Abstract  Effects of simultaneous treatment with NaNO2 and butylated hydroxyanisole, catechol, or 3-methoxycatechol were examined in a rat multiorgan carcinogenesis model. Groups of 15 animals were given a single i.p. injection of 100 mg/kg of body weight diethylnitrosamine, 4 i.p. injections of 20 mg/kg of body weight N-methylnitrosourea, 4 s.c. injections of 40 mg/kg of body weight dimethylhydrazine, p.o. treatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for the first 2 weeks and p.o. treatment with 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine in the drinking water for the next 2 weeks of the initial 4-week initiation period. Starting 3 days after the completion of these carcinogen treatments, animals were given diets containing 2% butylated hydroxyanisole, 0.8% catechol, 2% 3-methoxycatechol, or basal diet either alone or in combination with 0.3% sodium nitrite until week 28, when complete autopsy was performed. Histological examination showed that NaNO2 strongly enhanced development of forestomach lesions but inhibited that of glandular stomach lesions in rats simultaneously given catechol or 3-methoxycatechol with or without prior carcinogen exposure. 3-Methoxycatechol promoted esophageal carcinogenesis either with or without NaNO2, but promoting effects of catechol were evident only in the presence of NaNO2. In addition, treatment with NaNO2 after carcinogen exposure enhanced forestomach carcinogenesis. These results indicate that NaNO2 can modify phenolic antioxidant-induced cell proliferation and/or carcinogenesis, particularly in the upper digestive tract.

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  #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  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  A case-control study investigating risk factors for childhood brain tumors was conducted in the Ile de France (Paris region). During a 2-year period (1985-1987) 109 newly diagnosed cases were identified and, of these, 75 could be interviewed. In the same region, 113 population controls, frequency-matched for year of birth, were interviewed. Odds ratios adjusted for child's age and sex and for maternal age were estimated for each risk factor present in utero or during childhood by conditional logistic regression. Statistically significant associations were found for the following risk factors: farm residence, cat scratches, home treated with pesticides, passive smoking, family history of cancer, antihistamine intake. Intake of vitamin supplements during childhood was associated with a decrease in risk. This study is part of a multicentric case-control study coordinated by the International Agency for Research on Cancer and its results will be compared for consistency, and pooled with those of other centers using the same protocol.

Abstract  Overnight urine samples were collected from approximately 60 male adults in each of 69 counties of China in 1989. Two specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids and nitrate were measured in urine samples and correlated with cumulative mortality rates for subjects aged between 0 and 64 years in the 1970s. Oesophageal cancer mortality rates were positively and significantly associated with (i) urinary levels of excreted N-nitrosoproline (NPRO) (after proline and ascorbic acid loading or proline loading only), (ii) N-nitrososarcosine levels, and (iii) nitrosation potential (the decrease in the amount of urinary NPRO after adding ascorbic acid to the proline load). There were also positive correlations between the urinary level of NPRO or other N-nitrosamino acids and that of nitrate. The urinary excretion of nitrate was associated with consumption of various nitrate-rich vegetables. The results suggest that N-nitroso compounds (NOC) or other nitrite-derived carcinogens are implicated in the aetiology of oesophageal cancer in China.

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  The intensity of the abnormal electron spin resonance signal previously observed in the livers of rats which were fed various chemical carcinogens is found to depend on the intake of the carcinogen, protein, and nitrate or nitrite. Nitrite enhances the intensity of the abnormal electron spin resonance signal and inhibits the carcinogenicity of 2-acetyl-aminofluorene. The appearance of the signal-bearing complex and the possible mechanism of its anticarcinogenic activity are discussed.

Abstract  N-nitroso compounds are carcinogens that can be ingested directly or synthesized from nitrites and nitrates. The possible role of N-nitroso compounds in the induction of upper aerodigestive tract tumours was considered in a case-control study conducted in the Valle d'Aosta, an Italian region with a high incidence of these neoplasms. Nitrate, nitrite, labile and stable N-nitroso compounds were analysed in the saliva of 36 patients with cancers of the upper aerodigestive tract and 23 healthy individuals. After allowing for tobacco, salivary nitrate, nitrite and N-nitroso compounds were not associated with an increased risk of upper aerodigestive tract cancers. The odds ratio for continuous units of total N-nitros compounds was 0.99 (95% confidence interval 0.9-1.1). Thus, salivary nitrate, nitrite and N-nitroso compounds might not be suitable markers for the assessment of the risk of cancer of the upper aerodigestive tract, although a role for N-nitroso compounds cannot be excluded.

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 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  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  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  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  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  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  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.

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  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.