Faculty Bibliography

GOAL: To study the rate at which Helicobacter pylori infection is treated in an immigrant cohort after diagnosis by esophagogastroduodenoscopy (EGD). BACKGROUND: Gastric cancer is the second leading cause of cancer death worldwide, and is especially prevalent in East Asia; immigrants from this part of the world remain at higher risk. Infection with H. pylori is a known risk factor for gastric cancer. There have been no studies of completion of H. pylori treatment in immigrant populations. STUDY: Prospective cohort study of East Asian immigrants diagnosed with H. pylori infection who underwent EGD in a gastric cancer screening protocol. Our primary outcome was self-report or chart evidence of completion of treatment of H. pylori. RESULTS: Sixty-eight of the 126 participants (54%) tested positive for H. pylori infection on EGD. Forty-nine (72%) were seen for a follow-up visit at one of the clinics involved in the study. According to clinic records, 39 of these 49 participants (57% of all H. pylori-positive participants) were prescribed treatment. Only 31 participants (46%) completed treatment. Of possible explanatory factors, only having a 'regular doctor' was significantly associated with treatment completion (odds ratio=5.6; 95% confidence interval, 1.2-25.0). CONCLUSIONS: In a sample of Asian immigrants, the rate of treatment of H. pylori infection, a potentially modifiable risk factor, was lower than expected. Having a 'regular doctor' appeared to increase the likelihood of receiving appropriate follow-up care

The microbiota of the human stomach and the influence of Helicobacter pylori colonization on its composition remain largely unknown. We characterized bacterial diversity within the human gastric mucosa by using a small subunit 16S rDNA clone library approach and analyzed 1,833 sequences generated by broad-range bacterial PCR from 23 gastric endoscopic biopsy samples. A diverse community of 128 phylotypes was identified, featuring diversity at this site greater than previously described. The majority of sequences were assigned to the Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria phyla. Ten percent of the phylotypes were previously uncharacterized, including a Deinococcus-related organism, relatives of which have been found in extreme environments but not reported before in humans. The gastric clone libraries from 19 subjects contained H. pylori rDNA; however, only 12 of these subjects tested positive for H. pylori by conventional laboratory methods. Statistical analysis revealed a large degree of intersubject variability of the gastric ecosystem. The presence of H. pylori did not affect the composition of the gastric community. This gastric bacterial rDNA data set was significantly different from sequence collections of the human mouth and esophagus described in other studies, indicating that the human stomach may be home to a distinct microbial eco-system. The gastric microbiota may play important, as-yet-undiscovered roles in human health and disease

Gastric cancer is the second most common cancer associated death cause worldwide. Several factors have been associated with higher risk to develop gastric cancer, among them genetic predisposition. The p53 gene has a polymorphism located at codon 72. which has been associated with higher risk of several types of cancer, including gastric cancer. The aim of this study was to determine the association of p53, codon 72 polymorphism. with the risk of gastric cancer and pre-malignant lesions in a high-risk population from Costa Rica. The genotyping was carried out by PCR-RFLP in 58 gastric cancer patients, 99 controls and 41 individuals classified as group I or II. according to the Japanese histological classification. No association was found for p53. codon 72 polymorphism with neither the risk of gastric cancer nor the risk of less severe gastric lesions in the studied population. Based on this study and taking into account other studies carried out with p53, codon 72 polymorphism. the role of this polymorphismn in the development of gastric cancer remains unclear. De novo mutations on p53 gene produced during neoplasic development of this disease might play a greater role than germinal polymorphisms of the gene. Other polymorphic genes have been associated with higher risk to develop gastric cancer.

