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1.
J Clin Oncol ; : JCO2400948, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935899
2.
Clin Transl Gastroenterol ; 15(6): e1, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38742743

RESUMO

INTRODUCTION: We designed a race-conscious study to assess the presence of Helicobacter pylori v irulence factor cagA in a retrospective cohort of patients with active H. pylori infection. METHODS: We compared cagA status by race in gastric tissue samples from 473 patients diagnosed with active H. pylori infection from 2015 to 2019. RESULTS: H. pylori + Black patients were 2 times more likely to be cagA + than H. pylori + White patients (82% vs 36%, P < .0001). DISCUSSION: Presence of cagA is common among endoscopy patients with active H. pylori infection; appropriate testing and treatment of H. pylori can both reduce gastric cancer risk and address health disparities.


Assuntos
Antígenos de Bactérias , Proteínas de Bactérias , Infecções por Helicobacter , Helicobacter pylori , Fatores de Virulência , Humanos , Helicobacter pylori/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Antígenos de Bactérias/análise , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prevalência , Fatores de Virulência/análise , Adulto , Idoso , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/epidemiologia , População Branca/estatística & dados numéricos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Negro ou Afro-Americano/estatística & dados numéricos
3.
South Med J ; 117(4): 199-205, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38569609

RESUMO

OBJECTIVES: Eradication of Helicobacter pylori reduces the risk of gastric cancer (GC). Individuals with type 2 diabetes mellitus (T2DM) are known to be at increased risk for GC. In a cohort of H. pylori-positive individuals, we assessed whether those with T2DM were at risk of persistent infection following H. pylori treatment compared with individuals without T2DM. METHODS: A random subset of all individuals diagnosed as having H. pylori without intestinal metaplasia at endoscopy from 2015 to 2019 were stratified evenly by race (Black and White). After excluding those with T1DM and those without eradication testing after H. pylori treatment, logistic regression analysis was used to determine the association of T2DM with the risk of persistent H. pylori infection following treatment. RESULTS: In 138 patients, H. pylori eradication rates did not differ between the 27% of individuals with T2DM compared to those without (81.1% vs 81.2%). After adjusting for age, race, and insurance status, we found no significant increased risk of persistent H. pylori infection for individuals with T2DM (odds ratio 1.40; 95% confidence interval 0.49-3.99). CONCLUSIONS: H. pylori eradication rates do not differ by T2DM status, providing support for clinical trials of H. pylori eradication to reduce GC incidence among high-risk populations in the United States, such as individuals with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Antibacterianos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Neoplasias Gástricas/diagnóstico , População Negra , População Branca
5.
Gastric Cancer ; 27(1): 28-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37985571

RESUMO

BACKGROUND: Gastric cancer (GC) accounts for the greatest disparity in cancer mortality between Black and White Americans. Although clinical trials have shown that Helicobacter pylori (Hp) treatment reduces risk of GC, Hp testing and treatment is not consistently performed in the US, and may offer an opportunity to improve survival. METHODS: In a diverse retrospective cohort of 99 GC cases diagnosed at Duke University from 2002-2020 (57% Black; 43% white), we examined the association of Hp testing and treatment prior to or at cancer diagnosis with overall survival using Cox regression analyses to calculate adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Overall, 62% of patients were tested for Hp prior to or at GC diagnosis. Of those, 25% tested positive and were treated < 1 year prior to or at diagnosis, 15% tested positive and were treated ≥ 1 year prior to diagnosis, 6% tested positive without evidence of treatment, and 54% tested negative. Compared to never tested, Hp testing and treatment < 1 year prior to or at diagnosis was associated with a significantly reduced likelihood of death (HR 0.21, 95% CI 0.08-0.58). The benefit of any Hp test and treat prior to or at GC diagnosis was significant even among stage IV patients only (HR, 0.22; 95% CI 0.05-0.96). CONCLUSIONS: These findings support Hp testing and treatment for patients at risk of or diagnosed with GC, and suggest Hp treatment may provide an opportunity to reduce GC mortality disparities in the US.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/epidemiologia , Estudos Retrospectivos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/complicações , Modelos de Riscos Proporcionais
7.
Cancer Causes Control ; 34(10): 897-907, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37310566

