Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high-grade premalignant gastric lesions.

Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high-risk population groups.

Impact of invasive lobular carcinoma on long-term outcomes in Mexican breast cancer patients.

PURPOSE: The aim of this study was to compare the difference in disease-free survival (DFS) and overall survival (OS) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in our Hispanic population with breast cancer (BC). METHODS: We retrospectively analyzed a database of 4533 non-metastatic BC patients treated for BC at the National Cancer Institute in Mexico (INCan) between 2006 and 2016. We compared clinical characteristics, treatment and survival between women with invasive ductal and invasive lobular BC. We evaluated differences between survival curves with the log-rank test and used Cox's proportional hazards model for the multivariate analysis. RESULTS: Median follow-up time was 42.13 months (IQ25 25.2-IQ75 72.06). The median age was 50.9 years (IQ25 43.5-IQ75 59.8). DFS at 5 years was 80.8% for IDC versus 76.2% for ILC. 5 years OS was 88.7% for IDC versus 84.3% for ILC. Multivariate analysis showed that factors that negatively affected the 5-year DFS include: clinical stage III [hazard ratio (HR) 4.2, 95% CI 3.36-5.35; p < 0.001], triple negative phenotype (HR 1.4, 95% CI 1.08-1.81; p = 0.009), Ki67 ≥ 18 (HR 1.6, 95% CI 1.28-2.11; p < 0.001), and lobular histological type (HR 1.6, 95% CI 1.09-2.49; p = 0.017). Factors associated with a negative impact on OS were: clinical stage III (HR 4.5, 95% CI 3.15-6.54; p < 0.001), triple negative phenotype (HR 2.4, 95% CI 1.69-3.48; p < 0.001), and Ki67 ≥ 18% (HR 1.9, 95% CI 1.27-2.92; p = 0.02). CONCLUSION: Our results highlight the different biology of ILC and show that long-term prognosis in terms of DFS is not as favorable as previously reported.

Polymorphisms in IL-10 and TGF-ß gene promoter are associated with lower risk to gastric cancer in a Mexican population.

BACKGROUND: Helicobacter pylori infection is recognized as the main risk factor for gastric cancer (GC), the fifth most common neoplasia worldwide. H. pylori interacts with the immune system, disrupting the cytokine network and inducing chronic inflammation. This work aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in selected cytokine gene promoters and GC. METHODS: The study included 359 subjects, 125 GC patients, 109 intestinal metaplasia (IM) patients and 125 asymptomatic controls. DNA was extracted from white blood cells and nine SNPs in cytokine gene promoters were genotyped using predesigned 5'-endonulease assays. The association of the SNPs with IM and GC was evaluated using multinomial regression models. RESULTS: Both genotypes, TC (OR = 0.51, 95% CI = 0.27-0.98) and TT (OR = 0.42, 95% CI = 0.20-0.91) in the locus - 509 of the TGF-ß promoter were significantly associated with GC. The TT genotype in the locus - 819 of the IL-10 promoter was also significantly associated with GC (OR = 0.37, 95% CI = 0.17-0.81). No significant association was found with SNPs IL-4 -590 T/C (rs1800629), IL-6 -573G/C (rs1800796), IL-10 -592C/A (rs1800872), IL-10 -1082A/G (rs1800896), and, IFN-γ -1615C/T (rs2069705). CONCLUSIONS: SNPs in TGFß (- 509 C/T, rs1800469) and IL-10 (- 819 C/T, rs1800871) promoters were associated with a lower risk for GC in a Mexican population.

[Trends in the prevalence of ARIs and ADDs in early childhood and associated factors: Ensanut 2012 and 100k.] / Tendencias en la prevalencia de IRA y EDA en la primera infancia y factores asociados: Ensanut 2012 y 100k.

OBJECTIVE: To compare the prevalence of acute respiratory infections (ARI) and acute diarrheal disease (ADD) among children younger than five years of age living in localities with less than 100 000 inhabitants in Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 and Ensanut 100k (2018). In Ensanut 100k, we evaluate the associated factors. MATERIALS AND METHODS: Analysis of both surveys and of the Mexican Meteorological System. RESULTS: The estimated prevalence of ARI was 45.1% in 2012 vs. 32.9% in 2018. The decrease was significant among medium and high-income households. There were no changes in trends for ADD. Among households with lower EC, ARI was associated with roofing material, temperature, and rainy precipitation while ADD was associated with lack of piped water. CONCLUSIONS: The estimated prevalence of ARI has decreased in medium and high income households. Some households and weather conditions are associated with ARI and ADD.

