RESUMO
Colombia, South America has one of the world's highest burdens of Helicobacter pylori infection and gastric cancer. While multidrug antibiotic regimens can effectively eradicate H. pylori, treatment efficacy is being jeopardized by the emergence of antibiotic-resistant H. pylori strains. Moreover, the spectrum of and genetic mechanisms for antibiotic resistance in Colombia is underreported. In this study, 28 H. pylori strains isolated from gastric biopsy specimens from a high-gastric-cancer-risk (HGCR) population living in the Andes Mountains in Túquerres, Colombia and 31 strains from a low-gastric-cancer-risk (LGCR) population residing on the Pacific coast in Tumaco, Colombia were subjected to antibiotic susceptibility testing for amoxicillin, clarithromycin, levofloxacin, metronidazole, rifampin, and tetracycline. Resistance-associated genes were amplified by PCR for all isolates, and 29 isolates were whole-genome sequenced (WGS). No strains were resistant to amoxicillin, clarithromycin, or rifampin. One strain was resistant to tetracycline and had an A926G mutation in its 16S rRNA gene. Levofloxacin resistance was observed in 12/59 isolates and was significantly associated with N87I/K and/or D91G/Y mutations in gyrA Most isolates were resistant to metronidazole; this resistance was significantly higher in the LGCR (31/31) group compared to the HGCR (24/28) group. Truncations in rdxA and frxA were present in nearly all metronidazole-resistant strains. There was no association between phylogenetic relationship and resistance profiles based on WGS analysis. Our results indicate H. pylori isolates from Colombians exhibit multidrug antibiotic resistance. Continued surveillance of H. pylori antibiotic resistance in Colombia is warranted in order to establish appropriate eradication treatment regimens for this population.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Colômbia/epidemiologia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/genética , Humanos , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Filogenia , RNA Ribossômico 16S/genética , RNA Ribossômico 23S , América do Sul , Neoplasias Gástricas/tratamento farmacológicoRESUMO
BACKGROUND & AIMS: Helicobacter pylori eradication and endoscopic surveillance of gastric precancerous lesions are strategies to reduce gastric cancer (GC) risk. To our knowledge, this study is the longest prospective cohort of an H pylori eradication trial in a Hispanic population. METHODS: A total of 800 adults with precancerous lesions were randomized to anti-H pylori treatment or placebo. Gastric biopsy samples taken at baseline and 3, 6, 12, 16, and 20 years were assessed by our Correa histopathology score. A generalized linear mixed model with a participant-level random intercept was used to estimate the effect of H pylori status on the score over time. Logistic regression models were used to estimate progression by baseline diagnosis and to estimate GC risk by intestinal metaplasia (IM) subtype and anatomic location. RESULTS: Overall, 356 individuals completed 20 years of follow-up. Anti-H pylori therapy (intention-to-treat) reduced progression of the Correa score (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.38-0.93). H pylori-negative status had a beneficial effect on the score over time (P = .036). Among individuals with IM (including indefinite for dysplasia) at baseline, incidence rates per 100 person-years were 1.09 (95% CI, 0.85-1.33) for low-grade/high-grade dysplasia and 0.14 (95% CI, 0.06-0.22) for GC. Incomplete-type (vs complete-type) IM at baseline presented higher GC risk (OR, 13.4; 95% CI, 1.8-103.8). Individuals with corpus (vs antrum-restricted) IM showed an OR of 2.1 (95% CI, 0.7-6.6) for GC. CONCLUSIONS: In a high-GC-risk Hispanic population, anti-H pylori therapy had a long-term beneficial effect against histologic progression. Incomplete IM is a strong predictor of GC risk.
Assuntos
Antibacterianos/uso terapêutico , Mucosa Gástrica/patologia , Infecções por Helicobacter/tratamento farmacológico , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Adulto , Idoso , Biópsia , Colômbia/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/microbiologia , Gastroscopia/estatística & dados numéricos , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Masculino , Metaplasia/diagnóstico , Metaplasia/epidemiologia , Metaplasia/microbiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Colombians in coastal Tumaco have a lower incidence of Helicobacter pylori-associated gastric cancer compared to individuals from Tuquerres in the high Andes. This is despite nearly universal prevalence of H. pylori infection and chronic gastritis. METHODS: H. pylori infection was confirmed by Steiner stain and serology using African and European-origin strains. Gastric histology and serum inflammatory biomarkers in dyspeptic Tumaco or Tuquerres patients were evaluated to predict progression of gastric lesions. RESULTS: H. pylori infection was nearly universal by Steiner stain and serology. IgG response to European-origin H. pylori strains were greater than African-origin. High gastric cancer-risk Tuquerres patients, compared to low-risk Tumaco, had significant odds ratios for lesion progression associated with serum IL-5, trefoil factor 3 (TFF3), and low pepsinogen I/II ratio. Sensitivity and specificity for these parameters was 63.8% and 67.9%, respectively, with correctly classifying patients at 66.7%. Most odds ratios for 26 other biomarkers were significant for the town of residency, indicating an environmental impact on Tumaco patients associated with decreased lesion progression. CONCLUSION: An IL-5 association with progression of gastric lesions is novel and could be evaluated in addition to TFF3 and pepsinogen I/II ratio as a non-invasive prognostic screen. Results suggest Tumaco patients were exposed to infectious diseases beyond H. pylori such as the documented high incidence of helminthiasis and toxoplasmosis. IMPACT: Results support a prior recommendation to evaluate TFF3 and pepsinogen I/II together to predict aggressive gastric histology. Our data indicate IL-5 should be further evaluated as prognostic parameter.