RESUMO

PURPOSE: Gastric cancer remains a racial health disparity in the US, but few studies have examined supplements as a potential protective factor. We examined associations between regular supplement use and gastric cancer risk among the predominantly Black participants in the Southern Community Cohort Study (SCCS). METHODS: Of the 84,508 individuals recruited in the SCCS from 2002 to 2009, 81,884 responded to the baseline question: any vitamin or supplement taken at least once per month in the past year. Secondary analyses assessed specific supplement use. Associations with incident gastric cancer were examined using adjusted Cox proportional hazards models, stratified by histologic subtype and secondarily by healthy eating index (HEI). RESULTS: Approximately half of the participants (47%, n = 38,318) reported any regular supplement use. Among the 203 incident gastric cancers over the follow-up period (median, 7 years), 142 were non-cardia (NCGC), 31 cardia (CGC), and 30 unknown. Regular supplement use was associated with a 30% decreased risk of NCGC (hazards ratio (HR) 0.70; 95% confidence interval (CI) 0.49-0.99). Among participants below the HEI median, any regular supplement and multivitamin use were associated with a 52% and 70% decrease in risk of NCGC (HR 0.48; 95%CI 0.25-0.92 and HR 0.30; 95%CI 0.13-0.71), respectively. No associations were found for CGC. CONCLUSION: Regular supplement use, including multivitamins, was associated with a decreased risk of NCGC in the SCCS, particularly among participants with a lower quality diet. Inverse associations of supplement use and NCGC incidence provide support for clinical trials among high-risk populations in the US.


Assuntos
Neoplasias Gástricas , Humanos , Estudos de Coortes , Neoplasias Gástricas/epidemiologia , Suplementos Nutricionais , Fatores de Risco , Vitaminas
8.
Cancer Epidemiol Biomarkers Prev ; 32(4): 473-486, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37009691

RESUMO

Gastric cancer, the fifth leading cause of cancer worldwide, is estimated to be responsible for approximately 1.4% of all new cancers and 1.8% of all cancer-related deaths in the United States. Despite declining incidence rates and improved survival rates, however, gastric cancer continues to disproportionately affect racial and ethnic minorities and individuals of lower socioeconomic status at higher rates than the general population. To improve outcomes globally and address disparities within the United States, continued improvements are needed in risk factor modification and biomarker development and to improve access to existing preventative measures such as genetic testing and H. pylori eradication testing, in addition to expanding upon current clinical guidelines for premalignant disease to address gaps in endoscopic surveillance and early detection.


Assuntos
Infecções por Helicobacter , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Estados Unidos/epidemiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Neoplasias Gástricas/diagnóstico , Fatores de Risco , Grupos Raciais , Lesões Pré-Cancerosas/epidemiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/diagnóstico , Incidência
10.
Asian Pac J Cancer Prev ; 24(3): 935-943, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36974548