OBJETIVO: Estimar y comparar las prevalencias de infec- ciones respiratorias agudas (IRA) y enfermedades diarreicas agudas (EDA) en menores de cinco años, residentes en localidades con menos de 100 000 habitantes, mediante análisis de la Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 y la Ensanut 100k (2018). En la Ensanut 100k se evaluaron los factores asociados con IRA y EDA. MATERIAL Y MÉTODOS: Análisis de ambas encuestas e información meteorológica de la Comisión Nacional del Agua. RESULTADOS: La prevalencia global estimada de IRA fue de 45.1% en 2012 vs. 32.9% en 2018. La disminución fue significativa en hogares de medianas y mayores capacidades económicas (CE). No se observaron cambios significativos para las EDA. En hogares con menores CE, las IRA se asociaron con material del techo y temperatura y las EDA con privación de agua entubada. CONCLUSIONES: Entre 2012 y 2018, la prevalencia de IRA disminuyó en hogares de medianas y mayores CE. Algunas condiciones de vivienda y meteorológicas se asocian con IRA y EDA.

Polymorphisms in HLA-DQ genes, together with age, sex, and Helicobacter pylori infection, as potential biomarkers for the early diagnosis of gastric cancer.

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.

Patterns of Adherence of Helicobacter pylori Clinical Isolates to Epithelial Cells, and its Association with Disease and with Virulence Factors.

BACKGROUND AND AIM: Adherence to the gastric epithelium is one of the most important steps of Helicobacter pylori to remain and cause disease. The aim of this study was to analyze whether H. pylori isolates from patients with different gastroduodenal diseases present differences in the pattern of adherence to gastric epithelial cells (AGS), in the ability to induce IL-8, and in the presence of virulence genes. METHODS: We tested 75 H. pylori strains isolated from nonatrophic gastritis, gastric cancer, and duodenal ulcer patients. The adhesion pattern and IL-8 induction were determined in AGS cells, and invasion of AGS cells was studied using a gentamicin protection assay. The IL-8 levels induced were determined by ELISA. RESULTS: Helicobacter pylori strains presented diffuse adherence (DA) and localized (LA) adherence patterns, similar to those described for enteropathogenic E. coli (EPEC), were observed in AGS cells. A DA pattern was observed in 57% and LA in 43% of the strains, and DA was more frequent in isolates from patients with gastric cancer (p = 0.044). Strains with a LA pattern induced higher levels of IL-8 (p = 0.042) in AGS cells. CONCLUSION: The adherence pattern was not associated with neither invasiveness nor with the presence of virulence genes. Our study shows that H. pylori strains present adherence patterns to AGS cells resembling those observed in EPEC and that these patterns may be associated with disease and with activity on AGS cells.

Sugar-Sweetened Beverages Consumption and Breast Cancer in Premenopausal and Postmenopausal Women.

BACKGROUND: The consumption of sugar-sweetened beverages (SSB), of which Mexico is a large consumer, has been associated with the risk of breast cancer. We assessed the association between SSBs consumption and breast cancer risk in pre- and postmenopausal women. METHODS: We performed a multicenter population-based case-control study in Mexico City, Monterrey, and Veracruz. We recruited 1,000 cases and 1,074 controls; all participants were pre- or postmenopausal women between 35 and 69 years of age. Diet before symptoms onset was assessed using a food frequency questionnaire. We conducted a multivariable-adjusted conditional logistic regression analysis stratified by menopausal status. RESULTS: For premenopausal women, after adjusting for matching characteristics, total energy intake and all potential confounders, the odds of having breast cancer in women who drank one or more SSBs servings per day showed 1.78 times the odds of those who drank one or fewer SSBs servings per month [OR = 1.78; 95% confidence interval (CI), 1.06-3.01]. For postmenopausal women, the corresponding model was not statistically significant (OR = 1.38, 95% CI, 0.84-2.25). We also observed higher consumption of SSBs among pre- than in postmenopausal women (23.3% and 17.4%, respectively among controls in the highest consumption category (≥1 per day). CONCLUSIONS: Our results suggest that SSBs consumption increases the risk of developing breast cancer, particularly in premenopausal women. IMPACT: Given the consumption of SSBs, of which Mexico is a large consumer, these results can support public policies to discourage the consumption of SSBs.

