Association between exposure to air pollutants and hospitalization for SARS-Cov-2: an ecological time-series study

ABSTRACT BACKGROUND: Exposure to air pollutants and illness by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection can cause serious pulmonary impairment. OBJECTIVE: To identify a possible association between exposure to air pollutants and hospitalizations due to SARS-Cov-2. DESIGN AND SETTING: Ecological time-series study carried out in Taubaté, Tremembé, and Pindamonhangaba in 2020 and 2021. METHODS: Study with Sars-Cov-2 hospitalizations with information on hospitalization date, sex and age of the subjects, duration of hospitalization, type of discharge, and costs of these hospitalizations. Statistical analysis was performed through a negative binomial regression, with data on pollutant concentrations, temperature, air relative humidity, and hospitalization date. Coefficients obtained by the analysis were transformed into relative risk for hospitalization, which estimated hospitalizations excess according to an increase in pollutant concentrations. RESULTS: There were 1,300 hospitalizations and 368 deaths, with a predominance of men (61.7%). These data represent an incidence rate of 250.4 per 100,000 inhabitants and 28.4% hospital lethality. Significant exposure (P value < 0.05) occurred seven days before hospital admission (lag 7) for nitrogen dioxide (NO2) (relative risk, RR = 1.0124) and two days before hospital admission for PM2.5 (RR = 1.0216). A 10 μg/m3 in NO2 concentration would decrease by 320 hospitalizations and ¼ US $ 240,000 in costs; a 5 μg/m3 in PM2.5 concentration would decrease by 278 hospitalizations and ¼ US $ 190,000 in costs. CONCLUSION: An association between exposure to air pollutants and hospital admission due to Sars-Cov-2 was observed with excess hospitalization and costs for the Brazilian public health system.

Association between exposure to air pollutants and hospitalization for SARS-Cov-2: an ecological time-series study.

BACKGROUND: Exposure to air pollutants and illness by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection can cause serious pulmonary impairment. OBJECTIVE: To identify a possible association between exposure to air pollutants and hospitalizations due to SARS-Cov-2. DESIGN AND SETTING: Ecological time-series study carried out in Taubaté, Tremembé, and Pindamonhangaba in 2020 and 2021. METHODS: Study with Sars-Cov-2 hospitalizations with information on hospitalization date, sex and age of the subjects, duration of hospitalization, type of discharge, and costs of these hospitalizations. Statistical analysis was performed through a negative binomial regression, with data on pollutant concentrations, temperature, air relative humidity, and hospitalization date. Coefficients obtained by the analysis were transformed into relative risk for hospitalization, which estimated hospitalizations excess according to an increase in pollutant concentrations. RESULTS: There were 1,300 hospitalizations and 368 deaths, with a predominance of men (61.7%). These data represent an incidence rate of 250.4 per 100,000 inhabitants and 28.4% hospital lethality. Significant exposure (P value < 0.05) occurred seven days before hospital admission (lag 7) for nitrogen dioxide (NO2) (relative risk, RR = 1.0124) and two days before hospital admission for PM2.5 (RR = 1.0216). A 10 µg/m3 in NO2 concentration would decrease by 320 hospitalizations and ¼ US $ 240,000 in costs; a 5 µg/m3 in PM2.5 concentration would decrease by 278 hospitalizations and ¼ US $ 190,000 in costs. CONCLUSION: An association between exposure to air pollutants and hospital admission due to Sars-Cov-2 was observed with excess hospitalization and costs for the Brazilian public health system.

Fine particulate matter and ischemic heart diseases inrelation to sex. An ecological time series study.

BACKGROUND: Exposure to some air pollutants is associated with cardiovascular diseases. The objective of this study was to quantify the effect of exposure to fine particulate matter in hospitalizations due to ischemic heart disease and the costs to the healthcare system. DESIGN AND SETTING: Time-series ecological study conducted in Taubaté, Brazil. METHODS: Data on hospitalizations due to ischemic heart diseases (ICD I-20 to I-24) in the municipality of Taubaté (SP), Brazil, among adults of both sexes aged 40 years and over, from August 2011 to July 2012, were obtained from DATASUS. Fine particulate matter (PM2.5) concentrations were estimated from a mathematical model. Poisson regression was used in statistical analyses to estimate the relative risks of exposure to PM2.5 for both sexes and after stratification according to sex. The excess of hospitalizations and consequent excess expenditure for the healthcare system were calculated. RESULTS: There were 1040 admissions, among which 382 had ischemic heart diseases (257 males). Themean PM2.5 concentration was 13.2 µg/m3 (SD = 5.6). Significant effects from exposure were noted 4and 5 days after exposure (lag 4 and lag 5) for both sexes and for male sex; for female sex, the effect was 2 days after exposure (lag 2). There were 59 excess hospitalizations for an increase in PM2.5 concentration of 5 µg/m3 and excess expenditure of US$ 150,000 for the National Health System. CONCLUSIONS: An excess of hospital admissions due to ischemic heart disease, with excess expenditure, was identified consequent to PM2.5 exposure.