Assuntos
Biomarcadores/sangue , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Interleucina-5/sangue , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/epidemiologia , Fator Trefoil-3/sangue , Adulto , Estudos de Casos e Controles , Colômbia/epidemiologia , Feminino , Infecções por Helicobacter/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologiaRESUMO
We present here the draft genomes of 13 Helicobacter pylori strains isolated from Colombian residents on the Pacific coast (n = 6) and in the Andes mountains (n = 7), locations that differ in gastric cancer risk. These 13 strains were obtained from individuals with diagnosed gastric lesions.
RESUMO
Inhabitants of Túquerres in the Colombian Andes have a 25-fold higher risk of gastric cancer than inhabitants of the coastal town Tumaco, despite similar H. pylori prevalences. The gastric microbiota was recently shown in animal models to accelerate the development of H. pylori-induced precancerous lesions. 20 individuals from each town, matched for age and sex, were selected, and gastric microbiota analyses were performed by deep sequencing of amplified 16S rDNA. In parallel, analyses of H. pylori status, carriage of the cag pathogenicity island and assignment of H. pylori to phylogeographic groups were performed to test for correlations between H. pylori strain properties and microbiota composition. The gastric microbiota composition was highly variable between individuals, but showed a significant correlation with the town of origin. Multiple OTUs were detected exclusively in either Tumaco or Túquerres. Two operational taxonomic units (OTUs), Leptotrichia wadei and a Veillonella sp., were significantly more abundant in Túquerres, and 16 OTUs, including a Staphylococcus sp. were significantly more abundant in Tumaco. There was no significant correlation of H. pylori phylogeographic population or carriage of the cagPAI with microbiota composition. From these data, testable hypotheses can be generated and examined in suitable animal models and prospective clinical trials.
Assuntos
Microbiota , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Estômago/microbiologia , Adulto , Colômbia/epidemiologia , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Masculino , Metagenoma , Metagenômica , Pessoa de Meia-Idade , Risco , Neoplasias Gástricas/diagnósticoAssuntos
Animais , Humanos , Masculino , Camundongos , Ratos , Butadienos/farmacocinética , Carcinógenos/farmacocinética , Compostos de Epóxi/farmacocinética , Butadienos/toxicidade , Compostos de Epóxi/toxicidade , Glutationa/metabolismo , Modelos Biológicos , Ratos Sprague-Dawley , Especificidade da EspécieRESUMO
BACKGROUND: The role of processed meat in the aetiology of squamous cell oesophageal cancer has been explored in detail. METHODS: In the time period 1990-2005, a case-control study was conducted in Montevideo, Uruguay including 2,368 participants (876 cases of oesophageal cancer and 1,492 controls). Relative risks, approximated by the odds ratios, were estimated by multiple unconditional logistic regression. RESULTS: Processed meat was positively associated with oesophageal cancer (upper quartile vs lower quartile OR 2.30, 95%CI 1.72-3.07), whereas salted meat intake was positively associated with squamous cell oesophageal cancer (OR 3.82, 95%CI 2.74-5.33). Finally other cured meats were positively associated with oesophageal cancer (OR 1.65, 95%CI 1.22- 2.22). CONCLUSIONS: It could be concluded that processed meat consumption could be an important risk factor for the aetiology of squamous cell oesophageal cancer in Uruguay.
Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Comportamento Alimentar , Produtos da Carne/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Carcinoma de Células Escamosas do Esôfago , Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fumar/epidemiologia , Cloreto de Sódio , Uruguai/epidemiologiaRESUMO
BACKGROUND: Oesophageal cancer presents high incidence rates in the so-called Brazilian-Uruguayan belt. MATERIALS AND METHODS: The present study included 1,170 participants (234 cases and 936 controls) which were analyzed by unconditional multiple logistic regression in order to examine risk of oesophageal squamous cell carcinoma (OESCC) associated with several food groups. RESULTS: Boiled red meat (OR 2.59, 95%CI 1.69-3.97), lamb meat (OR 1.64, 95%CI 1.07-2.51), processed meat (OR 1.49, 95%CI 1.01-2.21), whole milk (OR 1.78, 1.19-1.68), fresh vegetables and fruits (OR 0.42, 95%CI 0.27-0.63), mate consumption (OR 2.04, 95%CI 1.32- 3.16), and black tea (OR 0.10, 95%CI 0.04-0.28) were significantly associated with risk of OESCC. CONCLUSIONS: Hot beverages (mate) and hot foods (boiled meat) appear to be important determinants in the risk of OESCC, allowing the penetration of carcinogens in tobacco and alcohol into the oesophageal mucosa.
