Does calcium in drinking water modify the association between nitrate in drinking water and risk of death from colon cancer?

The objective of this study was to explore whether calcium (Ca) levels in drinking water modified the effects of nitrate on colon cancer risk. A matched case–control study was used to investigate the relationship between the risk of death from colon cancer and exposure to nitrate in drinking water in Taiwan. All colon cancer deaths of Taiwan residents from 2003 through 2007 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. Information on the levels of nitrate-nitrogen (NO₃-N) and Ca in drinking water have been collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's NO₃-N and Ca exposure via drinking water. We observed evidence of an interaction between drinking water NO₃-N and Ca intake via drinking water. This is the first study to report effect modification by Ca intake from drinking water on the association between NO₃-N exposure and risk of colon cancer mortality.     

Nitrate in public water supplies and risk of bladder cancer

BACKGROUND: Nitrate is a precursor compound in the formation of N-nitroso compounds, most of which are potent animal carcinogens. N-nitroso compounds and their precursors have not been extensively evaluated as bladder cancer risk factors. METHODS: We conducted a population-based case-control study of bladder cancer in Iowa. Cases were men and women newly diagnosed with bladder cancer in 1986-1989. Nitrate data for Iowa public water supplies were sparse before the 1960s. To reduce misclassification by unknown nitrate levels, we included only those who used public supplies with nitrate data for 70% or more of their person-years since 1960 (808 cases, 1259 controls). RESULTS: Among controls, the median average nitrate level for their Iowa residences with public water supplies was 1.3 mg/liter nitrate-nitrogen (interquartile range = 0.6-3.0). After adjustment for confounders, we found no increased risk of bladder cancer with increasing average nitrate levels in drinking water; the highest quartile odds ratio for women was 0.8 (95% confidence interval = 0.4-0.8), and for men 0.5 (0.4-0.8). We observed no association among those with high water nitrate exposure (>median) and low (相似文献   

Tea consumption and the risk of colorectal cancer in Sweden.

The association between tea drinking and colorectal cancer risk remains unclear. The evidence for black tea is sparse but may indicate an increased risk with regular use. Because black tea is a common beverage in many populations, the significant twofold increased risk of colon cancer recently reported from a large prospective cohort of male Finnish smokers is disconcerting. Using Cox proportional hazards models to estimate relative risks, we examined this association in a large, population-based prospective cohort study in Sweden. During an average 9.6 years of follow-up of our cohort of 61,463 women (588,270 person-yr), we observed 460 incident cases of colorectal cancer (291 colon, 159 rectal, and 10 with both colon and rectal cancer). We observed no association between tea consumption and combined colorectal cancers in age- or multivariate-adjusted models. With the use of collapsed exposure categories, the multivariate-adjusted relative risk for the highest exposure (> or = cups/day) compared with the lowest (never or seldom) was 0.97 (95% confidence interval = 0.63-1.48, p for trend = 0.34). Examining the association by cancer subsite, we observed no association between tea consumption and proximal, distal, or combined colon cancers. We did, however, observe a nonsignificant positive association with rectal cancers, which became stronger and statistically significant among women > or = 65 years of age at baseline. Our data do not support the strong, dose-dependent positive association with colon cancer found in the Finnish study.     

Mediterranean diet adherence and risk of colorectal cancer: the prospective Netherlands Cohort Study

Mediterranean diet (MD) adherence has been associated with a large variety of health benefits. However, prospective studies investigating the relation between MD adherence and colorectal cancer risk had inconsistent results. In this analysis of the Netherlands Cohort Study (NLCS), we evaluated sex- and subsite-specific associations of MD adherence with colorectal cancer risk. In 1986, 120,852 subjects filled out the NLCS baseline questionnaire, which incorporated a 150-item food frequency questionnaire. MD adherence was estimated through alternate Mediterranean diet scores including and excluding alcohol (aMED and aMEDr, respectively). Using 20.3 year follow-up data, 1993 male and 1574 female colorectal cancer cases could be included in multivariable case-cohort analyses. aMEDr was not significantly associated with colorectal cancer risk, regardless of sex. Hazard ratios (95% confidence intervals) per two-point increment were 1.04 (0.95–1.13) for men and 0.97 (0.88–1.07) for women. Additionally, there was no evidence of an inverse association with any of the colorectal cancer subsites (colon, proximal colon, distal colon, and rectum). In women, the association between aMEDr and colorectal cancer risk was significantly modified by smoking status (Pinteraction = 0.015). Comparable results were obtained for the original aMED including alcohol. In conclusion, higher MD adherence was not associated with a reduced risk of colorectal cancer or anatomical subsites in the context of a Dutch population.     