Genomic and phenotypic studies among Clostridioides difficile isolates show a high prevalence of clade 2 and great diversity in clinical isolates from Mexican adults and children with healthcare-associated diarrhea.

Clostridioides difficile (C. difficile) is widely distributed in the intestinal tract of humans, animals, and in the environment. It is the most common cause of diarrhea associated with the use of antimicrobials in humans and among the most common healthcare-associated infections worldwide. Its pathogenesis is mainly due to the production of toxin A (TcdA), toxin B (TcdB), and a binary toxin (CDT), whose genetic variants may be associated with disease severity. We studied genetic diversity in 39 C. difficile isolates from adults and children attended at two Mexican hospitals, using different gene and genome typing methods and investigated their association with in vitro expression of toxins. Whole-genome sequencing in 39 toxigenic C. difficile isolates were used for multilocus sequence typing, tcdA, and tcdB typing sequence type, and phylogenetic analysis. Strains were grown in broth media, and expression of toxin genes was measured by real-time PCR and cytotoxicity in cell-culture assays. Clustering of strains by genome-wide phylogeny matched clade classification, forming different subclusters within each clade. The toxin profile tcdA+/tcdB+/cdt+ and clade 2/ST1 were the most prevalent among isolates from children and adults. Isolates presented two TcdA and three TcdB subtypes, of which TcdA2 and TcdB2 were more prevalent. Prevalent clades and toxin subtypes in strains from children differed from those in adult strains. Toxin gene expression or cytotoxicity was not associated with genotyping or toxin subtypes. In conclusion, genomic and phenotypic analysis shows high diversity among C. difficile isolates from patients with healthcare-associated diarrhea. IMPORTANCE: Clostridioides difficile is a toxin-producing bacterial pathogen recognized as the most common cause of diarrhea acquired primarily in healthcare settings. This bacterial species is diverse; its global population has been divided into five different clades using multilocus sequence typing, and strains may express different toxin subtypes that may be related to the clades and, importantly, to the severity and progression of disease. Genotyping of children strains differed from adults suggesting toxins might present a reduced toxicity. We studied extensively cytotoxicity, expression of toxins, whole genome phylogeny, and toxin typing in clinical C. difficile isolates. Most isolates presented a tcdA+/ tcdB+/cdt+ pattern, with high diversity in cytotoxicity and clade 2/ST1 was the most prevalent. However, they all had the same TcdA2/TcdB2 toxin subtype. Advances in genomics and bioinformatics tools offer the opportunity to understand the virulence of C. difficile better and find markers for better clinical use.

Toll-like receptors and cytokines are upregulated during Helicobacter pylori infection in children.

BACKGROUND AND AIM: Helicobacter pylori infection is mainly acquired during childhood, and establishes a chronic infection that may lead to peptic ulcer or gastric cancer during adulthood. Toll-like receptors (TLRs) are expressed by distinct cell types throughout the gastrointestinal tract, and play an important role in regulation of the innate immune response. Few works have addressed TLRs expression in gastric epithelia of adults, and scarce studies have done it in children. The aim of this work was to analyze the expression of TLR2, TLR4, TLR5, TLR9, and IL-8, IL-10 and TNF-α in the gastric mucosa of children with and without H. pylori infection. METHODS: Gastric biopsies were collected by endoscopy from 50 children with recurrent abdominal pain, 25 with H. pylori infection and 25 without infection. In the gastric biopsies the expression of TLRs and cytokines was studied by immunohistochemistry, and the degree of mucosal inflammation was determined using the Sydney system. RESULTS: We found that H. pylori infection was associated with a significant increased expression of TLRs 2, 4, 5 and 9, although expression varied between surface epithelia and glands. Epithelial cells expressing IL-8, IL-10 and TNF-α were increased in gastric mucosa of children with H. pylori infection. CONCLUSION: 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.

Analysis of the polymorphisms EGFR-r521K and ERBB2-I655V in Mexican patients with gastric cancer and premalignant gastric lesions.

