Abstract  #We questioned mothers of 209 young brain tumor patients and mothers of 209 controls about experiences of possible etiological relevance which they had during pregnancy or which their children had while growing up. Long-suspected brain tumor risk factors such as head trauma and X-rays appeared to be factors for relatively few cases. Increased risk was associated with maternal contact with nitrosamine-containing substances such as burning incense (odds ratio, 3.3; p = 0.005), sidestream cigarette smoke (odds ratio, 1.5; p = 0.03), and face makeup (odds ratio, 1.6; p = 0.02); with maternal use of diuretics (odds ratio, 2.0; p = 0.03) and antihistamines (odds ratio, 3.4; p = 0.002); and with the level of maternal consumption of cured meats (p = 0.008). These drugs contain nitrosatable amines and amides, and the cured meats contain nitrites, chemicals which are precursors of N-nitroso compounds. We propose a hypothesis that brain tumors in these young people are related to in utero exposure to N-nitroso compounds and their precursors, the most potent nervous system carcinogens known in experimental animals.

Abstract  This study assessed whether there is any variation in the incidence of haematological malignancies between geographical areas of differing water supplies in the South West peninsula of the United Kingdom (1984 to 1988 inclusive). The possibility of correlations existing between variation in water quality and variation in the incidence of haematological malignancies was examined. Haematological incidence data, taken from the Leukaemia Research Fund's Data Collection Study, were mapped into 46 geographical areas of differing water supply. The distribution of the mapped cases was then tested for homogeneity using the Potthoff and Whittinghill (1966) test score. The age-adjusted incidence ratios calculated during the heterogeneity testing were examined for correlations with water quality indicators using correlation and stepwise regression. Significant heterogeneity in the incidence rates among water supply areas was observed for two groups of disease-acute leukaemias and myeloproliferative disorders. Three water quality indicators-pH, nitrate concentration and aluminium concentration-varied considerably over the study period. Significant correlations were observed between the standardized incidence ratios of five disease categories and some water quality indicators, especially aluminium and trihalomethane concentrations. The standardized incidence ratios of some haematological malignancies differed between geographical areas of water supply in South West England, and the evidence suggests that this variation may be associated with variation in water quality indicators. Although this lends support to similar findings in the United States of America, the pattern of correlations are affected by disease latency and statistical methodology.

Abstract  Several possible risk factors for brain tumors have been suggested in the past, including N-nitroso compounds, but with the exception of ionizing radiation, none has been consistently confirmed. The present study was aimed at assessing the influence of nutritional factors, including N-nitroso compounds, in the etiology of brain tumors, specifically gliomas and meningiomas. One hundred and thirty-nine cases with confirmed brain tumors diagnosed between 1987 and 1991 in central Israel and 278 controls matched according to age, sex, and ethnic origin were interviewed. Nutritional data were obtained using a semiquantitative food frequency approach. A significant positive association for both types of brain tumors was found with high protein intake (odds ratio (OR) = 1.94, 95% confidence interval (CI) 1.03-3.63), while intake of sodium was inversely related to both types of brain tumors (OR = 0.52, 95% CI 0.31-0.87). Increased consumption of total fat and cholesterol was inversely related to gliomas (high intake of fat: OR = 0.45, 95% CI 0.20-1.07; high intake of cholesterol: OR = 0.38, 95% CI 0.14-1.01). However, neither fat intake nor cholesterol intake was significantly related to the risk of meningiomas. Although N-nitroso compounds were not found to be directly associated with brain tumors, the data suggested the presence of an interaction between the effects of N-nitroso compounds and protein intake and between N-nitroso compounds and cholesterol intake. The data suggest that dietary factors may play an important, though yet undefined, role in the development of brain tumors.