RESUMO

BACKGROUND: Seropositivity to certain Helicobacter pylori proteins may affect development of gastric lesions that could become cancerous. Previously, we developed a model of gastric cancer risk including gender, age, HP0305 sero-positivity, HP1564 sero-positivity, UreA antibody titer and serologically defined chronic atrophic gastritis (termed: "Lasso model"). METHODS: We evaluated the Lasso model's ability to discriminate individuals with precancerous gastric lesions (n=320) from individuals with superficial or mild atrophic gastritis (n=226) in Linqu County, China, a population at high risk for gastric cancer. We also compared its performance to the ABC Method, a gastric cancer risk stratification tool currently used in East Asia. RESULTS: For distinguishing precancerous lesions from those with gastritis, the receiver operating characteristic curve had an area under the curve (AUC) of 73.41% (95% CI: 69.10%, 77.71%) and, at Youden's Index, a sensitivity of 78.44% (59.38%, 82.50%) and specificity of 64.72% (95% CI: 58.85%, 81.42%). Positive predictive value (PPV) was 75.38% (72.78%, 82.51%). Specificity, AUC and PPV were significantly greater (p < 0.05) than those of the ABC Method. When specificity was held constant, the Lasso model had greater sensitivity, PPV and negative predictive value (NPV) than the ABC Method. However, adjusting the ABC Method for age and gender negated the Lasso model's significant improvement in AUC. CONCLUSIONS: The Lasso model for gastric cancer risk prediction can classify precancerous lesions with significantly greater AUC than the ABC Method and, at constant specificity, with greater sensitivity, PPV and NPV. However, adding age and gender to the ABC Method, as included in the Lasso model, substantially improved its performance and negated the Lasso model's advantage.


Assuntos
Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Gastrite Atrófica/diagnóstico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/patologia , Gastrite/diagnóstico , Gastrite/patologia , Lesões Pré-Cancerosas/patologia , Medição de Risco
11.
Gastroenterology ; 164(5): 736-751, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36706842

RESUMO

Gastric cancer (GC) is a leading cause of global mortality but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology, critically appraise strategies of prevention and disease attenuation, and assess how these strategies could be applied to improve outcomes from GC in a world of variable risk and disease burden. Strategies of primary prevention focus on improving the detection and eradication of the main environmental risk factor, Helicobacter pylori. In certain countries of high incidence, endoscopic or radiographic screening of the asymptomatic general population has been adopted as a means of secondary prevention. By contrast, identification and targeted surveillance of individuals with precancerous lesions (such as intestinal metaplasia) is being increasingly embraced in nations of low incidence. This review also highlights existing knowledge gaps in GC prevention as well as the role of emerging technologies for early detection and risk stratification.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/patologia , Endoscopia/efeitos adversos , Incidência , Metaplasia/patologia , Mucosa Gástrica/patologia , Fatores de Risco
12.
Gastro Hep Adv ; 1(5): 857-868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36381169

RESUMO

BACKGROUND AND AIMS: Helicobacter pylori remains an important risk factor for noncardia gastric cancer and a spectrum of disease from H. pylori infection to gastric cancer. As a step toward improved clinical strategies for gastric cancer prevention, we assessed racial differences in prevalence of H. pylori from studies across the United States. This systematic review provides a comprehensive evaluation of the literature regarding racial differences in H. pylori in the United States. METHODS: MEDLINE, Embase, and Web of Science database searches were performed through May 26, 2021. Ultimately, 25 studies that reported H. pylori infection prevalence by race were included. RESULTS: All studies included in the review documented higher H. pylori prevalence in Blacks and Hispanics than in whites. The ratio of H. pylori prevalence for Blacks compared to non-Hispanic whites ranged from 1.3 to 5.4, and the ratio for Hispanics compared to non-Hispanic whites ranged from 1.8 to 4.4. Of the 5 studies that examined H. pylori CagA prevalence by race, 4 found higher prevalence among Blacks and Hispanics compared to whites, with CagA prevalence ranging from 19% to 77% in whites, 62% to 90% in Blacks, and 64% to 74% in Hispanics. CONCLUSION: In this review, across 25 studies, varying in underlying population, time period, and geographic location, Blacks and Hispanics appeared to have a higher prevalence of H. pylori infection than whites. This increased prevalence of H. pylori among populations also at a higher risk of gastric cancer is relevant in the clinical setting for decision-making related to H. pylori testing and gastric cancer prevention.

