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.

Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas.

For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations.

Correction: Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas.

[This corrects the article DOI: 10.1371/journal.pgen.1006546.].

Altered HLA class I and HLA-G expression is associated with IL-10 expression in patients with cervical cancer.

Although high-risk human papillomaviruses (HPVs) are an important risk factor in the etiopathogenesis of cervical cancer, increasing evidence suggests that the ability to avoid immune surveillance seems to be linked to the transforming potential of HPV and a rapid progression to cancer. In other cancer models, IL-10 contributes to impair anti-tumor immune response either by downregulating human leukocyte antigen Class I (HLA-I) expression or by increasing HLA-G expression. To comprehend how these alterations could contribute to evasion of immune surveillance in cervical cancer, we analyzed HLA-I, HLA-G and IL-10 expressions by immunohistochemistry in 63 biopsies from patients with cervical intraepithelial neoplasia III (CIN-III) and cervical cancer. Immunohistochemistry showed absent or weak HLA-I expression in 50/59 cases. In these cases, a high percentage had loss of heterozygosis. IL-10 and HLA-G expression were observed in 46.6 and 27.6% of cases, respectively. Concurrent upregulation of IL-10 was found in 87.5% of HLA-G positive cases (p = 0.000). Similarly, a significant association between IL-10 expression and HLA-I downregulation was found (p = 0.028). Finally, we observed higher HLA-G expression in patients with HLA-I downregulation than in those with normal HLA-I expression (p = 0.004). Our results suggest that, in cervical cancer, the IL-10 expression may induce an immunosuppressive environment by upregulating HLA-G expression and downregulating HLA class I expression.

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.

The OLGA-OLGIM staging and the interobserver agreement for gastritis and preneoplastic lesion screening: a cross-sectional study.

Stomach cancer (SC) incidence and mortality are relevant public health issues worldwide. In Colombia, screening for preneoplastic lesions (PNL) and the presence of H. pylori is not routinely performed. Therefore, the aim of this study was to evaluate OLGA-OLGIM staging and the interobserver agreement in gastritis and preneoplastic lesions in patients with gastroduodenal symptoms from Colombia. A cross-sectional study was conducted in 272 patients with gastroduodenal symptoms. Gastric biopsies were taken following the Updated Sydney System with the OLGA-OLGIM classification, and the results were evaluated by two pathologists. Chronic gastritis and PNL were reported in 76% and 24% of the patients, respectively. Furthermore, 25% of the patients with PNL displayed gastric atrophy (GA) and 75% intestinal metaplasia (IM). Agreement in the histopathological reading for IM was good, whereas for OLGA was variable, and for the H. pylori quantity was poor. OLGA-OLGIM stages 0-II were the most frequent (96%), while stage III (4%) and SC (4%) were the least frequent. Age and coffee consumption were associated with a higher prevalence of PNL. This work determined that 4% of the population is at high risk of developing SC and would benefit from follow-up studies. Reinforcement of training programs to improve the agreement in histopathology readings is required.

[Association of interleukin-1 genetic polymorphism and CagA positive Helicobacter pylori with gastric cancer in Colombia]. / Asociación de los polimorfismos IL-1B-511 e IL-1RN y Helicobacter pylori CagA positivo con cáncer gástrico en una zona de riesgo alto en Colombia.

BACKGROUND: There is an association of interleukin (IL)1B polymorphism with gastric cancer risk. However systematic reviews of the existing evidence have shown that such association varies across populations with different genetic ancestry. AIM: To evaluate the association of IL-1B-511 and IL-1RN polymorphism and Helicobacter pylori IgG antibodies CagA, with gastric cancer in two Colombian cities located in a high risk area for gastric cancer. MATERIAL AND METHODS: A case-control study including 46 gastric cancer cases and 99 controls with non-atrophic gastritis from a high risk zone for gastric cancer. Polymorphism genotyping was carried out by polymerase chain reaction (PCR) and IgG CagA status by ELISA. RESULTS: IgG CagA seropositive individuals had an increased gastric cancer risk (odds ratio (OR) = 11.56; 95% confidence intervals (CI) 2.62-50.91 in Tunja and OR = 19.66, 95%CI 0.98-395 in Bogotá). IL-1B-511TT carriers in Tunja had increased risk of gastric cancer (OR = 11.31; 95%CI 1.20-106.54)), while IL-1RN*2 alelle carriers in Bogotá showed an inverse association with gastric cancer risk (OR = 0.03; 95%CI 0.01-0.65). CONCLUSIONS: This study adds evidence to the positive association of Helicobacter pylori CagA positive strains with non-cardial gastric cancer etiology. There is a possible heterogeneity in the association of IL-1B gene polymorphism with cancer, in populations of similar ethnic background and settled in the same risk area.