Abstract  In order to detect possible formation of carcinogenic N-nitroso compounds from nitrite and nitrosatable compounds in meat, studies were carried out with 70 male and 140 female F0 rats, divided into six groups, and 60, 100, 70, 60, 60 and 66 of their male and female offspring. One control group received casein and other groups chopped pork as the sole protein source (45%, mass/mass) on a fresh basis, either salted (sodium chloride) or not. For test groups, nitrite was also added to the meat before autoclaving and storing the diet and represented mass fractions of 200, 1 000 and 4 000 mg/kg, as sodium nitrite. The results do not demonstrate any effect on reproduction and no significant carcinogenic effect was revealed. However, an observed tendency toward an increased number of tumour-bearing rats in the highest dose group, plus the possible formation of carcinogenic N-nitroso compounds in nitrite-treated meat products, led to a recommendation to reduce the use of nitrite. Results from a concomitant study demonstrate that it is possible to produce many cured-meat products with the addition of only 50 mg/kg nitrite.

Abstract  Incidence rates for adenocarcinoma of the esophagus and gastric cardia have been rising rapidly. We examined nutrient intake as a risk factor for esophageal and gastric cancers in a population-based case-control study in Connecticut, New Jersey, and western Washington state. Interviews were completed for cases with histologically confirmed esophageal adenocarcinoma (n = 282), adenocarcinoma of the gastric cardia (n = 255), esophageal squamous cell carcinoma (n = 206), and noncardia gastric adenocarcinoma (n = 352), along with population controls (n = 687). Associations between nutrient intake and risk of cancer were estimated by adjusted odds ratios (ORs), comparing the 75th versus the 25th percentile of intake. The following nutrients were significantly inversely associated with risk of all four tumor types: fiber, beta-carotene, folate, and vitamins C and B6. In contrast, dietary cholesterol, animal protein, and vitamin B12 were significantly positively associated with risk of all four tumor types. Dietary fat [OR, 2.18; 95% confidence interval (CI), 1.27-3.76] was significantly associated with risk of esophageal adenocarcinoma only. Dietary nitrite (OR, 1.65; 95% CI, 1.26-2.16) was associated with noncardia gastric cancer only. Vitamin C supplement use was associated with a significantly lower risk for noncardia gastric cancer (OR, 0.60; 95% CI, 0.41-0.88). Higher intake of nutrients found primarily in plant-based foods was associated with a reduced risk of adenocarcinomas of the esophagus and gastric cardia, whereas higher intake of nutrients found primarily in foods of animal origin was associated with an increased risk.

Abstract  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.

Abstract  Carcinogenic risk of small doses of precursors of nitroso compounds, i.e. sodium nitrite (total dose in 0.2-2.0 g/mouse in drinking water) and morpholine (total dose is 0.23 g/mouse in bread) was studied in 520 CBA and 290 C57Bl mice during 96 weeks. It is shown that under these conditions the carcinogenic effect was more pronounced in CBA mice: there was a significant increase in general incidence of tumours, particularly liver tumours and hemoblastoses in CBA females and malignant liver tumours in CBA males.

Abstract  The effects of long-term concurrent administration of powdered fish meal and sodium nitrite were examined in F344 rats. A total of 600, 6-week-old rats were divided into 6 male and 6 female groups, each consisting of 50 animals. Rats in groups 1-3 and 7-9 were respectively fed diets supplemented with 64%, 32% and 8% (basal diet) fish meal, and simultaneously given 0.12% sodium nitrite in their drinking water. Groups 4-6 and 10-12 were respectively given 64%, 32% and 8% fish meal and tap water. At the 104th week, all surviving animals were killed and examined histopathologically, Treatment with fish meal dose-dependently increased the incidences and multiplicities of atypical tubules, adenomas and renal cell carcinomas in sodium nitrite-treated males. Females were less susceptible than males for renal tumor induction. In males given the 64% fish meal diet alone, the incidence and multiplicity of atypical tubules were also significantly increased as compared with the 8% fish meal alone case. Nephropathy was apparent in fish meal-treated groups in a clear dose-dependent manner, irrespective of the sodium nitrite treatment, and was more prominent in males than in females. Dimethylnitrosamine was found in the stomach contents after 4-week treatment with 64% fish meal plus 0.12% sodium nitrite, at a level twice that in the 8% fish meal plus 0.12% sodium nitrite group. The results clearly indicate that concurrent administration of fish meal and sodium nitrite induces renal epithelial tumors. Further studies are required to elucidate how nephropathy and nitrosamines produced in stomach contents may contribute to the observed renal tumor induction.

