Helicobacter pylori from Gastric Cancer and Duodenal Ulcer Show Same Phylogeographic Origin in the Andean Region in Colombia (original) (raw)
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The Helicobacter pylori genome evolution in different gastric cancer risk Colombian populations
Background The Helicobacter pylori (H. pylori) has evolved with its human host by nearly 110,000 years. Despite that H. pylori has been considered as a main factor for gastric cancer (GC) development, the pathogenesis depends on its hosts evolutive relations. Objective In this study we analyzed the H. pylori evolutive relations of two populations with different GC risk in Colombia. Materials and Methods We study 10 human genomes and same number of H. pylori genomes from Tuquerres: high GC risk population, and 9 genomes from Tumaco: low GC risk population. The evolutive analysis was performed using MLST, vacA virulence gene and alpA adhesine gene for H. pylori and human ancestry by phylogenomic analyzes. Results We found that the studied people from Tumaco had marked African and Amerindian ancestry and in minor proportion European ancestry. In contrast, the studied human population from Tuquerres had mainly Amerindian and European ancestry. The H. pylori phylogenomic trees from Tumac...
2013
Recently, H. pylori(HP) strains of European ancestral origin were seen to be associated with pre-malignant histological lesions in gastritis individuals from a high risk area for gastric cancer in Colombia. Our aim was to investigate the phylogeographic origin of HP strains from patients with HP-associated severe diseases as well as the genetic structure of the patients in order to determine whether they are predictors for duodenal ulcer or gastric carcinoma in the admixed population from South-east/Brazil. This study was approved by Institution Ethics Committee. Phylogeographic origin was evaluated in 103 HP strains from patients with gastric cancer (n=27), duodenal ulcer (n=28) and gastritis as the control group (n=48) by sequencing of both strands of 397 to 690 bp per gene of the atpA, efp, mutY, trpC, ureI , and yph housekeeping genes. The sequences were aligned (MUSCLE program), deposited in multi-locus sequence typing-MLST database (http:pubmlst.org.helicobacter). Neighbor joining tree of HP strains (1201 classified in ancestral haplogroups and our 103 strains) was created by MEGA5 using the Kimura model with 10,000 bootstraps. To determine the ethnicity of each patient, 106 validated SNPs were evaluated by Sequenon iPLEX Plataform at University of Minnesota-USA. We estimated individuals' ancestry using three parental groups: African and European from HapMap II/III and Brazilian rain forest Amerindians collected by our group, and accepted that these samples were representative of the parental population and that the patients were admixed individuals, by using the Structure 2.3.3. program. The data were analysed by Fisher, χ2, Student and correlation tests with SPSS 17. HP strains were classified as hpAfrica1 (66-64.1% hpWAfrica and 7-6.8% hpSAfrica) and hpEurope (30-29.1%). hpAfrica1 strains were observed in 85.7% of duodenal ulcer patients, in 88.9% of gastric cancer patients and in 52.1% of gastritis patients (p<0.001). However, when the patients were stratified by the bacterium virulence markers, the association disappeared (p>0.25), because 80.0% (24/30) of the hpEuropean strains were cagA-negative and s2i2m2 vacA genotype. s1i1m1 vacA genotype was associated with gastric cancer and s1i1m1or m2 with duodenal ulcer (p<0.001). The % of each ancestry (European, African and Amerindian) were similar in the 3 groups of patients (p>0.46) being the former the highest one (table). European ancestry was weakly positively correlated with corpus gastritis (r=0.2,p=0.05) and intestinal metaplasia (r=0.2,p=0.04) in the s1 vacA gastritis group. European ancestry also positively correlated with European origin of HP strains (r=0.5,p=0.01). We show that HP virulence markers more than HP ancestry "per se" and genetic structure of the population are the most important predictor for gastric cancer and duodenal ulcer in the studied admixed population.
Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk
Gut, 2011
Background and Aims-Helicobacter pylori colonises the stomach in half of all humans, and is the principal cause of gastric cancer, the second leading cause of cancer death worldwide. While gastric cancer rates correlate with H. pylori prevalence in some areas, there are regions where infection is nearly universal, but rates of gastric cancer are low. In the case of Colombia, there is a 25-fold increase in gastric cancer rate in the Andean mountain (high risk) region compared to the coastal (low risk) region, despite similarly high (~90%) H. pylori prevalence in the two locations. Our aim was to investigate the ancestral origin of H. pylori strains isolated from subjects in these high and low risk regions and to determine whether this is a predictive determinant of precancerous lesions.