Fine particulate matter and ischemic heart diseases inrelation to sex. An ecological time series study

ABSTRACT BACKGROUND: Exposure to some air pollutants is associated with cardiovascular diseases. The objective of this study was to quantify the effect of exposure to fine particulate matter in hospitalizations due to ischemic heart disease and the costs to the healthcare system. DESIGN AND SETTING: Time-series ecological study conducted in Taubaté, Brazil. METHODS: Data on hospitalizations due to ischemic heart diseases (ICD I-20 to I-24) in the municipality of Taubaté (SP), Brazil, among adults of both sexes aged 40 years and over, from August 2011 to July 2012, were obtained from DATASUS. Fine particulate matter (PM2.5) concentrations were estimated from a mathematical model. Poisson regression was used in statistical analyses to estimate the relative risks of exposure to PM2.5 for both sexes and after stratification according to sex. The excess of hospitalizations and consequent excess expenditure for the healthcare system were calculated. RESULTS: There were 1040 admissions, among which 382 had ischemic heart diseases (257 males). Themean PM2.5 concentration was 13.2 µg/m3 (SD = 5.6). Significant effects from exposure were noted 4and 5 days after exposure (lag 4 and lag 5) for both sexes and for male sex; for female sex, the effect was 2 days after exposure (lag 2). There were 59 excess hospitalizations for an increase in PM2.5 concentration of 5 µg/m3 and excess expenditure of US$ 150,000 for the National Health System. CONCLUSIONS: An excess of hospital admissions due to ischemic heart disease, with excess expenditure, was identified consequent to PM2.5 exposure.

Coarse particles and hospital admissions due to respiratory diseases in children. An ecological time series study.

BACKGROUND: Exposure to particulate matter (PM) is associated with hospitalizations due to respiratory diseases among children. DESIGN AND SETTING: An ecological time series study was carried out to identify the role of coarse fractions of particulate matter (PM10-2.5) in hospitalizations among children up to 10 years of age, in Piracicaba (SP) in the year 2015. METHODS: A generalized additive model of Poisson regression was used to estimate the risk of hospitalization due to acute laryngitis and tracheitis, pneumonia, bronchitis, bronchiolitis and asthma. Lags of 0 to 7 days were considered, and the model was adjusted for the temperature and relative humidity of the air and controlled for short and long-term exposure. Proportional attributable ratios, population-attributable fractions and hospital costs were calculated with increasing concentrations of these pollutants. RESULTS: 638 hospitalizations were evaluated during this period, with a mean of 1.75 cases per day (standard deviation, SD = 1.86). The daily averages were 22.45 µg/m3 (SD = 13.25) for the coarse fraction (PM10-2.5) and 13.32 µg/m3 (SD = 6.38) for the fine fraction. Significant risks of PM10-2.5 exposure were only observed at lag 0, with relative risk (RR) = 1.012, and at lag 6, with RR = 1.011. An increase of 5 µg/m3 in the coarse fraction concentration implied an increase in the relative risk of hospitalizations of up to 4.8%, with an excess of 72 hospitalizations and excess expenditure of US$ 17,000 per year. CONCLUSIONS: This study showed the impact of coarse-fraction exposure on hospital admissions among children due to respiratory diseases.