Gastric Cancer Mortality and Drinking Water Qualities in Taiwan

The possible association between the risk of gastric cancer and nitrate and hardness in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Data on gastric cancer deaths among eligible residents in Taiwan from 1987 through 1991 (6,766 cases) were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes (6,766 controls) and were matched individually to the cases by sex, year of birth, and year of death. Data on nitrate–nitrogen (NO₃–N) and hardness levels in drinking water throughout Taiwan were collected from the Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's nitrate and hardness exposure via drinking water. There was no difference in gastric cancer rates between the groups with different levels of nitrate. The odds ratios (95% confidence interval) for death from gastric cancer was 0.95 (0.87–1.03) for the group with water nitrate levels between 0.23 and 0.44 mg/L, and 1.02 (0.93–1.11) for the group with nitrate levels greater than 0.45 mg/L. However, the results show a significant negative relationship between drinking water hardness and gastric cancer mortality. Odds ratios were 1.16 (1.07–1.26) and 1.65 (1.52–1.79), respectively, for exposure to moderately hard water and soft water compared with the use of hard water. This is an important finding for the Taiwan water industry and human health risk. Received: 27 November 1996/Accepted: 16 April 1997     

Municipal drinking water nitrate level and cancer risk in older women: the Iowa Women's Health Study

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.     

Association between drinking water uranium content and cancer risk in Bavaria, Germany

Objective

To evaluate the possible association between uranium (U) content in public drinking water on the one hand and the risk of cancer of the colorectum, lung, female breast, prostate, kidney, and urinary bladder, total cancer, and leukemia on the other hand in Bavaria, an ecologic study on the level of municipalities was performed.

Methods

Cancer incidence data for the years 2002–2008 were obtained from the population-based cancer registry Bavaria according to sex. Current U content data of public drinking water on the level of municipalities were obtained from a publicly available source. The possible association between drinking water U content and cancer risk adjusted for average socio-economic status was evaluated using Poisson regression.

Results

Drinking water U content was below 20 μg/L in 458 out of 461 included municipalities. We found a significantly increased risk of leukemia in men in the intermediate (U level, 1.00–4.99 μg/L; relative risk [RR], 1.14) and in the highest U exposure category (U level, ≥5 μg/L; RR, 1.28). Moreover, in women, a significantly elevated risk was identified with respect to kidney cancer in the highest exposure category (RR, 1.16) and with respect to lung cancer in the intermediate exposure category (RR, 1.12).

Conclusion

The slightly increased risk of leukemia in men, kidney cancer in women, and lung cancer in women may require further investigation. If an increased cancer risk is confirmed, preventive measures (e.g., introduction of U filters in public water systems) may be considered.     

Association of dietary quercetin with reduced risk of proximal colon cancer

Quercetin is a flavonol that appears to be protective against several cancers, but its possible role in prevention of colorectal cancer is not yet well studied. We evaluated dietary intakes of quercetin and risk of colorectal cancer in a large case-control study conducted in metropolitan Detroit, Michigan (N = 2664). The protective effects of quercetin intake, as assessed by a food frequency questionnaire, were confined to risk of proximal colon cancer. Stratified analyses showed that the protective effects of quercetin on risk of proximal colon cancer were significant only when fruit intake or the Healthy Eating Index score was high, or when tea intake was low, with odds ratios (OR) for the highest vs. the lowest quartile of 0.49, 0.44, and 0.51, respectively. Increased quercetin intake had no protective effects when tea intake was high. Interestingly, increased intake of quercetin was associated with increased risk of distal colon cancer when total fruit intake was low (OR for the highest vs. the lowest quartile = 1.99). These results suggest that quercetin can have disparate effects on colon cancer risk depending on whether dietary intakes of fruit or tea are high, and that quercetin had protective effects only on proximal, not distal, colon cancer.     

五氯酚暴露与肿瘤风险关系的Meta分析

目的综合分析五氯酚暴露与肿瘤发生与死亡的流行病学资料,研究五氯酚暴露与肿瘤危险性之间的关系。方法通过在线检索文献资料,以Poisson回归分析方法探索五氯酚暴露人群的主要肿瘤死亡率,采用固定效应模型合并分析肿瘤SMR,并分析五氯酚暴露与肿瘤危险性之间的剂量-反应关系。结果美国、加拿大研究的暴露人群各主要肿瘤死亡率接近或低于所在国男性肿瘤死亡率;职业暴露人群的结直肠癌发病率为饮水摄食暴露人群的16.4倍;两国暴露人群肾癌合并SMR=1.34(95%CI=1.02~1.77);随着五氯酚暴露程度增加,各主要肿瘤死亡合并相对危险度(RR)随之升高。结论五氯酚暴露与肿瘤死亡风险间存有潜在的剂量-反应关系,职业暴露方式的结直肠癌风险高于饮水摄食暴露,五氯酚暴露可能为职业暴露人群肾癌死亡的危险因素。     

