Background:Chronic tissue damage induced by Helicobacter pylori (HP)-driven inflammation is considered the main risk of gastric carcinoma (GC). Epstein–Barr virus (EBV) infection has also been associated with GC. In this study, we aim to address the role of EBV in inflammatory GC precursor lesions and its added risk to HP infection.Methods:Antibodies against EBV, HP and the bacterial virulence factor CagA were measured in sera from 525 Mexican and Paraguayan patients with gastric disease. Gastric samples were characterised according to the updated Sydney classification and associations were estimated between antibody responses and severity of both tissue damage and inflammation.Results:We found significant associations (odd ratios and trends) between EBV and HP copositivity and premalignant lesions and intestinal-type GC. The EBV and HP coinfection was also significantly associated with increased infiltration of immune cells. No association was found between EBV and the less inflammation-driven diffuse-type GC.Conclusions:Our study suggests that EBV co-participates with HP to induce severe inflammation, increasing the risk of progression to intestinal-type GC.

Objective: The course of Helicobacter pylori infection and antibody response to CagA in patients with preneoplastic lesions and gastric cancer has not been thoroughly studied. We aimed to study H. pylori infection and antibody response to CagA in patients with non -atrophic gastritis, preneoplastic lesions, and gastric cancer. Methods: We studied patients attending one Oncology Hospital and one General Hospital in Mexico City. Diagnosis was based on endoscopy and histopathology in biopsies from six stomach regions. H. pylori infection was assessed by histology and serology, and antibodies against CagA were measured with immunoassay. Results: We included 618 patients, 368 with nonatrophic gastritis, 126 with precancerous lesions, and 65 with gastric cancer; in addition, 59 patients with duodenal ulcer were studied. Detection of infection and IgG against CagA had a significant increase from nonatrophic gastritis to mild and up to advanced stages of metaplasia (P < 0.05), followed by decreased infection and IgG to CagA in patients with gastric cancer (P < 0.05). However, infection and CagA antibodies were associated with young gastric cancer cases. Duodenal ulcer showed a significant association with infection detected by histology and serology, particularly among women, and a trend to associate with IgG to CagA. Conclusions: This study shows that H. pylori infection and CagA are risk markers for intestinal metaplasia. The prevalence of these risk markers decreases in gastric cancer, probably reflecting that infection decreases after advanced atrophy and metaplasia in the gastric mucosa. State of the disease, age, and sex influence the association of H. pylori infection and IgG response to CagA with gastroduodenal diseases. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2498-504)

Background: Many studies have analyzed the effect of behavioral risk factors such as common lifestyle patterns on the risk of disease. The aim of this study was to assess the effect of a healthy lifestyle index on the risk of breast cancer.Methods: A population-based case-control study was conducted in Mexico from 2004 to 2007. One thousand incident cases and 1,074 controls, matched to cases by 5-year age category, region, and health institution, participated in the study. A healthy lifestyle index was developed by means of principal components by using dietary pattern, physical activity, alcohol consumption, and tobacco smoking. A conditional logistic regression model was used to assess this association.Results: The healthy lifestyle index was defined as the combined effect of moderate and/or vigorousintensity physical activity, low consumption of fat, processed foods, refined cereals, complex sugars, and the avoidance of tobacco smoking and alcohol consumption. Results showed a protective effect on both pre-(OR ¼ 0.50, 95% CI: 0.29-0.84) and postmenopausal women (OR ¼ O.20, 95% CI: 0.11-0.37) when highest versus lowest index quintiles were compared.Conclusions: Healthy lifestyle was associated with a reduction in the odds of having breast cancer. Primary prevention of this disease should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles.Impact: This study is the first to assess a healthy lifestyle index in relation to the risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 20(5); 912-22. Ó2011 AACR.

This study shows the gastric epithelia of children respond to H. pylori infection by increasing the expression of TLR2, TLR4, TLR5, TLR9 and the cytokines IL-8, IL-10 and TNF-α.