13.
Cancer Epidemiol Biomarkers Prev ; 31(7): 1426-1432, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35534235

RESUMO

BACKGROUND: Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric cancer precursor, and may be useful to detect persons at increased risk of gastric cancer. METHODS: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the United States between 1993 and 2001. ELISA-based pepsinogen tests were conducted on prediagnostic serum samples of 105 PLCO participants who developed gastric cancer and 209 age, sex, and race-matched controls. Pepsinogen positive (PG+) was defined as pepsinogen I ≤ 70 µg/L and pepsinogen I/II ratio ≤3.0. Results of conditional logistic regression models, and sensitivity and specificity, of PG+ for gastric cancer are reported. RESULTS: Gastric cancer cases were more likely to be PG+ (31.4% vs. 5.5%, P < 0.001) at baseline than controls. Compared to PG-, PG+ was associated with an 8.5-fold increased risk for gastric cancer [95% confidence interval (CI) = 3.8-19.4]. This risk remained significant after adjusting for Helicobacter pylori, family history of gastric cancer, education, smoking, and BMI (aOR, 10.6; 95% CI, 4.3-26.2). In subgroup analysis, PG+ individuals were 11-fold more like to develop non-cardia gastric cancer (OR, 11.1; 95% CI, 4.3-28.8); conversely, they were not significantly more likely to develop cardia gastric cancer (OR, 2.0; 95% CI = 0.3-14.2). PG+ status yielded low sensitivity but high specificity for both noncardia (44.3%; 93.6%) and cardia gastric cancer (5.7%; 97.2%). CONCLUSIONS: Prediagnostic serum pepsinogen levels from a large, prospective cohort study were associated with risk of gastric cancer, particularly noncardia gastric cancer. IMPACT: PG status may identify individuals at higher risk of noncardia gastric cancer for targeted screening or interventions. See related commentary by Zhou and Huang, p. 1257.


Assuntos
Pepsinogênio A , Pepsinogênio C , Neoplasias Gástricas , Biomarcadores , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Detecção Precoce de Câncer , Gastrite Atrófica , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Masculino , Estudos Prospectivos , Próstata , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Estados Unidos/epidemiologia
15.
Cancer Epidemiol Biomarkers Prev ; 31(4): 811-820, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35131882

RESUMO

BACKGROUND: Blood-based biomarkers for gastric cancer risk stratification could facilitate targeting screening to people who will benefit from it most. The ABC Method, which stratifies individuals by their Helicobacter pylori infection and serum-diagnosed chronic atrophic gastritis status, is currently used in Japan for this purpose. Most gastric cancers are caused by chronic H. pylori infection, but few studies have explored the capability of antibody response to H. pylori proteins to predict gastric cancer risk in addition to established predictors. METHODS: We used the least absolute shrinkage and selection operator (Lasso) to build a predictive model of noncardia gastric adenocarcinoma risk from serum data on pepsinogen and antibody response to 13 H. pylori antigens as well as demographic and lifestyle factors from a large international study in East Asia. RESULTS: Our best model had a significantly (P < 0.001) higher AUC of 73.79% [95% confidence interval (CI), 70.86%-76.73%] than the ABC Method (68.75%; 95% CI, 65.91%-71.58%). At 75% specificity, the new model had greater sensitivity than the ABC Method (58.67% vs. 52.68%) as well as NPV (68.24% vs. 66.29%). CONCLUSIONS: Along with serologically defined chronic atrophic gastritis, antibody response to the H. pylori proteins HP 0305, HP 1564, and UreA can improve the prediction of gastric cancer risk. IMPACT: The new risk stratification model could help target more invasive gastric screening resources to individuals at high risk.