Abstract  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 (<median) vitamin C intake compared with those who had low water nitrate and high vitamin C intake.

Conclusions. Our data suggest that long-term exposure to nitrate in drinking water at levels in this study (90th percentile 5.5 mg/liter nitrate-nitrogen) is not associated with risk of bladder cancer.

Abstract  A case-control study on diet and gastric cancer, carried out in selected areas of four regions of Spain (Aragon, Castile, Catalonia, and Galicia) in 1988 and 1989, included 354 cases of histologically confirmed gastric adenocarcinoma and 354 controls matched by age, sex, and area of residence. Cases and controls were selected from 15 hospitals, representing most of the hospital facilities in the study areas. Usual diet was estimated by means of a dietary history questionnaire administered by interview. An increased risk of gastric cancer was observed for high consumption of exogeneous nitrosamines (odds ration = 2.1 for the highest quartile of consumption versus the lowest; p for linear trend = 0.007), nitrites, fat, and cholesterol. However, in a multivariate regression model, the effect of fat and cholesterol disappeared. An inverse association with the risk for gastric cancer was seen for high intake of fiber, vitamin C, folate, carotene, and nitrates. High consumption of vitamin C seemed to neutralize the increased risk related to simultaneous consumption of nitrosamines. For histologic type, the authors found no meaningful differences in the effect of most of the nutrients between intestinal and diffuse cancers. Their findings are consistent with previously reported results about the protective effect of fruit and vegetables and the increased risk associated with foods that are important sources of nitrites and preformed nitrosamines.

Abstract  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. Long-term consumption of community water with average nitrate levels in the highest quartile (greater than or equal to 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 greater than or equal to 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 long-term exposure to elevated nitrate levels in drinking water may contribute to the risk of NHL.

Abstract  The carcinogenic activity of endogenously synthesized N-nitroso-bis(2-hydroxy-propyl)amine (NDHPA) was investigated in male Wistar rats administered bis(2-hydroxypropyl)amine (DHPA), mixed into a powdered diet at a concentration of 1%, and NaNO2 dissolved in distilled water at concentrations of 0.15% and 0.3%, for 94 weeks. Urinary excretion of NDHPA clearly demonstrated its endogenous synthesis in rats given 1% DHPA and 0.3% NaNO2, but not in the groups receiving either of these precursors alone. Tumours of the nasal cavity, lung, oesophagus, liver and urinary bladder were found in rats treated with 1% DHPA and 0.15% or 0.3% NaNO2. The incidences of nasal cavity and lung tumours reached 74% and 58% respectively, in rats given 1% DHPA and 0.3% NaNO2. The tumour distribution was almost the same as that seen in rats given NDHPA. These results indicate that endogenously synthesized NDHPA has similar carcinogenic activity to exogenously administered NDHPA in rats.

Abstract  Long-term feeding studies were conducted in Sprague-Dawley rats and Syrian golden hamsters using various dietary concentrations of nitrite and morpholine (up to 1000 ppm of each) or N-nitrosomorpholine (5 or 50 ppm). Most combinations of the two chemicals induced a high incidence of hepatocellular carcinoma in rats and a lower incidence in hamsters. The highest level of nitrite and morpholine (1000 ppm of each) had a stronger potential for carcinogenesis in both rats and hamsters than did a dietary level of 50 ppm of preformed N-nitrosomorpholine. Nitrite and morpholine also induced angiosarcomas in both species, most frequently in the liver, with the lung as the next most common site. The nitrite concentration in the diet seemed to have a greater effect on the incidence of hepatocellular carcinoma and angiosarcoma in the rat than did the concentration of morpholine. Dietary concentrations of 5 ppm each of nitrite and morpholine induced hepatocellular carcinoma and angiosarcoma in some rats. High concentrations of sodium nitrite alone were associated with a relatively high incidence of lymphoreticular tumours.