The proto-oncogenes epidermal growth factor receptor (EGFR) and erythroblastic leukemia viral oncogene homolog 2 (ERBB2), are involved in the development of diverse malignant tumors, including gastric cancer. We analyzed the association of SNPs EGFR-R521K and ERBB2-I655V with gastric cancer and premalignant gastric lesions in Mexican patients. Through restriction fragment length polymorphisms, we analyze both SNPs in the DNA from 155 patients with gastric cancer and premalignant gastric lesions, 121 controls, and 103 people from the Mexican general population. The frequencies of both SNPs did not differ significantly between any of the groups (chi2 p = NS); Odds ratio analysis showed that the alleles EGFR-521K and ERBB2-655V were not related to gastric cancer or premalignant gastric lesions in the Mexican population. Our data suggest that the EGFR-R521K and ERBB2-I655V polymorphisms are not suitable as markers for identifying individuals with a higher risk for developing gastric cancer in our population.

Phylogenetic origin of Helicobacter pylori pathogenicity island and risk of stomach cancer and high-grade premalignant gastric lesions.

Infection by Helicobacter pylori (Hp) has been causally linked to risk of gastric cancer (GC). The coevolution of Hp and humans shaped the risk of GC as our species left Africa and migrated to the other continents. Latin America (LatAm) is a high GC incidence region where Hp evolved uniquely in the 500 years since European colonization. Differential virulence of the Hp cagA -pathogenicity island (cagPAI) by ancestral origin has been reported. We hypothesized that Hp phylogenetic origin might play a role in determining GC risk in LatAm. We used genotypes of 50 Hp genetic variants mapping to the Hp cagPAI, studied in 1220 subjects from Venezuela, Colombia, Mexico and Paraguay, who were infected with cagA-positive Hp, including 150 GC, 177 high-grade premalignant lesions (HGPMLs) and 893 low-grade premalignant lesions. We estimated the phylogenetic origin of Hp cagPAI in all study subjects by use of the STRUCTURE software and principal component analysis (PCA) and tested whether the estimated African ancestry percentage was associated with the risk of GC or HGPML. African ancestral component estimates by STRUCTURE and PCA were highly correlated. STRUCTURE-based African origin estimate was not significantly associated with the risk of HGPML, but it was inversely associated with GC risk: the OR associated with the continuous values of African component was 0.09 (95% CI, 0.01-0.85; P = 0.035). Similar trends were observed for GC with PCA-based estimates, but the association was not statistically significant. These results suggest that Hp ancestral origin may play a role in gastric carcinogenesis.

TAS2R38 polymorphisms, Helicobacter pylori infection and susceptibility to gastric cancer and premalignant gastric lesions.

BACKGROUND: Gastric cancer is worldwide the fourth more common cancer type by incidence, and the third by mortality. We analyzed three missense variants of TAS2R38 gene: rs713598 (A49P), rs1726866 (V262A), and rs10246939 (I296V). These variants and their combination in haplotypes (proline, alanine and valine/tasters or alanine, valine and isoleucine/nontasters) and diplotypes are responsible for individual differences in bitter perception. The single-nucleotide polymorphisms and the related phenotypes are known to be associated with susceptibility to Gram-negative bacterial infections, such as Helicobacter pylori , and with risk of various cancer types. An association between intermediate tasters (as defined by TAS2R38 diplotypes) and increased risk of gastric cancer was reported in a Korean population. METHODS: We analyzed 2616 individuals of Latin American origin, representing the whole spectrum of lesions from gastritis to gastric cancer. RESULTS: Comparing cancer cases vs. noncancers we observed a decrease in risk associated with heterozygous carriers of rs10246939 ( P = 0.006) and rs1726866 ( P = 0.003) when compared with homozygotes of the more common allele. Also, the analysis of diplotypes/phenotypes reflected the same association, with super-tasters showing a borderline increased risk of developing gastric cancer compared to medium-tasters [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.04-2.56; P = 0.033]. Also, nontasters showed an increased risk when compared to medium-tasters although not reaching statistical significance (OR = 1.58; 95% CI, 0.80-2.87; P = 0.203). We also tested the interactions between the TAS2R38 genotypes and H. pylori cagA status in a subset of samples and found no interaction. CONCLUSION: In conclusion, our results suggest only a modest contribution of TAS2R38 gene genetic variability in gastric cancer etiology.

Energy homeostasis genes modify the association between serum concentrations of IGF-1 and IGFBP-3 and breast cancer risk.