Assuntos
Adenocarcinoma , Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adenocarcinoma/complicações , Formação de Anticorpos , Infecções por Helicobacter/diagnóstico , Humanos , Pepsinogênio A , Fatores de Risco , Neoplasias Gástricas/diagnóstico
16.
Clin Gastroenterol Hepatol ; 20(10): 2218-2228.e2, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34624563

RESUMO

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of mortality among certain racial, ethnic, and immigrant groups in the United States (US). The majority of GCs are diagnosed at advanced stages, and overall survival remains poor. There exist no structured national strategies for GC prevention in the US. METHODS: On March 5-6, 2020 a summit of researchers, policy makers, public funders, and advocacy leaders was convened at Stanford University to address this critical healthcare disparity. After this summit, a writing group was formed to critically evaluate the effectiveness, potential benefits, and potential harms of methods of primary and secondary prevention through structured literature review. This article represents a consensus statement prepared by the writing group. RESULTS: The burden of GC is highly inequitably distributed in the US and disproportionately falls on Asian, African American, Hispanic, and American Indian/Alaskan Native populations. In randomized controlled trials, strategies of Helicobacter pylori testing and treatment have been demonstrated to reduce GC-specific mortality. In well-conducted observational and ecologic studies, strategies of endoscopic screening have been associated with reduced GC-specific mortality. Notably however, all randomized controlled trial data (for primary prevention) and the majority of observational data (for secondary prevention) are derived from non-US sources. CONCLUSIONS: There exist substantial, high-quality data supporting GC prevention derived from international studies. There is an urgent need for cancer prevention trials focused on high-risk immigrant and minority populations in the US. The authors offer recommendations on how strategies of primary and secondary prevention can be applied to the heterogeneous US population.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Etnicidade , Disparidades em Assistência à Saúde , Infecções por Helicobacter/epidemiologia , Hispânico ou Latino , Humanos , Prevenção Secundária , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Estados Unidos/epidemiologia
17.
Malawi Med J ; 34(1): 17-24, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-37265823

RESUMO

Introduction: Little is known about specific bacterial characteristics of Helicobacter pylori (H. pylori) infection influencing gastric carcinogenesis in Zambia. The aim of this study was to evaluate the associations between pre-selected H. pylori antibodies with gastric cancer, premalignant lesions and active gastritis. Methods: This was cross-sectional study with multiple comparisons of patients with gastric cancer (GC), gastric premalignant (GP) lesions and active or chronic gastritis. A fluorescent bead-based antibody multiplex serology assay was used to quantify antibodies to thirteen immunogenic H. pylori antigens. Logistic regression models were used to examine the associations. Results: Included were 295 patients with: 59 GC, 27 GP lesions, 48 active and 161 chronic gastritis. Overall, 257/295 (87%) were H. pylori positive. H. pylori seropositivity was not associated with sex, age, body mass index, socio-economic status, HIV infection, alcohol consumption or cigarette smoking (p-values all above 0.05). When compared to the patients with chronic gastritis, the presence of catalase and cinnamyl alcohol dehydrogenase (Cad) antibodies was positively associated with GP lesions (OR 3.53; 95% CI 1.52-8.17 and OR 2.47; 95% CI 1.08-5.67 respectively). However, seropositivity to Cad antibodies was significantly lower in GC patients (OR 0.28; 95% CI 0.09-0.83). Compared to chronic, active gastritis was significantly associated with (p<0.05) H. pylori sero-positivity (OR 9.46; 95% CI 1.25-71.52) and specific antibodies including cytotoxin-associated gene A, vacuolating cytotoxin A, Helicobacter cysteine-rich protein C, hypothetical protein HP0305 and outer membrane protein HP1564. Conclusions: Among Zambian patients seen at a single center, antibodies to H. pylori (CagA, VacA, Omp, HcpC, HP0305 and HpaA) were associated with active gastritis.