Coarse particles and hospital admissions due to respiratory diseases in children. An ecological time series study

ABSTRACT BACKGROUND: Exposure to particulate matter (PM) is associated with hospitalizations due to respiratory diseases among children. DESIGN AND SETTING: An ecological time series study was carried out to identify the role of coarse fractions of particulate matter (PM10-2.5) in hospitalizations among children up to 10 years of age, in Piracicaba (SP) in the year 2015. METHODS: A generalized additive model of Poisson regression was used to estimate the risk of hospitalization due to acute laryngitis and tracheitis, pneumonia, bronchitis, bronchiolitis and asthma. Lags of 0 to 7 days were considered, and the model was adjusted for the temperature and relative humidity of the air and controlled for short and long-term exposure. Proportional attributable ratios, population-attributable fractions and hospital costs were calculated with increasing concentrations of these pollutants. RESULTS: 638 hospitalizations were evaluated during this period, with a mean of 1.75 cases per day (standard deviation, SD = 1.86). The daily averages were 22.45 µg/m3 (SD = 13.25) for the coarse fraction (PM10-2.5) and 13.32 µg/m3 (SD = 6.38) for the fine fraction. Significant risks of PM10-2.5 exposure were only observed at lag 0, with relative risk (RR) = 1.012, and at lag 6, with RR = 1.011. An increase of 5 µg/m3 in the coarse fraction concentration implied an increase in the relative risk of hospitalizations of up to 4.8%, with an excess of 72 hospitalizations and excess expenditure of US$ 17,000 per year. CONCLUSIONS: This study showed the impact of coarse-fraction exposure on hospital admissions among children due to respiratory diseases.

Fine particulate matter estimated by mathematical model and hospitalizations for pneumonia and asthma in children / Material particulado fino estimado por modelo matemático e internações por pneumonia e asma em crianças

To estimate the association between exposure to fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and hospitalizations for pneumonia and asthma in children. Methods: An ecological study of time series was performed, with daily indicators of hospitalization for pneumonia and asthma in children up to 10 years of age, living in Taubaté (SP) and estimated concentrations of PM2.5, between August 2011 and July 2012. A generalized additive model of Poisson regression was used to estimate the relative risk, with lag zero up to five days after exposure; the single pollutant model was adjusted by the apparent temperature, as defined from the temperature and relative air humidity, seasonality and weekday. Results: The values of the relative risks for hospitalization for pneumonia and asthma were significant for lag 0 (RR=1.051, 95%CI; 1.016 to 1.088); lag 2 (RR=1.066, 95%CI: 1.023 to 1.113); lag 3 (RR=1.053, 95%CI: 1.015 to 1.092); lag 4 (RR=1.043, 95%CI: 1.004 to 1.088) and lag 5 (RR=1.061, 95%CI: 1.018 to 1.106). The increase of 5mcg/m3 in PM2.5 contributes to increase the relative risk for hospitalization from 20.3 to 38.4 percentage points; however, the reduction of 5µg/m3 in PM2.5 concentration results in 38 fewer hospital admissions. Conclusions: Exposure to PM2.5 was associated with hospitalizations for pneumonia and asthma in children younger than 10 years of age, showing the role of fine particulate matter in child health and providing subsidies for the implementation of preventive measures to decrease these outcomes.

Estimar a associação entre exposição ao material particulado fino com diâmetro aerodinâmico inferior a 2,5 micra (PM2.5) e as internações por pneumonia e asma em crianças. Métodos: Estudo ecológico de séries temporais com indicadores diários de internação por pneumonia e asma, em crianças com até 10 anos, residentes em Taubaté (SP), e concentrações estimadas de PM2.5, entre agosto de 2011 e julho de 2012. Modelo aditivo generalizado de regressão de Poisson foi usado para estimar o risco relativo, com defasagem de zero até cinco dias após a exposição; o modelo unipoluente foi ajustado pela temperatura aparente, medida definida a partir da temperatura e umidade relativa do ar, sazonalidade e dia da semana. Resultados: Os valores dos riscos relativos para internações por pneumonia e asma foram significativos para lag 0 (RR=1,051; IC95% 1,016-1,088); lag 2 (RR=1,066; IC95% 1,023-1,113); lag 3 (RR=1,053; IC95% 1,015-1,092); lag 4 (RR=1,043; IC95% 1,004-1,088) e no lag 5 (RR=1,061; IC95% 1,018-1,106). O incremento de 5mcg/m3 de PM2.5 contribui para aumento no risco relativo para internações entre 20,3 a 38,4 pontos percentuais; no entanto, a diminuição de 5µg/m3 na concentração do PM2.5 resulta em menos 38 internações. Conclusões: A exposição ao PM2.5 esteve associada às internações por pneumonia e asma em crianças menores de 10 anos, mostrou o papel do material particulado fino na saúde da criança e forneceu subsídios para implantação de medidas preventivas para diminuírem esses desfechos.