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.

Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer.

Helicobacter pylori (HP) colonizes the human stomach and induces acute gastritis, peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Increased virulence in HP isolates derives from harboring the cag (cytotoxin-associated genes) pathogenicity island (cagPAI). We analyzed the microvariants in cagPAI genes with the hypothesis that they may play an important role in determining HP virulence. We tested DNAs from cagA positive patients HP isolates; a total of 74 patients with chronic gastritis (CG, N = 37), intestinal metaplasia (IM, N = 21) or gastric cancer (GC, N = 16) from Mexico and Colombia. We selected 520 non-synonymous variants with at least 7.5% frequency in the original sequence outputs or with a minimum of 5 isolates with minor allele. After adjustment for multiple comparisons, no variants were statistically significantly associated with IM or GC. However, 19 non-synonymous showed conventional P-values < 0.05 comparing the frequency of the alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC; 12 of these showed a significant correlation with the severity of the disease. The present study revealed that several cagPAI genes from Latin American Western HP strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. However, none of the associations remained statistically significant after adjustment for multiple comparison.

Increase of human papillomavirus-16 E7-specific T helper type 1 response in peripheral blood of cervical cancer patients after radiotherapy.

It has been suggested that tumour cell lysis by gamma-radiation induces a tumoral antigen release eliciting an immune response. It is not clear how a specific immune response in cervical cancer patients is developed after radiotherapy. This study is an attempt to investigate the role of the human papillomavirus type 16 (HPV-16) E7-specific T helper response before and after radiotherapy. Lymphocytes were isolated from 32 cervical cancer patients before and after radiotherapy and from 16 healthy women. They were stimulated for 12 hr with autologous HPV-16 E7-pulsed monocyte-derived dendritic cells or directly with HPV-16 E7 synthetic peptides: E7(51-70), E7(65-84) and E7(79-98). The cells were stained for CD4, CD69, intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) cytokines and analysed by flow cytometry. A specific CD4(+) CD69(+) IFN-gamma(+) immune response against HPV-16 E7(79-98) peptide was observed in 10 of 14 patients (71.4%) after treatment, compared with 4 of 14 (28.5%) before radiotherapy (P = 0.039); however, this response was not associated with a successful clinical response. Before treatment, 5 of 31 patients showed a HPV-16 E7(79-98)-specific T helper type 2 (Th2) response. Interestingly, this response was significantly associated with a decrease in disease-free survival (P = 0.027). These results suggest that a Th2-type cellular response could be useful as a predictor of recurrence and poor prognosis. An increase of the HPV-specific immune response was observed after radiotherapy; however, it is not enough to control completely the disease after treatment. Our results support that the E7-specific T-cell IFN-gamma response in cervical cancer patients, rather than reflecting the host's capability of controlling tumour growth, might be an indicator for disease severity.

Potential Role of Biofilm Formation in the Development of Digestive Tract Cancer With Special Reference to Helicobacter pylori Infection.