Frontiers in Cellular and Infection Microbiology, 2017
Helicobacter pylori (HP) genetics may determine its clinical outcomes. Despite high prevalence of HP infection in Latin America (LA), there have been no phylogenetic studies in the region. We aimed to understand the structure of HP populations in LA mestizo individuals, where gastric cancer incidence remains high. The genome of 107 HP strains from Mexico, Nicaragua and Colombia were analyzed with 59 publicly available worldwide genomes. To study bacterial relationship on whole genome level we propose a virtual hybridization technique using thousands of high-entropy 13 bp DNA probes to generate fingerprints. Phylogenetic virtual genome fingerprint (VGF) was compared with Multi Locus Sequence Analysis (MLST) and with phylogenetic analyses of cagPAI virulence island sequences. With MLST some Nicaraguan and Mexican strains clustered close to Africa isolates, whereas European isolates were spread without clustering and intermingled with LA isolates. VGF analysis resulted in increased resolution of populations, separating European from LA strains. Furthermore, clusters with exclusively Colombian, Mexican, or Nicaraguan strains were observed, where the Colombian cluster separated from Europe, Asia, and Africa, while Nicaraguan and Mexican clades grouped close to Africa. In addition, a mixed large LA cluster including Mexican, Colombian, Nicaraguan, Peruvian, and Salvadorian strains was observed; all LA clusters separated from the Amerind clade. With cagPAI sequence analyses LA clades clearly separated from Europe, Asia and Amerind, and Colombian strains formed a single cluster. A NeighborNet analyses suggested frequent and recent recombination events particularly among LA strains. Results suggests that in the new world, H. pylori has evolved to fit mestizo LA populations, already 500 years after the Spanish colonization. This co-adaption may account for regional variability in gastric cancer risk.
Phylogenomics of Colombian Helicobacter pylori isolates
Gut pathogens, 2017
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. 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 Colomb...
Helicobacter, 2008
Background-cagA-positive and vacA s1 and m1 genotypes of Helicobacter pylori are associated with an elevated risk of gastric cancer (GC). We determined these genotypes using paraffinembedded gastric biopsy specimens harvested from infected individuals and compared genotype distributions in two Colombian populations residing in geographic regions with a high and low incidence of GC. Methods-DNA from paraffin-embedded gastric biopsies from 107 adults was amplified using primers specific for cagA, for the cag 'empty site', for the s and m alleles of vacA, and for H. pylori 16S rRNA. Results-H. pylori infection was detected by molecular assays in 97 (90.7%) biopsies. Complete genotyping of cagA and vacA was achieved in 94 (96.9%) cases. The presence of cagA was detected in 78 of 97 cases (80.4%); when considered separately, cagA and vacA s regions were not significantly associated with a particular geographic area. The vacA m1 allele and s1m1 genotypes were more common in the area of high risk for GC (p = .037 and p = .044, respectively), while the vacA m2 allele and s2m2 genotypes were more prevalent in the low-risk area. The prevalence of the combination of cagA-positive, vacA s1m1 genotypes was 84.3% and 60.5% for high and low risk areas, respectively (p = .011). Conclusions-H. pylori cagA and vacA genotyping from paraffin-embedded gastric biopsies permitted reliable typability and discrimination. The more virulent cagA-positive s1m1 strains, as well as vacA m1 genotype, were more prevalent in high risk than in low risk areas, which may contribute to the difference in GC risk between those two regions.
World Journal of Gastroenterology, 2017
Author contributions: All the authors that were involved in the acquisition and interpretation of the results, read and approved the final manuscript; Matta AJ, Pazos AJ and Bustamante-Rengifo JA conducted the microbiological and molecular tests; Matta AJ and Bravo LE analyzed the data; Matta AJ, Pazos AJ, Bustamante-Rengifo JA and Bravo LE wrote, edited, and revised the manuscript. Institutional review board statement: All procedures involving human participants were reviewed and approved by the Ethics Committee at
Scientific Reports, 2020
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...
Digestive diseases and sciences, 2002
Continuing attempts have been made to classify pathogenic strains within bacterial populations based on DNA fingerprints and to identify virulence factors in H. pylori. We studied 287 H. pylori isolates from patients with duodenal ulcer or gastric cancer from three different geographic regions. DNA fingerprints were generated using REP-PCR and analyzed by cluster analysis. The status of three candidate virulence factors-vacA polymorphism, cagA and iceA,-were examined by PCR amplification. Cluster analysis of the REP-PCR fingerprints showed clustering by geographic region but not by disease presentation. cagA was detected in 91.3% of the isolates. Differences in vacA subtypes were observed among the three geographic regions. There was no association between iceA subtypes and clinical outcome. We conclude that geographic differences among the H. pylori strains exist in single gene allelic variants as well as in the conserved noncoding regions such as REP sequences throughout the entir...