Cytotoxic and genotoxic assessment of surface water from São Paulo State, Brazil, during the rainy and dry seasons.

The aim of this study was to determine if the cytotoxic and genotoxic responses of Allium cepa are effective biomarkers of harmful effects caused by polluted river water and if changes in the responses reflect seasonality in the harmful effects. Samples were collected in the dry season (August 2011 and 2012) and rainy season (February 2012 and 2013) at sampling points on the Jaguari River and the Ribeirão Lavapés, in Brazil. Allium cepa bulbs were exposed to the samples, to positive controls (15 µg/L methyl methanesulfonate), and to negative controls (tap water). Three root tips from each bulb were then stained using the Feulgen reaction, then the micronucleus frequency, the mitotic index, and mitotic anomalies were measured. The total number of anomalies (stickiness, c-mitosis, multipolarity, chromosome bridges, and unidentified anomalies) in the rainy season (8.61 ± 3.65) and dry season (7.07 ± 2.96) were significantly different (U = 11.31, p = 0.04). Toxicity, indicated by the formation of micronuclei and the mitotic index, was higher in the February 2012 samples than in the August 2012 samples. The mean manganese concentration (0.13 mg/L) in the rainy season samples was higher than the maximum concentration permitted by the Brazilian National Environmental Council (<0.1 mg/L) and the manganese concentrations positively correlated with chromosomal aberration induction (p = 0.01, r = 0.69). In conclusion, the rainy season samples were more toxic than the dry season samples. This was probably related to rain water carrying compounds with potentially negative impacts into the rivers. These findings highlight the importance of biomonitoring studies and of treating wastewater in urban areas.

[Fine particulate matter estimated by mathematical model and hospitalizations for pneumonia and asthma in children]. / Material particulado fino estimado por modelo matemático e internações por pneumonia e asma em crianças.

OBJECTIVE: To estimate the association between exposure to fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and hospitalizations for pneumonia and asthma in children. METHODS: An ecological study of time series was performed, with daily indicators of hospitalization for pneumonia and asthma in children up to 10 years of age, living in Taubaté (SP) and estimated concentrations of PM2.5, between August 2011 and July 2012. A generalized additive model of Poisson regression was used to estimate the relative risk, with lag zero up to five days after exposure; the single pollutant model was adjusted by the apparent temperature, as defined from the temperature and relative air humidity, seasonality and weekday. RESULTS: The values of the relative risks for hospitalization for pneumonia and asthma were significant for lag 0 (RR=1.051, 95%CI; 1.016 to 1.088); lag 2 (RR=1.066, 95%CI: 1.023 to 1.113); lag 3 (RR=1.053, 95%CI: 1.015 to 1.092); lag 4 (RR=1.043, 95%CI: 1.004 to 1.088) and lag 5 (RR=1.061, 95%CI: 1.018 to 1.106). The increase of 5mcg/m(3) in PM2.5 contributes to increase the relative risk for hospitalization from 20.3 to 38.4 percentage points; however, the reduction of 5µg/m(3) in PM2.5 concentration results in 38 fewer hospital admissions. CONCLUSIONS: Exposure to PM2.5 was associated with hospitalizations for pneumonia and asthma in children younger than 10 years of age, showing the role of fine particulate matter in child health and providing subsidies for the implementation of preventive measures to decrease these outcomes.

[Association between exposure to particulate matter and hospital admissions for respiratory disease in children]. / Associação entre exposição ao material particulado e internações por doenças respiratórias em crianças.

The aim of this study was to estimate the association between exposure to particulate matter less than 2.5 microns in diameter and hospitalization for respiratory disease. It was an ecological time series study with daily indicators of hospitalization for respiratory diseases in children up to 10 years old, living in Piracicaba, SP, Southeastern Brazil, between August 1, 2011 and July 31, 2012. A generalized additive Poisson regression model was used. The relative risks were RR = 1.008; 95%CI 1.001;1.016 for lag 1 and RR = 1.009; 95%CI 1.001;1.017 for lag 3. The increment of 10 µg/m3 in particulate matter less than 2.5 microns in diameter implies increase in relative risk of between 7.9 and 8.6 percentage points. In conclusion, exposure to particulate matter less than 2.5 microns in diameter was associated with hospitalization for respiratory disease in children.