Helicobacter pylori prevalence is higher in developing countries than in industrialized countries, and within the latter, higher among immigrants than among nativeborn residents. Using a point-prevalence survey, we sought to identify risk factors for H. pylori seropositivity in US urban East Asian-born populations. At a clinic in New York City, we consecutively enrolled 194 East Asian-born adults, who then responded to a survey and provided a blood sample. Assays were performed to detect IgG antibodies against whole cell (WC) and cytotoxin associated gene A (CagA) antigens of H. pylori. For this group (mean age 50.2+/-14.7 years), the mean period of residence in the United States was 11.9+/-7.7 years. The total H. pylori seroprevalence was 70.1%, with highest (81.4%) in Fujianese immigrants. Multiple logistic regression analysis indicated an independent association of H. pylori seropositivity with Fujianese origin [odds ratios (OR) =2.3, 95% confidence interval (95% CI) =1.05-5.0] and inverse associations with period in the United States (OR per year of residency in the United States =0.95, 95% CI =0.91-0.99) and with a history of dyspepsia (OR for a history of stomach pain =0.52, 95% CI =0.3-1.0). We conclude that H. pylori is highly prevalent among recent East Asian immigrants, especially among Fujianese. The protective effects of history of dyspepsia and duration in the United States suggest that these may be markers for antibiotic therapies.

Multiple Helicobacter pylori strains may colonize an individual host. Using enzyme-linked immunosorbent assay and line probe assay (LiPA) techniques, we analyzed the prevalence of mixed H. pylori colonization in 127 subjects from Venezuela, a country of high H. pylori prevalence, from three regions representing different population groups: the Andes (Merida), where Caucasian mestizos predominate, a major city near the coast (Caracas), where Amerindian-Caucasian-African mestizos predominate, and an Amazonian community (Puerto Ayacucho), where Amerindians predominate and mestizos reflect Amerindian and Caucasian ancestry. Among 121 H. pylori-positive persons, the prevalence of cagA-positive strains varied from 50% (Merida) to 86% (Puerto Ayacucho) by LiPA. Rates of mixed colonization also varied, as assessed by LiPA of the vacA s (mean, 49%) and m (mean, 26%) regions. In total, 55% of the individuals had genotypic evidence of mixed colonization. vacA s1c, a marker of Amerindian (East Asian) origin, was present in all three populations, especially from Puerto Ayacucho (86%). These results demonstrate the high prevalence of mixed colonization and indicate that the H. pylori East Asian vacA genotype has survived in all three populations tested

We assessed the sensitivity and specificity of H. pylori IgG and IgA with a commercial immunoassay performed in Chile and a second non-commercial immunoassay performed in a reference laboratory in the United States, in serum of 80 children and adults referred for gastrointestinal endoscopies in a developing country. Overall, 56% of the patients were infected with H. pylori based on rapid urease test and staining techniques on gastric biopsies. When Receiver Operator Curves (ROC) were developed, the sensitivity and specificity were similar for IgG and IgA. Both immunoassays exhibited better specificity, positive and negative predictive value (NPV) in children than in adults when cut-off values were corrected according to the local population than when they were assessed using the cut-off values pre-defined in other populations. These results underline the need to establish more precise cut-off values corrected in the local populations where assessments of antibodies as diagnostic markers of H. pylori infection are planning

Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1beta (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/- had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34-10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09-7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed

BACKGROUND: The objective was to investigate the association of Helicobacter pylori and serum pepsinogen (PG) levels with gastric adenocarcinoma. METHODS: Serum obtained from 299 patients at the time of cancer diagnosis and from 336 population-based control subjects was tested for PG I, PG II, and antibodies to H. pylori and to CagA. RESULTS: Subjects with low PG I levels or low PG I/II ratios were at increased risk for cardia and noncardia gastric cancer, whereas those with H. pylori or CagA seropositivity had an elevated risk for noncardia cancer only. Subjects seropositive for either H. pylori or CagA who had low PG I levels had the highest odds ratio (OR) (9.21 [95% confidence interval {CI}, 4.95-17.13]) for noncardia cancer, compared with subjects with neither factor. Elevated risks were also found among subjects with only 1 factor (OR, 5.40 [95% CI, 2.61-11.20] for low PG I level only; OR, 4.86 [95% CI, 5.90-8.13] for H. pylori or CagA seropositivity only). This pattern persisted when PG I/II ratio replaced PG I level and when CagA seropositivity alone replaced H. pylori immunoglobulin G or CagA seropositivity. CONCLUSIONS: The results suggest that persons with both H. pylori or CagA seropositivity and a low PG I level or PG I/II ratio are highly susceptible to development of noncardia gastric cancer