Bacteria are highly social organisms that communicate via signaling molecules and can assume a multicellular lifestyle to build biofilm communities. Until recently, complications from biofilm-associated infection have been primarily ascribed to increased bacterial resistance to antibiotics and host immune evasion, leading to persistent infection. In this theory and hypothesis article we present a relatively new argument that biofilm formation has potential etiological role in the development of digestive tract cancer. First, we summarize recent new findings suggesting the potential link between bacterial biofilm and various types of cancer to build the foundation of our hypothesis. To date, evidence has been particularly convincing for colorectal cancer and its precursor, i.e., polyps, pointing to several key individual bacterial species, such as Bacteroides fragilis, Fusobacterium nucleatum, and Streptococcus gallolyticus subsp. Gallolyticus. Then, we further extend this hypothesis to one of the most common bacterial infection in humans, Helicobacter pylori (Hp), which is considered a major cause of gastric cancer. Thus far, there has been no direct evidence linking in vivo Hp gastric biofilm formation to gastric carcinogenesis. Yet, we synthesize the information to support an argument that biofilm associated-Hp is potentially more carcinogenic, summarizing biological characteristics of biofilm-associated bacteria. We also discuss mechanistic pathways as to how Hp or other biofilm-associated bacteria control biofilm formation and highlight recent findings on Hp genes that influence biofilm formation, which may lead to strain variability in biofilm formation. This knowledge may open a possibility of developing targeted intervention. We conclude, however, that this field is still in its infancy. To test the hypothesis rigorously and to link it ultimately to gastric pathologies (e.g., premalignant lesions and cancer), studies are needed to learn more about Hp biofilms, such as compositions and biological properties of extracellular polymeric substance (EPS), presence of non-Hp microbiome and geographical distribution of biofilms in relation to gastric gland types and structures. Identification of specific Hp strains with enhanced biofilm formation would be helpful not only for screening patients at high risk for sequelae from Hp infection, but also for development of new antibiotics to avoid resistance, regardless of its association with gastric cancer.

Rapid evolution of the Helicobacter pylori AlpA adhesin in a high gastric cancer risk region from Colombia.

To be able to survive, Helicobacter pylori must adhere to the gastric epithelial cells of its human host. For this purpose, the bacterium employs an array of adhesins, for example, AlpA. The adhesin AlpA has been proposed as a major adhesin because of its critical role in human stomach colonization. Therefore, understanding how AlpA evolved could be important for the development of new diagnostic strategies. However, the genetic variation and microevolutionary patterns of alpA have not been described in Colombia. The study aim was to describe the variation patterns and microevolutionary process of alpA in Colombian clinical isolates of H. pylori. The existing polymorphisms, which are deviations from the neutral model of molecular evolution, and the genetic differentiation of the alpA gene from Colombian clinical isolates of H. pylori were determined. The analysis shows that gene conversion and purifying selection have shaped the evolution of three different variants of alpA in Colombia.

Insulin-like growth factor system gene expression in cervical scrapes from women with squamous intraepithelial lesions and cervical cancer.

BACKGROUND: There is ample evidence that the insulin-like growth factors (IGF) system is involved in the development of several types of cancer. The aim of this study was to evaluate the expression levels of IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3) and IGF-I receptor (IGF-IR) in exfoliated cervical cells in cervical carcinogenesis. METHODS: mRNA levels of IGF-I, IGF-II, IGFBP-3 and IGF-IR were assessed by real-time PCR in 105 cervical scrapes obtained from 16 patients diagnosed with low-grade squamous intraepithelial lesions (LSIL), 24 with high-grade SIL (HSIL), 23 with cervical cancer, and 42 from controls with normal Papanicolau (Pap) test. RESULTS: IGF-I mRNA levels were very low and no significant differences were seen between control and other groups. IGF-II mRNA levels were significantly lower in LSIL than in control group (median [arbitrary units]: 0.38 vs. 2.42, P=0.006) but its expression in HSIL and cervical cancer was similar to the one observed in controls. IGFBP-3 mRNA levels were significantly lower in cancer than in controls (median [arbitrary units]: 0.43 vs. 0.73, P=0.03). We observed a decrease in IGF-IR gene expression as the SIL degree increased (median for controls, LSIL, HSIL, and cervical carcinoma [arbitrary units]: 31.24, 9.08, 8.95, and 3.56, respectively). IGF-IR mRNA levels were significantly lower in HSIL and cervical cancer in comparison with controls (P=0.043 and P<0.001, respectively). CONCLUSIONS: The present observations suggest that a reduced expression of IGFBP-3 and IGF-IR can be associated with progression to cervical cancer; the specific role played by the IGF-IR in this process remains unclear.

Phylogenomics of Colombian Helicobacter pylori isolates.