Associação entre características pessoais, organização do trabalho e presença de dor em funcionários de uma indústria moveleira / Association between personal traits, labour organization and occurrence of pain in employees at a furniture manufacturer

Os distúrbios osteomusculares relacionados ao trabalho são afecções que atingem os tecidos moles. Têm um nexo causal com fatores de risco ergonômicos e um caráter insidioso e multifatorial, apresentando como sintoma comum dores musculoesqueléticas. O objetivo deste estudo foi investigar possível associação entre características pessoais, organização do trabalho e presença de dor em funcionários de uma indústria moveleira no município de Araçatuba, SP. Foi aplicado um questionário a uma amostra de 158 funcionários de diversos setores da empresa, com questões de caráter sociodemográfico (sexo, idade), trabalhista (setor, tempo de serviço, função desempenhada e jornada de trabalho semanal), bem como sobre sintomas dolorosos musculoesqueléticos. Dor foi relatada por 58,9% dos funcionários e relacionada de maneira significativa com o sexo (p=0,0001), setor de trabalho (p=0,0021), função desempenhada (p=0,0135) e jornada de trabalho semanal (p=0,0123). A dor predominou em mulheres, dependendo do setor, da função desempenhada e da jornada de trabalho semanal. Para tentar saná-la, a maioria dos trabalhadores usa medicamentos ou adota a atitude de ignorá-la. Os resultados sugerem a necessidade de intervenção fisioterapêutica preventiva...

Work-related musculoskeletal disorders are diseases that affect the soft tissues. Of an insidious and multifactor nature, they often result from ergonomic risks, and show pains as a common symptom. This study searched for possible associations between personal features, labour organization and pain incidence among employees at a furniture manufacturer in the city of Araçatuba, SP. A questionnaire was administered to a sample of 158 employees from the company’s different sectors in 2007, with questions addressing age and sex, labour issues(sector, seniority, position, and weekly working hours), as well as musculoskeletal pain symptoms. P in was reported by 58.9% of the employees and significantly related to gender (p=0.0001), sector (p=0.0021), position (p=0.0135), and weekly working hours (p=0.0123). Pain was predominant in women, depending on sector, position, and weekly working hours. In order to relieve pain, most workers took medicine or simply ignored it. Results point to the need to physical therapy treatment and preventive action...

Comparison of histological and molecular diagnosis of Helicobacter pylori in benign lesions and gastric adenocarcinoma

A colonização do Helicobacter pylori está associada com gastrite crônica, úlcera péptica, metaplasia intestinal, adenocarcinoma e linfoma gástrico. O objetivo desse estudo foi comparar os resultados do diagnóstico histológico usado de rotina na detecção do H. pylori com o diagnóstico molecular. Foram utilizadas amostras de 80 lesões gástricas (gastrite crônica, gastrite atrófica, úlcera gástrica e metaplasia intestinal), 18 amostras de adenocarcinoma gástrico e 10 amostras de mucosa gástrica normal H. pylori negativas (controle). Todas as amostras foram avaliadas histologicamente (coloração com hematoxilina-eosina e Giemsa) e pela PCR com a amplificação dos genes antígeno espécie-específico (H3H4) e urease A (H5H6) do H. pylori e pelo gene humano CYP1A1, como controle da qualidade do DNA. Nas amostras de lesão benigna e adenocarcinoma gástrico, a infecção foi detectada em 43 per center (42/98) e 71 pe center (70/98), respectivamente, para os diagnósticos histológico e molecular (p = 0,0001). O teste de PCR detectou o H. pylori em 27,5 per center (22/80) das lesões gástricas benignas e em 50 per center (9/18) dos adenocarcinomas gástricos, com diagnóstico histológico negativo para essa bactéria. Cerca de 2,5 per center das amostras, exclusivamente de lesões benignas, com diagnóstico histológico positivo apresentaram resultado molecular negativo, para ambos os primers. Diferenças estatisticamente significantes foram encontradas entre os métodos histológico e molecular, em metaplasia intestinal (p = 0,0461) e adenocarcinoma gástrico (p = 0,0011), devido à subdetecção do H. pylori pelo método histológico, e provavelmente pela baixa densidade da bactéria conseqüente à atrofia severa da mucosa gástrica, nesses dois tipos de lesões. Nossos achados demonstram que o método de PCR é mais eficaz para diagnosticar a infecção por H. pylori, principalmente, em metaplasia intestinal e adenocarcinoma gástrico.