Breast cancer is a multifactorial disease in which the interplay among multiple risk factors remains unclear. Energy homeostasis genes play an important role in carcinogenesis and their interactions with the serum concentrations of IGF-1 and IGFBP-3 on the risk of breast cancer have not yet been investigated. The aim of this study was to assess the modifying effect of the genetic variation in some energy homeostasis genes on the association of serum concentrations of IGF-1 and IGFBP-3 with breast cancer risk. We analyzed 78 SNPs from 10 energy homeostasis genes in premenopausal women from the 4-Corner's Breast Cancer Study (61 cases and 155 controls) and the Mexico Breast Cancer Study (204 cases and 282 controls). After data harmonization, 71 SNPs in HWE were included for interaction analysis. Two SNPs in two genes (MBOAT rs13272159 and NPY rs16131) showed an effect modification on the association between IGF-1 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). In addition, five SNPs in three genes (ADIPOQ rs182052, rs822391 and rs7649121, CARTPT rs3846659, and LEPR rs12059300) had an effect modification on the association between IGFBP-3 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). Our findings showed that variants of energy homeostasis genes modified the association between the IGF-1 or IGFBP-3 serum concentration and breast cancer risk in premenopausal women. These findings contribute to a better understanding of this multifactorial pathology.

Association of circulating VacA-neutralizing antibodies with gastric cancer and duodenal ulcer.

OBJECTIVE: To study the association between anti-VacA antibodies and pre-neoplastic lesions (IM), gastric cancer (GC), and duodenal ulcer (DU). METHODS: A case-control study that included 347 patients, 90 with IM, 60 with GC, 52 with DU, and 145 with non-atrophic gastritis was conducted. For the analysis, a polytomous logistic regression models were used. Anti-VacA antibodies were identified in sera from these patients, either by Western blot assay (WB), using antigens produced by H. pylori s1m1 strain, or by neutralization assay challenging HeLa cells with H. pylori VacA s1m1 cytotoxin. RESULTS: Results of the WB assay showed no association between WB-anti-VacA antibodies and gastroduodenal diseases. In contrast, when antibodies that neutralize VacA cytotoxic activity were studied, a significant association was found with IM (OR 2.7, 95% CI 1.4-5.1) and DU (OR 2.3, 95% CI 1.1-4.9) and an even stronger association with GC (OR 3.9, 95% CI 1.8-8.5). A significant association with histological subtypes of GC (diffuse and intestinal) and of IM (complete and incomplete) was also found. In addition, the association showed a significant dose-response effect in the case of GC, but not of DU or IM. These associations did not change substantially after adjustment for confounding factors. MAIN CONCLUSION: This study showed that VacA-neutralizing antibodies are significantly associated with gastroduodenal diseases, especially GC, and that they might be used as risk markers of GC and DU.

Polymorphisms in TNF and HSP-70 show a significant association with gastric cancer and duodenal ulcer.

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-alpha, +252 of TNF-beta, +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-beta*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-beta 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.

[Reproducibility of histopathologic diagnosis of precursor lesions of gastric carcinoma in three Latin American countries]. / Reproducibilidad del diagnóstico histopatológico de lesiones precursoras del carcinoma gástrico en tres países latinoamericanos.

OBJECTIVE: The aim was to evaluate the concordance in the diagnosis of precursor lesions of intestinal-type gastric carcinoma among observers with different levels of experience. MATERIAL AND METHODS: Gastric biopsies from 1 056 cases were studied: 341 from Colombia, 382 from Mexico, and 333 from Paraguay. Pathologists without experience (A) and with experience (B) in gastrointestinal pathology, as well as experts working in an international reference center (C) participated in the diagnosis of each case. RESULTS: The concordance (k) between pathologists with experience and those without was poor for the diagnosis of atrophic gastritis (k=0.04 to 0.12) and dysplasia (k=0.11 to 0.05), and good for the diagnosis of intestinal metaplasia (k=0.52 to 0.58). Supervision of pathologists without experience by those with experience remarkably improved the concordance in the diagnosis of atrophic gastritis (k=0.65) and intestinal metaplasia (k=0.91), and to a lesser degree, of dysplasia (k=0.28). The concordance among experts before and after the consensus meeting showed no variation in the diagnosis of atrophic gastritis (k=0.57); the concordance varied from good to excellent in the diagnosis of intestinal metaplasia (k=0.67 to 0.81) and from poor to good in that of dysplasia (k=0.18 to 0.66). CONCLUSION: The greatest differences arose in the diagnosis of chronic atrophic gastritis and dysplasia. The interobserver concordance depended on the experience of the observer and the consensus reading.

Risk factors for gastric precancerous and cancers lesions in Latin American counties with difference gastric cancer risk.