BACKGROUND: During the Spanish colonisation of South America, African slaves and Europeans arrived in the continent with their corresponding load of pathogens, including Helicobacter pylori. Colombian strains have been clustered with the hpEurope population and with the hspWestAfrica subpopulation in multilocus sequence typing (MLST) studies. However, ancestry studies have revealed the presence of population components specific to H. pylori in Colombia. The aim of this study was to perform a thorough phylogenomic analysis to describe the evolution of the Colombian urban H. pylori isolates. RESULTS: A total of 115 genomes of H. pylori were sequenced with Illumina technology from H. pylori isolates obtained in Colombia in a region of high risk for gastric cancer. The genomes were assembled, annotated and underwent phylogenomic analysis with 36 reference strains. Additionally, population differentiation analyses were performed for two bacterial genes. The phylogenetic tree revealed clustering of the Colombian strains with hspWestAfrica and hpEurope, along with three clades formed exclusively by Colombian strains, suggesting the presence of independent evolutionary lines for Colombia. Additionally, the nucleotide diversity of horB and vacA genes from Colombian isolates was lower than in the reference strains and showed a significant genetic differentiation supporting the hypothesis of independent clades with recent evolution. CONCLUSIONS: The presence of specific lineages suggest the existence of an hspColombia subtype that emerged from a small and relatively isolated ancestral population that accompanied crossbreeding of human population in Colombia.

Serum levels of insulin-like growth factor-I and -II and insulin-like growth factor binding protein 3 in women with squamous intraepithelial lesions and cervical cancer.

INTRODUCTION: Pap smear has limitations as a screening test for cervical cancer. A marker that allows the identification of women who are at risk of developing cervical cancer would be useful for its prevention. A growing number of studies have demonstrated an association between insulin-like growth factors (IGF) serum levels and increased risk for various cancers. Objective. To assess whether circulating IGF-I, IGF-II, or IGF binding protein 3 (IGFBP-3) were associated with cervical cancer and low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL). MATERIALS AND METHODS: Serum levels of IGF-I, IGF-II and IGFBP-3 were measured by ELISA. Three groups of cases were analyzed: LSIL (n = 37), HSIL (n = 57), and cervical cancer (n = 41). For each case, two controls, matched by age, were included. Control subjects were women with normal, HPV-DNA-negative Pap smear. RESULTS: Significantly lower values of IGF-I (83.9 ng/ml versus 126.6 ng/ml, p < 0.001) and IGF-I:IGFBP-3 molar ratio (0.094 versus 0.137, p < 0.001) were observed among cancer cases, as compared to their control group. Women in the highest quartile of IGF-I and IGF-I:IGFBP-3 molar ratio were at an 80% (OR = 0.2, 95% CI [0.06-0.61]) and a 77% (OR = 0.23, 95% CI [0.07-0.73]) lower risk of cervical cancer, respectively, compared with women in the corresponding reference category. CONCLUSIONS: These data suggest that low values of IGF-I and IGF-I:IGFBP-3 molar ratio may be associated with cervical cancer.

Clinical manifestations of colorectal cancer patients from a large multicenter study in Colombia.

Colorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America.The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations.The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P = 0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3-T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P = 0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P = 0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P = 0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P = 0.005) and report a family history of cancer (17.4% vs 10.2%; P = 0.001).To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations.

[BabA2, oipA and cagE Helicobacter pylori genotypes in Colombian patients with gastroduodenal diseases]. / Frecuencia de los genotipos babA2, oipA y cagE de Helicobacter pylori en pacientes colombianos con enfermedades gastroduodenales.

INTRODUCTION: Helicobacter pylori infection is associated with the development of several gastroduodenal diseases. Bacterial virulence genes have been found associated with an increased risk for gastric disease. OBJECTIVES: Herein, associations were made between the presence of vacA, cagA, cagE, babA2 and oipA genes in H. pylori isolates and the range of clinical consequences of the infection. METHODS: PCR was used to amplify vacA, cagA, cagE, babA2 and oipA genes in 166 isolates-50 patients with peptic ulcer, 39 with non-atrophic gastritis, 26 with atrophic gastritis, 26 with intestinal metaplasia and 25 with gastric adenocarcinoma. RESULTS: cagA, cagE, babA2 and oipA genes were found in 73%, 75%, 48% and 74% of isolates, respectively. The cytotoxic vacA s1m1/cagA positive/cage positive genotype was present in 64% (100/157) of isolates. A higher frequency of cytotoxic strains was observed in cancer patients (84%), intestinal metaplasia (91%) and peptic ulcer (81%) in comparison with gastritis patients (50%) (p=0.002, 0.008, 0.007, respectively). The oipA and babA2 frequency was higher in cytotoxic isolates than in non-cytotoxic isolates (oipA: 81% vs. 52%, P=0,003; babA2: 58% vs. 12% (p<0.001). No significant association was found among clinical outcomes and oipA or babA2 genotypes, analyzed alone or in combination with vacA and cagA. CONCLUSION: Therefore, babA2 or oipA genes are not marker indicators of ulcer or cancer.

