus cancer (P-trend=0.325 and 0.015, respectively). Larger studies with higher exposures to drinking water sources of nitrate are warranted to further evaluate N-nitroso compound precursors as risk factors for these cancers.     

Is nitrate in the drinking water associated with the risk of cancer in the urban UK?

Several studies have suggested that nitrate levels in drinking water may be linked with stomach cancer. Recent investigations of this hypothesis in rural areas of the UK, where nitrate levels can be high, have been inconclusive. The present study examined mortality data for the years 1969-1973 in 253 urban areas in relation to treated water nitrate levels. Variations in socioeconomic status and urban area size were taken into account. Drinking water nitrate levels were negatively associated with mortality from stomach cancer even when the analysis was restricted to urban areas with nitrate levels above the EEC guide. There was no evidence of a positive association between nitrate in the drinking water and the risk of stomach cancer in the urban areas of the UK, an important finding for the British water industry.     

Association between gastric cancer mortality and nitrate content of drinking water: Ecological study on small area inequalities

The carcinogenic feature of N-nitroso compounds has been well established. Similarly, the transformation of ingested nitrate to N-nitroso compounds in the stomach has been thoroughly documented, nevertheless nitrates' carcinogenic effect has not been proved convincingly in human. The present study was aimed to investigate a population of small villages provided by drinking water with high and widely variable nitrate content (72 mg/l median, 290.7 mg/l 95-percentile concentration). Empirical Bayes estimates for settlement-specific age-, sex-, and year-standardised mortality ratios of gastric cancer (GC) were related to the settlement level average nitrate concentrations in drinking water controlling for confounding effects of smoking, ethnicity and education. The log-transformed average nitrate concentration showed significant positive association with stomach cancer mortality in linear regression analysis (p = 0.014). The settlements were aggregated according to the nitrate concentration into 10-percentile groups and the standardised mortality ratios (SMRs) were calculated. Those groups with higher than 88 mg/l average nitrate concentration showed substantial risk elevation and the log-transformed exposure variables proved to be significant predictors of mortality (p equals; 0.032) at this level of aggregation also. The association seemed to be fairly strong (r ² equals; 0.46). Although this investigation constituting an ecological study has certain limitations, it supports the hypothesis that the high level of nitrate in drinking water is involved in the development of GC.     

Nitrate in drinking water and cancer in northern Jutland,Denmark, with special reference to stomach cancer

Nitrate ingestion has been suggested to be associated with an increased risk of stomach cancer possibly through endogenous nitrosamine formation. The town of Aalborg in the northeast Jutland of Denmark (population approx 100,000) has been known for decades to have an average concentration of approx 30 mg/liter nitrate in its drinking waters. Age-standardized cancer incidence rates for 1943–1972 for various types of cancer were compared between Aalborg, neighboring towns, and all Danish provincial towns. During this 30-year period stomach cancer occurred slightly more frequently in Aalborg than in the town of Aarhus (population approx 200,000), with average standardized incidence ratios of 1.25 among men and 1.20 among women. It is unlikely than the increased incidence of stomach cancer in Aalborg may be explained by diagnostic differences, socioeconomic differences, or differences in dietary or constitutional factors. It is concluded that the results support a possible weak role for nitrate in the etiology of stomach cancer. Decreasing stomach cancer incidence in Aalborg as well as in other towns of Denmark indicate that nitrate may be only one of several factors influencing stomach cancer development.     

An ecologic study of nitrate in municipal drinking water and cancer incidence in Trnava District,Slovakia

Contamination of drinking water by nitrate is an evolving public health concern since nitrate can undergo endogenous reduction to nitrite, and nitrosation of nitrites can form N-nitroso compounds, which are potent carcinogens. We conducted an ecologic study to determine whether nitrate levels in drinking water were correlated with non-Hodgkin lymphoma and cancers of the digestive and urinary tracts in an agricultural district (Trnava District; population 237,000) of the Slovak Republic. Routinely collected nitrate data (1975-1995) for villages using public water supplies were computerized, and each village was categorized into low (0-10 mg/L), medium (10.1-20 mg/L), or high (20.1-50 mg/L) average levels of total nitrate in drinking water. Observed cases of cancer in each of these villages were ascertained through the district cancer registry for the time period 1986-1995. Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) for all cancer and selected cancer sites were calculated by indirect standardization using age- and sex-specific incidence rates from the entire district. For all cancer in women, SIRs increased from villages with low (SIR=0.87; 95% CI 0.72-0.95) to medium (SIR=1.07; 95% CI 1.00-1.13) to high (SIR=1.14; 1.06-1.22) levels of nitrate (P for trend <0.001); there was a similar trend for all cancer in men from low (SIR=0.90; 95% CI 0.81-0.99) to medium (SIR=1.08, 95% CI 1.02-1.16), but not for high (SIR=0.94; 0.88-1.02), nitrate levels (P for trend <0.001). This pattern in the SIRs (from low to high nitrate level) was also seen for stomach cancer in women (0.81, 0.94, 1.24; P for trend=0.10), colorectal cancer in women (0.64, 1.11, 1.29; P for trend <0.001) and men (0.77, 0.99, 1.07; P for trend=0.051), and non-Hodgkin lymphoma in women (0.45, 0.90, 1.35; P for trend=0.13) and men (0.25, 1.66, and 1.09; P for trend=0.017). There were no associations for kidney or bladder cancer. These ecologic data support the hypothesis that there is a positive association between nitrate in drinking water and non-Hodgkin lymphoma and colorectal cancer.     

