RESUMO
Urinary excretion levels of nitrate and N-nitrosoproline were determined in 160 individuals in a Colombian population at high risk for gastric cancer. In 156 of these subjects urinary levels of 3-methyladenine and 7-methylguanine were determined. Gastric biopsy specimens were obtained from 118 individuals and were histologically characterized according to pathological criteria into the following groups: normal, superficial gastritis, chronic atrophic gastritis, chronic atrophic gastritis with intestinal metaplasia, and dysplastic. The histological changes were correlated with the four variables listed above. There were no significant differences in the excretion of nitrate, N-nitrosoproline, 3-methyladenine, or 7-methylguanine in subjects with different pathological changes. A statistically significant correlation was present between nitrate and N-nitrosoproline excretion in the total population group (r = 0.297, P = 0.0001). A highly significant correlation (r = 0.56, P = 0.0002) was noted for urinary nitrate and N-nitrosoproline excretion in individuals with intestinal metaplasia and dysplasia. An increase in the urinary excretion of 3-methyladenine and 7-methylguanine was associated with tobacco smoking in the total population group.
Assuntos
Adenina/análogos & derivados , Guanina/análogos & derivados , Nitratos/urina , Nitrosaminas/urina , Neoplasias Gástricas/urina , Adenina/urina , Colômbia , Guanina/urina , Humanos , Análise de Regressão , Fatores de RiscoRESUMO
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.
Assuntos
Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Atrofia , Doença Crônica , Colômbia , Mucosa Gástrica/patologia , Gastrite/patologia , Humanos , Metaplasia , Músculo Liso/patologia , Lesões Pré-Cancerosas/epidemiologia , Fatores de Risco , Estômago/patologia , Neoplasias Gástricas/epidemiologiaRESUMO
In an attempt to characterize the natural history of the gastric precancerous process, 1422 residents of a high risk area of Nariño, Columbia, have been followed from 3-16 years (average 5.1) with repeated gastric biopsies, for a total of 7290 person-years. The original cohort consisted of 1788 individuals yielding a successful completion rate of 79.5%. Comparison of initial and subsequent biopsies revealed a very complex dynamic flow of both progressive and regressive events, suggesting sporadic environmental forces of modulation. One-time measurement of gastric juice, pH, and nitrite failed to predict future events in the gastric mucosa. The net loss of individuals whose gastric mucosa initially showed normal histology or superficial gastritis was 3.3%/year, representing a net gain of 1.7% for chronic atrophic gastritis, 0.9% for intestinal metaplasia, and 0.7% for dysplasia. The incidence rate of gastric cancer in this population was 0.16/100 person-years. The net rates of progression were higher and those of regression lower in older compared to younger individuals. The general pattern detected is that of a slow forward movement in the previously described hierarchical organization of precursor lesions. The presence of progressive as well as regressive changes and the slow pace of change offer special opportunities to inhibit progression through intervention strategies targeting previously identified etiological factors. The difficulties and opportunities offered by the long term follow-up studies as well as the congruency of the findings with current etiological hypotheses are discussed.
Assuntos
Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Atrofia , Biópsia , Estudos de Coortes , Colômbia , Seguimentos , Mucosa Gástrica/patologia , Humanos , Metaplasia , Músculo Liso/patologia , Lesões Pré-Cancerosas/epidemiologia , Fatores de Risco , Estômago/patologia , Neoplasias Gástricas/epidemiologiaRESUMO
Human gastric juice samples were investigated from high- and low-risk areas (Colombia and Boston) for factors which influence the stability of nitrite and its potential for nitrosamine formation. The samples from individuals with chronic atrophic gastritis and intestinal metaplasia were not reactive to nitrite and supported a rate of nitrosation largely compatible with the nitrite and thiocyanate concentration. The samples from other individuals contained factors which destroyed nitrite and inhibited nitrosation. There were several samples from both groups which had an elevated rate of nitrosation catalyzed by unknown factors. It is suggested that continued hypochlorhydria might deplete gastric juice of its natural protective factors and lead to an elevated risk of gastric cancer in agreement with our earlier etiological model [1].