Assuntos
Gastrite , Infecções por HIV , Helicobacter pylori , Neoplasias Gástricas , Humanos , Helicobacter pylori/genética , Zâmbia/epidemiologia , Estudos Transversais , Universidades , Antígenos de Bactérias/genética , Gastrite/epidemiologia , Gastrite/microbiologia , Hospitais de Ensino
18.
J Nutr Sci ; 10: e95, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804516

RESUMO

Childhood trauma is strongly associated with poor health outcomes. Although many studies have found associations between adverse childhood experiences (ACEs), a well-established indicator of childhood trauma and diet-related health outcomes, few have explored the relationship between ACEs and diet quality, despite growing literature in epidemiology and neurobiology suggesting that childhood trauma has an important but poorly understood relationship with diet. Thus, we performed a cross-sectional study of the association of ACEs and adult diet quality in the Southern Community Cohort Study, a largely low-income and racially diverse population in the southeastern United States. We used ordinal logistic regression to estimate the association of ACEs with the Healthy Eating Index-2010 (HEI-10) score among 30 854 adults aged 40-79 enrolled from 2002 to 2009. Having experienced any ACE was associated with higher odds of worse HEI-10 among all (odds ratio (OR) 1⋅22; 95 % confidence interval (CI) 1⋅17, 1⋅27), and for all race-sex groups, and remained significant after adjustment for adult income. The increasing number of ACEs was also associated with increasing odds of a worse HEI-10 (OR for 4+ ACEs: 1⋅34; 95 % CI 1⋅27, 1⋅42). The association with worse HEI-10 score was especially strong for ACEs in the household dysfunction category, including having a family member in prison (OR 1⋅34; 95 % CI 1⋅25, 1⋅42) and parents divorced (OR 1⋅25; 95 % CI 1⋅20, 1⋅31). In summary, ACEs are associated with poor adult diet quality, independent of race, sex and adult income. Research is needed to explore whether trauma intervention strategies can impact adult diet quality.


Assuntos
Experiências Adversas da Infância , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Dieta , Humanos , Renda , Pessoa de Meia-Idade
19.
Cancer Epidemiol Biomarkers Prev ; 30(6): 1279-1282, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33737297

RESUMO

BACKGROUND: The association between prediagnostic antibody responses to Fusobacterium nucleatum (F. nucleatum) and subsequent risk of colorectal cancer is not established. METHODS: We conducted a nested case-control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States. RESULTS: Higher seroprevalence of any F. nucleatum antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight F. nucleatum proteins and colorectal cancer risk. CONCLUSIONS: Prediagnostic antibody responses to F. nucleatum proteins were not associated with the risk of colorectal cancer. IMPACT: Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining F. nucleatum in stool or tissue samples.


Assuntos
Anticorpos Antibacterianos/sangue , Neoplasias Colorretais/epidemiologia , Fusobacterium nucleatum/imunologia , Microbioma Gastrointestinal/imunologia , Idoso , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/imunologia , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco/estatística & dados numéricos , Estudos Soroepidemiológicos , Estados Unidos
20.
Gut Microbes ; 13(1): 1-13, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33382363

RESUMO

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, depletion of Hp0305 and Hp1564 significantly reduced levels of gastric cell-associated bacteria and markedly impaired the ability of H. pylori to stimulate pro-inflammatory cytokine production. Remarkably, our studies revealed that Hp1564 is required for translocation of the oncoprotein CagA into gastric epithelial cells. Our data provide experimental insight into the molecular mechanisms governing novel H. pylori pathogenicity factors that are strongly associated with gastric disease and highlight the potential of Hp0305 and Hp1564 as robust molecular tools that can improve identification of individuals that are highly susceptible to gastric cancer. We demonstrate that Hp0305 and Hp1564 augment H. pylori-mediated inflammation and gastric cancer risk by promoting key bacteria-gastric cell interactions that facilitate delivery of oncogenic microbial cargo to target cells. Thus, therapeutically targeting microbial interactions driven by Hp0305/Hp1564 may enable focused H. pylori eradication strategies to prevent development of gastric malignancies in high-risk populations.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Helicobacter pylori/patogenicidade , Lesões Pré-Cancerosas/microbiologia , Neoplasias Gástricas/microbiologia , Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Linhagem Celular , Citocinas/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Regulação Bacteriana da Expressão Gênica , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Lesões Pré-Cancerosas/sangue , Neoplasias Gástricas/sangue
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