Nitrogen-nitrate exposure from drinking water and colorectal cancer risk for rural women in Wisconsin, USA

One unintentional result of widespread adoption of nitrogen application to croplands over the past 50 years has been nitrate contamination of drinking water with few studies evaluating the risk of colorectal cancer. In our population-based case-control study of 475 women age 20–74 years with colorectal cancer and 1447 community controls living in rural Wisconsin, drinking water nitrate exposure were interpolated to subjects residences based on measurements which had been taken as part of a separate water quality survey in 1994. Individual level risk factor data was gathered in 1990–1992 and 1999–2001. Logistic regression models estimated the risk of colorectal cancer for the study period, separately and pooled. In the pooled analyses, an overall colorectal cancer risk was not observed for exposure to nitrate-nitrogen in the highest category (10 ppm) compared to the lowest category (<0.5 ppm). However, a 2.9 fold increase risk was observed for proximal colon cancer cases in the highest compared to the lowest category. Statistically significant increased distal colon or rectal cancer risk was not observed. These results suggest that if an association exists with nitrate-nitrogen exposure from residential drinking water consumption, it may be limited to proximal colon cancer.     

Pancreatic cancer and drinking water and dietary sources of nitrate and nitrite

N-Nitroso compounds, known animal carcinogens, are formed endogenously from drinking water and dietary sources of nitrate and nitrite. The authors conducted a population-based case-control study of pancreatic cancer in Iowa to determine whether increased consumption of nitrate and nitrite from drinking water and dietary sources was associated with risk. They linked detailed water source histories to nitrate measurements for Iowa community water supplies. After exclusions for insufficient data, 1,244 controls and 189 pancreatic cancer cases were available for analysis. Among controls, the median average nitrate level (1960-1987) was 1.27 (interquartile range, 0.6-2.8) mg of nitrate nitrogen per liter of water. No association was observed between pancreatic cancer risk and increasing quartiles of the community water supplies' nitrate level. Increasing intake of dietary nitrite from animal sources was associated with an elevated risk of pancreatic cancer among men and women (highest quartile odds ratios = 2.3, 95% confidence interval: 1.1, 5.1, for men and 3.2, 95% confidence interval: 1.6, 6.4, for women). In contrast, dietary nitrate intake showed an inverse association with risk among women and no association among men. This study suggests that long-term exposure to drinking water nitrate at levels below the maximum contaminant level of nitrate nitrogen (10 mg/liter) is not associated with pancreatic cancer; however, the consumption of dietary nitrite from animal products may increase risk.     

Bronchiectasis in persons with skin lesions resulting from arsenic in drinking water

BACKGROUND: Arsenic is a unique human carcinogen in that it causes lung cancer by exposure through ingestion (in drinking water) as well as through inhalation. Less is known about nonmalignant pulmonary disease after exposure to arsenic in drinking water. METHODS: We recruited 108 subjects with arsenic-caused skin lesions and 150 subjects without lesions from a population survey of over 7000 people in an arsenic-exposed region in West Bengal, India. Thirty-eight study participants who reported at least 2 years of chronic cough underwent high-resolution computed tomography (CT); these scans were read by investigators in India and the United States without knowledge of the presence or absence of skin lesions. RESULTS: The mean (+/-standard deviation) bronchiectasis severity score was 3.4 (+/-3.6) in the 27 participants with skin lesions and 0.9 (+/-1.6) in the 11 participants without these lesions. In subjects who reported chronic cough, CT evidence of bronchiectasis was found in 18 (67%) participants with skin lesions and 3 (27%) subjects without skin lesions. Overall, subjects with arsenic-caused skin lesions had a 10-fold increased prevalence of bronchiectasis compared with subjects who did not have skin lesions (adjusted odds ratio=10; 95% confidence interval=2.7-37). CONCLUSIONS: These results suggest that, in addition to being a cause of lung cancer, ingestion of high concentrations of arsenic in drinking water may be a cause of bronchiectasis.     

Impact of nitrates in drinking water on cancer mortality in Valencia,Spain

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. Thus, in populations with nitrate concentrations in excess of 50 mg/1, relative risk for gastric cancer in the 55–75 years age group was 1.91 and 1.81 for males and females, respectively (p<0.05). In the case of prostate cancer elevated relative risks were also encountered: 1.86 and 1.80 for the 55–75 and over 75 years age groups, respectively.     

赞皇县胃癌高发区饮用水的微核效应观察

Mutagenicity/Carcinogenicity of samples of drinking water supplies in the high risk area of stomach cancer was studied with micronucleus test and the epidemiologic method in Zanhuang county, Hebei. The results showed that the micronucleus cell rates in NIH mice induced by concentrated drinking water samples from the high risk area of stomach cancer were higher than those from low risk area and there was close correlation between degree of water concentration and micronucleus cell rates. This corresponded with the results obtained by the epidemiological method showed that the drinking water was obviously mutagenic and that it was closely correlated with the production of stomach cancer.