Serum albumin and colorectal cancer risk

OBJECTIVE: To study the relationship between serum albumin and colorectal cancer occurrence. DESIGN: A case-control study nested within a cohort followed from 1968 to 1991. SUBJECTS AND METHODS: The albumin concentration was determined from serum samples stored at -20 degrees C at baseline in 177 incident colorectal cancer cases and 288 controls matched for sex, age and study region. RESULTS: An elevated risk was present of cancer of the left, distal colon at high serum albumin concentrations. No significant association was observed for the right, proximal colon or the rectum. The relative risks of cancer of the distal and proximal colon among individuals in the highest and lowest quartiles of serum albumin were 17.03 (95% confidence interval 1.48-195) and 0.77 (95% confidence interval 0. 19-3.13), respectively. CONCLUSIONS: The present study lends support to the hypothesis that some dietary factor associated with serum albumin may be a risk factor for distal colon cancer.     

Total fluid and water consumption and the joint effect of exposure to disinfection by-products on risk of bladder cancer

BACKGROUND: Findings on water and total fluid intake and bladder cancer are inconsistent; this may, in part, be due to different levels of carcinogens in drinking water. High levels of arsenic and chlorinated by-products in drinking water have been associated with elevated bladder cancer risk in most studies. A pooled analysis based on six case-control studies observed a positive association between tap water and bladder cancer but none for nontap fluid intake, suggesting that contaminants in tap water may be responsible for the excess risk. OBJECTIVES: We examined the association between total fluid and water consumption and bladder cancer risk, as well as the interaction between water intake and trihalomethane (THM) exposure, in a large case-control study in Spain. METHODS: A total of 397 bladder cancer cases and 664 matched controls were available for this analysis. Odds ratios (OR) were estimated using unconditional logistic regression, controlling for potential confounders. RESULTS: Total fluid intake was associated with a decrease in bladder cancer risk [OR = 0.62; 95% confidence interval (CI), 0.40-0.95 for highest vs. lowest quintile comparison]. A significant inverse association was observed for water intake (for > 1,399 vs. < 400 mL/day, OR = 0.47; 95% CI, 0.33-0.66; p for trend < 0.0001), but not for other individual beverages. The inverse association between water intake and bladder cancer persisted within each level of THM exposure; we found no statistical interaction (p for interaction = 0.13). CONCLUSION: Findings from this study suggest that water intake is inversely associated with bladder cancer risk, regardless of THM exposure level.     

Fish consumption, n-3 fatty acids, and colorectal cancer: a meta-analysis of prospective cohort studies

Animal studies show favorable effects of n-3 fatty acids on inflammation and cancer, but results from epidemiologic studies appear to be inconsistent. The authors conducted meta-analyses of prospective cohort studies that evaluated the association between fish consumption or n-3 fatty acids and colorectal cancer incidence or mortality. Random-effects models were used, and heterogeneity between study results was explored through stratified analyses. The pooled relative risks for the highest compared with the lowest fish consumption category were 0.88 (95% confidence interval: 0.78, 1.00) for colorectal cancer incidence (14 studies) and 1.02 (95% confidence interval: 0.90, 1.16) for colorectal cancer mortality (four studies). The pooled relative risks for colorectal cancer incidence were 0.96 (95% confidence interval: 0.92, 1.00) for each extra occurrence of fish consumption per week (seven studies) and 0.97 (95% confidence interval: 0.92, 1.03) for each extra 100 g of fish consumed per week (four studies). Stratified analysis showed that the pooled relative risk for colorectal cancer incidence was more pronounced for women and in studies with a large exposure contrast. In cohort studies, fish consumption was shown to slightly reduce colorectal cancer risk. Existing evidence that n-3 fatty acids inhibit colorectal carcinogenesis is in line with these results, but few data are available addressing this association.     

Colon Cancer Mortality and Total Hardness Levels in Taiwan's Drinking Water

The possible association between the risk of colon cancer and hardness levels in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible colon cancer deaths (1,714 cases) of Taiwan residents from 1989 through 1993 were compared with deaths from other causes (1,714 controls) and the hardness levels of the drinking water used by these residents were determined. Data on water hardness throughout Taiwan have been collected from Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes and the controls were pair matched to the cases by sex, year of birth, and year of death. The results show a significant negative relationship between drinking water hardness and colon cancer mortality. Odds ratio and 95% confidence intervals were 1.22 (1.04–1.43) and 1.46 (1.22–1.75), respectively, for exposure to moderately hard water and soft water compared with the use of hard water. Trend analyses showed an increasing odds ratio for colon cancer with decreasing levels of hardness in drinking water. This is an important finding for the Taiwan water industry and human health. Received: 8 July 1997/Accepted: 29 November 1997     

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.     