Abstract  A population-based case-control study of gastric cancer was conducted in areas with contrasting incidence rates in Sweden. Face-to-face interviews were carried out with 338 (74.1%) of all eligible cases and 679 (77.3%) of the selected controls. Consumption of selected nutrients during adolescence and 20 years prior to interview was estimated, together with life-time intake of vitamin supplements. Ascorbic acid and beta-carotene had an unequivocal protective effect, but alpha-tocopherol and nitrate were also negatively associated with gastric-cancer risk. In a multivariate analysis including all of these factors, only ascorbic acid remained a significant protective factor. The only macronutrient positively associated with the risk of gastric cancer was fat: intake 20 years prior to interview, but not during adolescence, was found to have a significant impact. Supplementation with vitamins almost halved the risk after adjustment for dietary intake of the corresponding vitamins. While the protective effect of vitamin C and beta-carotene could conceivably be ascribed to other agents in the diet, the strong negative association between supplementation with vitamin C and risk of gastric cancer supports the hypothesis of a protective role of this anti-oxidant.

Abstract  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.

Abstract  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.

Abstract  A mixture of 0·1% disulfiram together with 0·2% sodium nitrite in powdered rat diet was fed to 20 male and 20 female Fischer 344 rats for 78 wk, after which the animals were observed until death. Ten of the males and 12 of the females died with tumours of the oesophagus, tongue, squamous stomach and nasal cavity. None of these tumours was observed in rats fed either disulfiram or sodium nitrite alone at similar doses. The tumours were attributed to the reaction of disulfiram and nitrite in the stomach, with the formation of nitrosodiethylamine, which has given rise to these tumours in Fischer rats from the same colony.

Abstract  Nitrate and nitrite were measured in the saliva of two populations who differed in their risk of developing gastric cancer. Surprisingly, the levels of both ions were significantly higher in the low-risk group.

Abstract  A population based case-control study was conducted in upstate New York to investigate the effects of maternal diet, smoking, and alcohol consumption, prior to and during pregnancy, on risk of childhood brain tumors (CBT). Of particular interest were factors known to contain nitrosamines or their precursors, nitrites and nitrates. The NY State Cancer Registry was used as the primary source for identifying eligible cases. CBT cases underwent pathologic review and, in the absence of histologic data, a neurosurgeon reviewed clinical and laboratory reports to confirm the diagnosis. Two controls, matched on year of birth, gender and race were selected for each case from birth certificate files. 338 cases and 676 controls were included in the study. Risk factor data, including familial history of CBT, were collected through telephone interviews with mothers of study subjects. Conditional logistic regression analysis was employed to adjust for matched variables and control for potential confounding factors. Statistically significant associations were observed for consumption of hot dogs and other cured meats during pregnancy. The odds ratio for hot dog consumption once per week compared to less often was 1.33 with a 95% confidence interval (CI) of 1.00-1.76. Consumption of hot dogs 2-3 times per week conferred greater risk (OR = 2.01, 95% CI: 1.10-3.65). Maternal consumption during pregnancy of "other" cured meats once a week increased risk of CBT six-fold (OR = 6.04, 95% CI: 1.89-19.31). No significant associations were found for coffee and/or tea consumption or cigarette smoking. Drinking wine during pregnancy was found to be negatively associated with CBT (OR = 0.53, 95% CI: 0.33-0.84). Analyses were also conducted by histologic type of CBT. The present study served to test the hypothesis that exposure to nitrosamines during pregnancy effects the development of CBT. (Abstract from Toxline)

Abstract  Three groups of 24 male, and three groups of 24 female F344 rats were fed sodium nitrite for 2 years. Two male and two female groups received 2000 parts per million sodium nitrite mixed with powdered food. The remaining pair of groups received 2000 parts per million in drinking water at the rate of 100 ml per week. A similar pair of groups of untreated animals were maintained as controls. There was little difference in survival between the treated groups and the controls. The incidence of liver neoplasms, which were carcinomas and neoplastic nodules, in the two groups of females treated with sodium nitrite in feed was significantly higher than in the controls, but there was no significant difference in the males. The incidence of monocytic leukemia for each of the nitrite-treated groups was always lower than that for the matching untreated control groups, with the difference attaining or approaching significance in five of the six cases.