Assuntos
Carcinoma de Células Escamosas/etiologia , Dieta/efeitos adversos , Neoplasias Esofágicas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Neoplasias Esofágicas/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Uruguai/epidemiologiaRESUMO
BACKGROUND & AIMS: The gastric cancer-causing pathogen Helicobacter pylori up-regulates spermine oxidase (SMOX) in gastric epithelial cells, causing oxidative stress-induced apoptosis and DNA damage. A subpopulation of SMOX(high) cells are resistant to apoptosis, despite their high levels of DNA damage. Because epidermal growth factor receptor (EGFR) activation can regulate apoptosis, we determined its role in SMOX-mediated effects. METHODS: SMOX, apoptosis, and DNA damage were measured in gastric epithelial cells from H. pylori-infected Egfr(wa5) mice (which have attenuated EGFR activity), Egfr wild-type mice, or in infected cells incubated with EGFR inhibitors or deficient in EGFR. A phosphoproteomic analysis was performed. Two independent tissue microarrays containing each stage of disease, from gastritis to carcinoma, and gastric biopsy specimens from Colombian and Honduran cohorts were analyzed by immunohistochemistry. RESULTS: SMOX expression and DNA damage were decreased, and apoptosis increased in H. pylori-infected Egfr(wa5) mice. H. pylori-infected cells with deletion or inhibition of EGFR had reduced levels of SMOX, DNA damage, and DNA damage(high) apoptosis(low) cells. Phosphoproteomic analysis showed increased EGFR and erythroblastic leukemia-associated viral oncogene B (ERBB)2 signaling. Immunoblot analysis showed the presence of a phosphorylated (p)EGFR-ERBB2 heterodimer and pERBB2; knockdown of ErbB2 facilitated apoptosis of DNA damage(high) apoptosis(low) cells. SMOX was increased in all stages of gastric disease, peaking in tissues with intestinal metaplasia, whereas pEGFR, pEGFR-ERBB2, and pERBB2 were increased predominantly in tissues showing gastritis or atrophic gastritis. Principal component analysis separated gastritis tissues from patients with cancer vs those without cancer. pEGFR, pEGFR-ERBB2, pERBB2, and SMOX were increased in gastric samples from patients whose disease progressed to intestinal metaplasia or dysplasia, compared with patients whose disease did not progress. CONCLUSIONS: In an analysis of gastric tissues from mice and patients, we identified a molecular signature (based on levels of pEGFR, pERBB2, and SMOX) for the initiation of gastric carcinogenesis.
Assuntos
Dano ao DNA , Células Epiteliais/enzimologia , Receptores ErbB/metabolismo , Mucosa Gástrica/enzimologia , Infecções por Helicobacter/enzimologia , Helicobacter pylori/metabolismo , Receptor ErbB-2/metabolismo , Animais , Apoptose , Linhagem Celular , Sobrevivência Celular , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Técnicas de Cocultura , Colômbia , Progressão da Doença , Ativação Enzimática , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Receptores ErbB/deficiência , Receptores ErbB/genética , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/enzimologia , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Honduras , Humanos , Metaplasia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Fosforilação , Lesões Pré-Cancerosas/enzimologia , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Análise de Componente Principal , Multimerização Proteica , Receptor ErbB-2/genética , Transdução de Sinais , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Tennessee , Poliamina OxidaseRESUMO
BACKGROUND: In developing countries, more than 50% of children have serological evidence of Helicobacter pylori infection. However, serological tests for H. pylori did not differentiate between active and past infection. The objectives of this study were to estimate the frequency of active and past H. pylori infection utilizing functional urea breath test (UBT) and serological tests and evaluate factors associated with the infection. METHODS: A total of 675 school children, 6-13 years of age, participated. UBT was performed to detect active H. pylori infection. Blood samples were obtained to determine iron status and Immunoglobulin G (IgG) responses to the H. pylori whole-cell and to Cag A antigens by antigen-specific enzyme-linked immunosorbent assays. Weight, height, and sociodemographic characteristics were recorded. RESULTS: A total of 37.9% (95% Confidence Intervals (CI): 34.2-41.6) of school children had active or past H. pylori infection; of them, 73.8% (CI95% 68.4-79.2) were carrying CagA-positive strain, 26.5% (CI95% 23.2-29.8) had active infection, and 11.4% (95%CI: 9.0-13.8) had evidence of past H. pylori infection. School children with iron deficiency and low height for age had higher risk of H. pylori infection: [OR to active or past infection was 2.30 (CI 95% 1.01-5.23) and to active infection it was 2.64 (CI 95% 1.09-6.44)] compared to school children with normal iron status and height for age or with normal iron status but low height for age or with iron deficiency and normal height for age. CONCLUSIONS: The estimated prevalence of infection depends of the test utilized. Frequency of H. pylori infection and carrying CagA-positive strains was high in this population. Malnutrition was associated with active H. pylori infection.