Aneuploidies, deletion, and overexpression of TP53 gene in intestinal metaplasia of patients without gastric cancer.

Gastric carcinogenesis is attributable to interacting environmental and genetic factors, through a sequence of events including intestinal metaplasia. Using a fluorescence in situ hybridization technique, we investigated the occurrence of aneuploidies of chromosomes 3, 7, 8, 9, and 17, TP53 gene deletion, and expression of p53 in 21 intestinal metaplasia (IM) samples from cancer-free patients and in 20 gastric adenocarcinoma samples. Aneuploidies were found in 71% (15/21) of the IM samples. Trisomy of chromosomes 7 and 9 occurred mainly in complete-type IM; in the incomplete type, trisomy of chromosomes 7 and 8 were more commonly found. The TP53 gene deletion was observed in 60% (3/5) of the IM cases, and immunohistochemistry revealed p53 overexpression in 12% (2/17) of the analyzed IM cases. All gastric adenocarcinoma cases presented higher frequencies of trisomy or tetrasomy of chromosomes 3, 7, 8, 9, and 17. The TP53 deletion was found in all three of the gastric adenocarcinoma analyzed for it, and immunohistochemistry detected overexpression of protein p53 in 80% (12/15) of the analyzed cases. Our study revealed for the first time the presence of aneuploidies of chromosomes 7, 8, 9, and 17 and of TP53 gene deletion and overexpression in IM samples from cancer-free patients. These results suggest that IM and gastric adenocarcinoma may share the same genetic alterations.

Fatores genéticos e ambientais envolvidos na carciogênese gástrica / Genetics and environmental factors in gastric carcinogenesis

RACIONAL: O câncer de estômago é o segundo tipo mais comum de neoplasia no mundo. A carcinogênese de estômago é processo de múltiplos passos, podendo manifestar-se em várias etapas como gastrite superficial, gastrite atrófica crônica, metaplasia intestinal, displasia e, finalmente, como um carcinoma. Essas condiçöes costumam ser seqüenciais e ocorrer num período de muitos anos como resultado da exposiçäo a uma variedade de fatores endógenos e exógenos, que causam alteraçöes genéticas. Os recentes avanços da genética molecular têm mostrado que o acúmulo dessas várias anormalidades, incluindo a ativaçäo de oncogenes e a inativaçäo de genes supressores de tumores, resultam no desenvolvimento do câncer. Alteraçöes genéticas descritas em carcinomas gástricos incluem amplificaçöes e mutaçöes dos genes c-ERBB2, K-RAS, c-MET e TP53. O ganho de cromossomos também foi encontrado em várias combinaçöes com perda de outros cromossomos e pode estar associado com a expressäo elevada de oncogenes, que contribuem com a progressäo tumoral. CONCLUSÄO: Essas mudanças genéticas em carcinomas evidenciam o processo de múltiplas etapas da carcinogênese gástrica, por meio do acúmulo de uma série de alteraçöes

[Genetics and environmental factors in gastric carcinogenesis]. / Fatores genéticos e ambientais envolvidos na carciogônese gástrica.

BACKGROUND: Gastric cancer is considered to be the second most common cancer worldwide. Carcinogenesis of the stomach is a multi-stage process. The progression from normal epithelial to tumor cells may involve at least five stages: superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and carcinoma. These sequential changes in the gastric mucosa may occur over a period of many years as a result of exposure to a variety of exogenous and/or endogenous factors which cause genetic alterations. Recent developments in molecular genetics have shown that the accumulation of these multiple genetic alterations, including activation of oncogenes and inactivation of tumor-suppressor genes, results in cancer development. Genetic alterations previously reported in gastric carcinomas include amplifications or mutations of the c-ERBB2, K-RAS, c-MET and TP53. Chromosomal gains were also found in various combinations with chromosomal losses and may be associated with the overexpression of dominant oncogenes contributing to tumor progression. CONCLUSIONS: These accumulated genetic changes in carcinomas provide evidences for the stepwise mode of gastric carcinogenesis through the accumulation of a series of genetic alterations.