Draft Genome Sequence of a Helicobacter pylori Strain Isolated from a Patient with Diffuse Gastritis from a Region of High Cancer Risk in Colombia.

The draft genome sequence of one Colombian Helicobacter pylori strain is presented. This strain was isolated from a patient with diffuse gastritis from Tibaná, Boyacá, a region with high gastric cancer risk.

[Epstein-Barr virus presence in Colombian Hodgkin lymphoma cases and its relation to treatment response]. / Presencia del virus de Epstein-Barr en casos colombianos de linfoma de Hodgkin y su relación con la respuesta al tratamiento.

The role of Epstein-Barr virus as etiologic agent in Hodgkin lymphoma (HL) development has been supported by the detection of viral DNA in the Reed-Sternberg cell in a subset of HL, and the high levels of latent membrane protein 1 expression in these tumors. To gain further evidence of this relationship, lymph nodes from 67 patients with HL were analyzed for the presence of Epstein-Barr virus using EBERs in situ hybridization and LMP-1 immunohistochemistry. Virus presence was related to histological subtype, patients' treatment response and tumor infiltrating lymphocytes phenotype. EBERs transcripts were found in 67% of the cases and LMP-1 in the Reed-Sternberg tumor cells at a 56.7% rate. The prevalence, as determined by histological subtype, was 69.81% for nodular sclerosing, 85.71% for mixed cellularity and 40% for lymphocyte-rich. Epstein-Barr virus presence was more frequent in children (84.2%) in comparison with adults (60.4%). Positive patients presented higher failure-free survival rates than Epstein-Barr virus negative patients. CD4 positive infiltrating T cells were present in a higher proportion in relation to CD8 positive T infiltrating cells, the mean percentages for both subsets were higher in Epstein-Barr virus positive cases. A high percentage of Epstein-Barr virus was present in HL with a probable association with treatment response. This suggests an application of Epstein-Barr virus detection to use as a prognosis marker in treatment response for HL cases.

[Genotyping of Helicobacter pylori virulence factors vacA and cagA in individuals from two regions in Colombia with opposing risk for gastric cancer]. / Genotipificación de los factores de virulencia vacA y cagA de Helicobacter pylori en individuos de dos regiones de Colombia con riesgo opuesto de cáncer gástrico.

INTRODUCTION: The overall prevalence of Helicobacter pylori infection is high in Colombia; however, in the country´s Andean region, gastric cancer rates far surpass those in coastal areas. Helicobacter pylori genotypes cagA positive and vacA s1 and m1 are associated with an increased risk of gastric cancer. OBJECTIVE: To compare the distribution of H. pylori genotypes associated with virulence in two regions in Colombia with opposing risk for gastric cancer. MATERIALS AND METHODS: Four hundred and one gastric antral biopsies were obtained and analyzed from 401 individuals diagnosed with non-atrophic gastritis, atrophic gastritis and intestinal metaplasia: 256 came from the high-risk area cities of Tunja and Bogotá, and 145 from the low-risk area cities of Barranquilla, Santa Marta and Cartagena. Genotyping of virulence genes vacA and cagA was performed by PCR. RESULTS: No difference was observed in the frequency of H. pylori infection between the two areas (77.3% vs 77.9 %, p=non significant, ns). The presence of cagA was higher in the low-risk area (77.9% vs. 69.2 %, p=ns). The vacA s1 allele was also more prevalent in the low-risk area (61.8 % vs 72.0 %, p=ns). The vacA m1 allele was more prevalent in the high-risk area (57.2 % vs 42.8 %, p=ns). The cagA positive s1m1 combination was also more frequent in the low-risk area (48.9% vs 38.9%, p=ns). CONCLUSIONS: The differences in the risk of gastric cancer in these two geographic areas cannot be explained by differences in the prevalence of infection by H. pylori or by differences in the virulence of circulating strains.