Assuntos
Suco Gástrico/metabolismo , Gastrite Atrófica/metabolismo , Gastrite/metabolismo , Nitritos/metabolismo , Nitrosaminas/metabolismo , Colômbia , Humanos , Massachusetts , Nitratos/metabolismo , Risco , Tiocianatos/metabolismoRESUMO
Nitrohexane has been identified as a major product formed following treatment of corn (Zea mays) with nitrous acid. Preliminary evidence suggests that another compound isolated from the nitrosated corn is an unsaturated nitrolic acid. As an aid to the analysis of N-nitro compounds, we have characterized the response of a chemiluminescence detector (Thermal Energy Analyzer) as a function of pyrolysis chamber temperature for several nitrosamines and for an aliphatic C-nitroso compound, an aromatic C-nitro compound, a nitramine and an alkyl nitrite. The response-temperature profiles are valuable in distinguishing among the various compounds and in optimizing the sensitivity of the detector for use in chromatography. Other tests, including photolysis and stability toward nitrite-scavenging reagents, further aid in distinguishing among the various compounds.
Assuntos
Nitritos , Compostos Nitrosos/análise , Ácido Nitroso , Zea mays , Cromatografia Gasosa , Colômbia , Hexanos/análise , Massachusetts , Nitrocompostos/análise , Nitrosaminas/análise , Neoplasias Gástricas/induzido quimicamente , Zea mays/análiseRESUMO
The gastric juice of patients with atrophic gastritis from the high-risk gastric cancer region of Nariño, Colombia, was analyzed for nitrate, nitrite, and thiocyanate content. Patients whose gastric juice pH is greater than 5 have significant elevation of nitrite values. The possible role of nitrite in gastric carcinogenesis is discussed.
Assuntos
Suco Gástrico/análise , Lesões Pré-Cancerosas/análise , Neoplasias Gástricas/análise , Adulto , Idoso , Colômbia , Feminino , Gastrite/complicações , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Nitratos/análise , Nitritos/análise , Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologiaRESUMO
Samples of gastric contents from 2 groups of patients from a region of high risk for gastric cancer were analyzed for pH, nitrite, nitrate, thiocyanate, and chloride. In each group, the patients could be divided into 2 subgroups: those with a gastric pH of less than 5 and those with a gastric pH of greater than 5. Above pH 5, nitrite was correlated with nitrate. The pH greater than 5 subgroups had significantly higher (P less than 0.01) nitrite content (20- to 100-fold). Some high- and low-nitrite samples were also analyzed for macro and trace metal ions, but differences were not significant. This is the first report in which patients with diagnosed gastric pathology related to a precancerous state were shown to have high levels of a putative carcinogen precursor. The results were compatible with our original hypothesis of intragastric nitrite formation by bacterial reduction of nitrate and concomitant synthesis of carcinogenic N-nitroso compounds.
Assuntos
Suco Gástrico/análise , Nitritos/análise , Neoplasias Gástricas/etiologia , Idoso , Cloretos/análise , Colômbia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Nitratos/análise , Lesões Pré-Cancerosas/análise , Risco , Neoplasias Gástricas/análise , Tiocianatos/análiseRESUMO
A case control study of patients discharged from hospitals revealed fourfold differences in geographic variation in stomach cancer risk within the Department of Narino (Colombia). Data from gastroscopic surveys of population groups, samples of water supplies, and urine and saliva in Narino also indicated a generally positive correlation among the following parameters: 1) gastric cancer risk, 2) prevalence of chronic atrophic gastritis and intestinal metaplasia, 3) nitrate content of well waters, and 4) nitrate excretion by the population. Urinary excretion reflected the ingestion of nitrates, and this implied a higher average intake of nitrates in the populations at high risk for stomach cancer. The Narino data could be construed as presumptive epidemiologic evidence for the role of nitrate availability in the etiology of stomach cancer.