Background: Polymorphisms in inflammation-related genes are factors associated with the development of gastroduodenal diseases in Helicobacter pylori-infected individuals. Materials and Methods: We aimed to analyze polymorphisms in HLA-DQ, together with other host and H. pylori variables as risk factors for precancerous and cancerous gastric lesions. 1052 individuals were studied, including nonatrophic gastritis (NAG), intestinal metaplasia (IM), gastric cancer (GC) or duodenal ulcer (DU) patients, and healthy volunteers. Results: Patients with alleles DQA*01:01 (OR 0.78), *01:02 (OR 0.29), *01:03 (OR 0.31), and DQB*02:01/02 (OR 0.40) showed a reduced risk for GC. A multivariate logistic regression analyses showed that patients with homozygote genotypes DQA1*03:01 (OR 7.27) and DQA1*04:01 (OR 8.99) and DQB1*05:01:01 (OR 12.04) were at significantly increased risk for GC. Multivariate analyses also demonstrated that age (OR>10.0) and gender (OR>2.0) were variables that influenced significantly the risk for GC, while H. pylori infection (OR>2.5) increased the risk for IM. Conclusions:We identified HLA-DQ alleles associated with IM and GC, and confirm that age, sex, and H. pylori infection are variables that also influence the risk for disease. The use of multiple markers, HLA-DQ alleles, age, sex, and H. pylori infection may be useful biomarkers for the early diagnosis of patients with IM and GC. K E Y W O R D Satrophic gastritis, gastric cancer, genetic polymorphism, H. pylori, HLA

Tumour Necrosis Factor (TNF) and Heat Shock Protein 70 (HSP70) are important molecules in inflammatory, infectious and tumoral processes. The genes codifying these molecules are polymorphic and certain alleles have been associated with susceptibility to disease. Gastric cancer is associated with an Helicobacter pylori‐induced chronic inflammatory response. The aim of this work was to analyze whether polymorphisms in inflammation‐related genes are associated with the development of gastric cancer. We studied 447 Mexican adult patients including 228 with non‐atrophic gastritis, 98 with intestinal metaplasia, 63 with gastric cancer and 58 with duodenal ulcer, and 132 asymptomatic individuals as well. DNA from peripheral white blood cells was typed for the Single Nucleotide Polymorphisms (SNPs) −308 of TNF‐α, +252 of TNF‐β, +190 of HSP70‐1, +1267 of HSP70‐2 and +2437 of HSP70‐HOM. Compared with the asymptomatic group, we found a significant association of TNF‐β*A and HSP70‐1*C alleles with gastric cancer (OR 5.69 and 3.76, respectively) and HSP70‐1*C with duodenal ulcer (OR 3.08). Genotype TNF‐β G/G showed a significant gene‐dose effect with gastric cancer (OR 0.09); whereas HSP70‐1 C/G showed significant association with both, gastric cancer (OR 13.31) and duodenal ulcer (OR 16.19). Polymorphisms in TNF and HSP70 showed a significant severity‐dose‐response as risk markers from preneoplastic lesions to gastric cancer in Mexican population, probably because of their association with an intense and sustained inflammatory response.

These results give consistency to diagnostic and therapeutic criteria for women with breast cancer who receive medical attention in Mexico, taking into consideration the characteristics of the tumor -such as extension, clinical stage and status of the lymph nodes- before making a decision as to the initial therapy.

Colonization of the gastric mucosa by Helicobacter pylori can lead to peptic ulcer and gastric adenocarcinoma. TLRs are signaling receptors involved in the recognition of microorganisms, and polymorphisms in their genes may influence the innate and adaptive immune response to H. pylori, affecting the clinical outcomes of the infection. We assessed the association between single nucleotide polymorphisms in TLR9 and TLR5 and gastroduodenal diseases. All patients were genotyped by allelic discrimination in regions 1174C>T and 1775A>G of TLR5 and -1237T>C and 2848G>A of TLR9. The 2848A allele of TLR9 was more frequent in duodenal ulcer and showed an association of risk with this pathology. Polymorphisms in TLR5 were not found to be associated with disease. Patients with polymorphisms in TLR9 and TLR5 expressed significantly lower levels of IL-1β and TNF-α, whereas polymorphisms in TLR5 also decreased the expression of IL-6 and IL-10. Our findings suggest that 2848G>A polymorphism in TLR9 increases the risk for the development of duodenal ulcer probably by modifying the inflammatory response to H. pylori infection. This is the first study to show an association of 2848A allele of TLR9 with duodenal ulcer and with altered expression of inflammatory cytokines in the gastric mucosa.