Processed Meat and Colorectal Cancer Risk: A Pooled Analysis of Three Italian Case-Control Studies

To add evidence to the limited data available from southern Europe, we assessed the association between processed meat consumption and colorectal cancer risk. We analyzed data from three case-control studies conducted between 1985 and 2010 in various Italian areas, including a total of 3745 incident cases and 6804 hospital-based controls. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) by unconditional multiple logistic regression models. The median consumption of processed meat was around 20 g/day both in cases and controls. The OR of colorectal cancer was 1.02 (95% CI 0.99–1.04) for an increase of 10 g/day of processed meat. The association was statistically significant for colon cancer (OR 1.03, 95% CI 1.00–1.06), particularly for proximal colon cancer (OR 1.09, 95% CI 1.04–1.14), while there was no relation with rectal cancer (OR 0.99, 95% CI 0.95–1.03). The OR of proximal colon cancer was 1.38 (95% CI 1.08–1.75) for the highest sex-specific tertile of consumption (>25 g/day for men, >21.5 for women) compared with the lowest (<15 g/day), whereas no significant ORs were found for other anatomical subsites. Our findings indicate that there is no association with colorectal cancer overall, in the presence, however, of a positive association with proximal colon cancer.     

Does the evidence about health risks associated with nitrate ingestion warrant an increase of the nitrate standard for drinking water?

Several authors have suggested that it is safe to raise the health standard for nitrate in drinking water, and save money on measures associated with nitrate pollution of drinking water resources. The major argument has been that the epidemiologic evidence for acute and chronic health effects related to drinking water nitrate at concentrations near the health standard is inconclusive. With respect to the chronic effects, the argument was motivated by the absence of evidence for adverse health effects related to ingestion of nitrate from dietary sources. An interdisciplinary discussion of these arguments led to three important observations. First, there have been only a few well-designed epidemiologic studies that evaluated ingestion of nitrate in drinking water and risk of specific cancers or adverse reproductive outcomes among potentially susceptible subgroups likely to have elevated endogenous nitrosation. Positive associations have been observed for some but not all health outcomes evaluated. Second, the epidemiologic studies of cancer do not support an association between ingestion of dietary nitrate (vegetables) and an increased risk of cancer, because intake of dietary nitrate is associated with intake of antioxidants and other beneficial phytochemicals. Third, 2–3 % of the population in Western Europe and the US could be exposed to nitrate levels in drinking water exceeding the WHO standard of 50 mg/l nitrate, particularly those living in rural areas. The health losses due to this exposure cannot be estimated. Therefore, we conclude that it is not possible to weigh the costs and benefits from changing the nitrate standard for drinking water and groundwater resources by considering the potential consequences for human health and by considering the potential savings due to reduced costs for nitrate removal and prevention of nitrate pollution.     

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.     

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.     

Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies

Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in each study. During 6-20 years of follow-up between 1980 and 2003, 7,885 incident cases of colorectal cancer were diagnosed among 702,647 participants. The authors calculated study-specific multivariate relative risks and then combined them using a random-effects model. In general, intakes of specific carotenoids were not associated with colorectal cancer risk. The pooled multivariate relative risks of colorectal cancer comparing the highest quintile of intake with the lowest ranged from 0.92 for lutein + zeaxanthin to 1.04 for lycopene; only for lutein + zeaxanthin intake was the result borderline statistically significant (95% confidence interval: 0.84, 1.00). The associations observed were generally similar across studies, for both sexes, and for colon cancer and rectal cancer. These pooled data did not suggest that carotenoids play an important role in the etiology of colorectal cancer.     

A Case-Control Study of Nitrate in Drinking Water and Non-Hodgkin's Lymphoma in Minnesota

Nitrate in drinking water has been implicated as a possible risk factor for non-Hodgkin's lymphoma. The authors examined the association between non-Hodgkin's lymphoma and waterborne nitrate through a population-based case-control study of white men in Minnesota. The authors, by linking residential histories with community water records, estimated average long-term exposure to nitrate in drinking water from 1947 to 1975 for 73 cases diagnosed between 1980 and 1982 and for 147 controls who used community water supplies. No association was found between nitrate levels in community water supplies and non-Hodgkin's lymphoma within the range of study exposures (median of highest exposure category = 2.4 mg nitrate/l [range = 0.1-7.2 mg/l]). The findings provide some safety assurance for those who use water systems that have nitrate levels that are less than 2.4 mg/l.