OBJECTIVE: To evaluate the risk factors associated with pre-neoplastic lesions and gastric cancer in countries with different cancer risk in Latin America. METHODS: 1222 questionnaires of risk factors related to pre-neoplastic lesions and gastric cancer were obtained from patients from Mexico (N = 559), Colombia (N = 461) and Paraguay (N = 202), who were treated at the gastroenterology or oncology service of participant hospitals. In addition, biopsies specimens to establish histological diagnosis and blood to detect IgG antibodies against Helicobacter-pylori (H. pylori) whole-cell antigens and CagA protein using an ELISA were collected. These consisted of 205 gastric cancer, 379 pre-neoplastic (intestinal metaplasia (IM) / atrophic gastritis) and 638 control (normal /non-atrophic gastritis) cases. The odds ratio (OR) and 95% confidence intervals (CI) associated with potential risk factors were estimated by polynomial logistic regression model. RESULTS: Seropositivity to H. pylori was associated with risk of pre-neoplastic lesions, with OR = 1.9 (CI 95% 1.2-2.9; p = 0.006). Grain / cereal intake (OR = 1.6, 95% CI 1.0-2.5 ; p = 0.049) and egg intake (OR = 1.7 95% CI 1.1-2.6 ; p = 0.021) were related to gastric cancer. Among, people who did not developed gastric cancer, smoking more than five cigarette per day had the highest risk of being infected by H. pylori (OR = 1.9; CI 95% 1.1-3.3 ; p = 0.028). CONCLUSION: The present study in Latin American countries confirmed that similar environmental factors such as smoking and grain/cereal consumption were associated with H. pylori infection and its induced gastric lesions as reported in other regions where dominant H. pylori strains differ.

Detection of Epstein-Barr Virus DNA in Gastric Biopsies of Pediatric Patients with Dyspepsia.

In this study, we assessed the presence of Epstein-Barr virus (EBV) in gastric samples derived from pediatric patients with dyspeptic symptoms, aiming to understand whether EBV participates in the development of early gastric lesions influencing chronic inflammation, in conjunction with the Helicobacter pylori (Hp) bacterium. We analyzed EBV load in 236 gastric biopsies derived from 186 pediatric patients with chronic dyspepsia and compared it with EBV serology, Hp load and serology, and with immune cell infiltration. We found that 7.5% of patients were positive for EBV load, ranging from 240 to 29,685 genomic copies/µg of DNA. Hp genomic sequences were found in 24.7% of patients. EBV positive samples did not correlate with Hp status and were characterized by absent to moderate immune cell infiltration. To our knowledge, this is the first study addressing EBV load in the stomach in a large cohort of pediatric patients with dyspeptic symptoms, providing evidence of EBV localization in the gastric mucosa in early inflammatory lesions. The lack of correlation between EBV and both Hp infection and inflammation is perhaps explained by independent pathogenic mechanisms or because of the randomness of the gastritis sampling. This is also supported by a moderate association between EBV load and serology.

Synergistic action of folate intake and testosterone associated with breast cancer risk.

The amount of irreparable DNA damage is a function of the rate of cell division, and the association between sex hormones and the risk of breast cancer has been explained by an increase in cell division. Folate intake insufficiency leads to disturbances in DNA replication and DNA repair. We hypothesized that folate intake insufficiency and high serum concentrations of sex hormones act synergistically on the risk of breast cancer. The aim of this study was to investigate the interaction between sex hormones (exposure of interest A) and dietary folate intake (exposure of interest B) on the risk of breast cancer. We included 342 breast cancer primary postmenopausal cases and 294 controls obtained from a large population-based case-control study. Multiple conditional logistic regression models were used for the analysis and interactions were tested. The joint effect of the lowest dietary folate intake (T1 < 259.40 mg/d) and the highest serum concentration of testosterone (T3 ≥ 0.410 on the risk of breast cancer was odds ratio = 9.18 (95% confidence interval 2.56-32.88) when compared to the lowest-risk category, namely, the group of women with the highest dietary folate intake (T3 > 381.29 mg/d) and the lowest serum concentration of testosterone (T1 ≤ 0.25 pg/mL). There were some indications that the estimated join effect was greater than the product of the estimated effects alone (P = .001). These findings have important public health implications with respect to reducing the risk of the most frequent cancer in women worldwide.

Age and severity of mucosal lesions influence the performance of serologic markers in Helicobacter pylori-associated gastroduodenal pathologies.

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 non-atrophic 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 non-atrophic 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.