Abstract  The first and second editions of the WHO Guidelines for Drinking-water Quality were used by developing and developed countries worldwide as the basis for regulation and standard setting to ensure the safety of drinking-water. They recognized the priority that should be given to ensuring microbial safety and provided guideline values for a large number of chemical hazards. It describes a “Framework for Drinking-water Safety” and discusses the roles and responsibilities of different stakeholders, including the complementary roles of national regulators, suppliers, communities and independent “surveillance” agencies. Developments in this edition of the Guidelines include significantly expanded guidance on ensuring the microbial safety of drinking-water — in particular through comprehensive system-specific “water safety plans”. Information on many chemicals has been revised to account for new scientific information and information on chemicals not previously considered has been included. For the first time, reviews of many waterborne pathogens are provided. Recognizing the need for different tools and approaches in supporting large and community supplies, this edition continues to describe the principal characteristics of the approaches to each. New sections deal with the application of the Guidelines to specific circumstances, such as emergencies and disasters, large buildings, packaged/bottled water, travellers, desalination systems, food production and processing and water safety on ships and in aviation.

Abstract  The gastric precancerous process is evaluated in 1788 participants in a gastroscopy survey in the population of Nariño, Colombia, which has one of the highest gastric cancer incidence rates on record. A detailed histological classification is used, and a hierarchical distribution of lesions is described with the main stages being gland neck hyperplasia, atrophy (gland loss), intestinal metaplasia and dysplasia. Acute inflammation was not found to be a specific stage in the sequence but rather a common finding in all stages of the precancerous spectrum. Indices of disease progression for the different steps are calculated and found to increase with gastric pH and nitrate and nitrite content of the gastric juice. The effects of high pH and nitrite content are intimately correlated. Relative risks of specific lesions, namely, hyperplasia, atrophy, metaplasia, and dysplasia, increase linearly with higher pH, nitrate, and nitrite values in the gastric juice. The severity of atrophy correlates with the prevalence of metaplasia, suggesting a sequential relationship between the described stages, a finding supported by all parameters examined. The model of progression described may serve as a basis for comparisons with populations at different levels of gastric cancer risk but it fails to provide information concerning the time required for each change, which should be provided by follow-up (cohort) studies.

Abstract  BACKGROUND: It has been hypothesized that a high dietary intake of nitrosamines and their precursors, nitrites and nitrates, is a risk factor for brain tumors. Vitamins C and E inhibit the formation of nitrosamines and thus may be protective.

METHODS: We conducted a case-control study of maternal diet and the risk of primitive neuroectodermal tumors of the brain in children. The case patients were under the age of six years at diagnosis in 1986 to 1989. The controls were selected by random-digit telephone dialing and were matched for age and race to 166 case patients. Telephone interviews with the mothers included questions on the frequency of consumption of alcohol, vitamin and mineral supplements, and 53 foods during pregnancy.

RESULTS: Significant protective trends were observed for vegetables (odds ratio for the highest quartile group for intake relative to the lowest, 0.37; P for trend = 0.005), fruits and fruit juices (odds ratio, 0.28; P = 0.003), vitamin A (odds ratio, 0.59; P = 0.03), vitamin C (odds ratio, 0.42; P = 0.009), nitrate (odds ratio, 0.44; P = 0.002), and folate (odds ratio, 0.38; P = 0.005). A nonsignificant trend of increasing risk was observed for nitrosamine (odds ratio, 1.65; P = 0.15). The use of iron (odds ratio, 0.43; P = 0.004), calcium (odds ratio, 0.42; P = 0.05), and vitamin C (odds ratio, 0.35; P = 0.04) supplements at any time during the pregnancy and the use of multivitamins during the first six weeks (odds ratio, 0.56; P = 0.02) were associated with decreased risk. In multivariate analyses, folate, early multivitamin use, and iron supplements generally remained protective.

CONCLUSIONS: These results do not support the hypothesis that nitrosamines have a role in the development of primitive neuroectodermal tumors in young children, but they do suggest that certain other aspects of maternal diet can influence the risk.