Faculty Bibliography

Gastric colonization by Helicobacter pylori is a risk factor for noncardia gastric cancer. The association between H. pylori and cancer may be attributable to increased epithelial cell turnover, possibly related to antigastric antibodies. Two previous studies reported a disproportionate increase in proliferation relative to apoptosis in patients with H. pylori strains expressing the virulence-related cagA gene. This has led to the hypothesis that an abrogation of apoptosis by cagA-positive strains may promote neoplasia. We, therefore, examined the effect of H. pylori on gastric epithelial proliferation, apoptosis, and the presence of serum antiparietal cell antibodies in a large prospective study. Proliferation and apoptosis were evaluated 'blindly' using validated immunohistochemical methods in two antral and two gastric corpus biopsies from 60 patients with nonulcer dyspepsia, and results were correlated with the presence of serum antiparietal cell antibodies. H. pylori colonization was assessed by histology, biopsy urease test, and serology. Proliferation was increased 2-fold in both antrum and corpus in H. pylori-positive patients, was not related to H. pylori cagA status, and was positively correlated with histological gastritis. Apoptosis was increased in the antrum and body only in patients with cagA-positive H. pylori strains. Antiparietal cell antibodies were not more prevalent in H. pylori colonization, and their presence was inversely related to epithelial apoptosis scores we therefore conclude that in patients with nonulcer dyspepsia, H. pylori carriage is associated with increased proliferation. Futhermore the cag pathogenicity island is associated with increased apoptosis. Our results do not support the hypothesis that there is a relative deficiency of gastric epithelial cell apoptosis associated with the carriage of cagA-positive strains. Host factors may be more important than bacterial products in determining the long-term outcome of H. pylori colonization

BACKGROUND: Studies in adult populations in selected countries with widely varying rates of gastric cancer have shown a weak correlation between gastric cancer mortality rates and the prevalence of CagA+ strains of H. pylori. However, only limited data are available in ethnically homogenous populations with varying rates in the same region. METHODS; We compared the prevalence of H. pylori in general and of CagA+ strains in particular among children in Shandong Province, China in areas at high (Linqu County) and low risk (Cangshan County) of gastric cancer. H. pylori status among children aged 3 to 12 years was determined by 13C-UBT, and CagA status was determined by enzyme-linked immunosorbent assay (ELISA). Because of the difficulty in obtaining blood from young children aged 3 to 4 years and from some children aged 5 years, CagA status was determined among part of children 5 years old and children 6 to 12 years old. RESULTS; Among 98 children aged 3 to 12 years in Linqu, 68 (69.4%) was H. pylori-positive, as compared with 29 (28.7%) among 101 children in Cangshan. Among children positive for 13C-UBT, the proportion of the CagA+ strains were identified was 46 (88.5%) of 52 in Linqu and 13 (81.3%) of 16 in Cangshan, respectively. CONCLUSIONS: The prevalence of H. pylori was nearly three times higher among children in Linqu than in Cangshan, which may contribute to the large differential in gastric cancer rates for two neighboring populations in Shandong Province

There are no reports, to our knowledge, on the expression of Lewis (Le) antigens in Helicobacter pylori isolates from children. The aim of this study was to compare the expression of Le antigens by H. pylori isolates from children and from adults. Totals of 278 clones from 22 children with recurrent abdominal pain and 293 clones from 22 adults with (n=10) or without (n=12) duodenal ulcer were studied. Expression of Le(x) and Le(y) antigens was determined by ELISA, using monoclonal anti-Le antibodies. The Le phenotype of the patients was determined in gastric juice with a hemagglutination assay. Clones expressing Le(x) were more common in children than in adults (55.4% vs. 33.4%, respectively; P<.001), and Le(y) was more common in adults than in children (81.6% vs. 66%, respectively; P<.01). A trend analysis showed a significant decline in frequency of clones expressing Le(x) with age (P=.021). In this community, expression of Le antigens differs in H. pylori isolates obtained from children versus adults

BACKGROUND: Helicobacter pylori carriage (i.e., persistent exposure to the organism without gastric epithelial cell invasion) is an established risk factor for noncardia gastric cancer. However, its association with the risk of cancer of the gastric cardia is controversial. Consequently, we designed this prospective, nested case-control study to further explore the subsite-specific gastric cancer risks associated with H. pylori seropositivity (a surrogate marker for persistent exposure). METHODS: A total of 99 patients with gastric cardia cancer, 82 patients with noncardia gastric cancer, and 192 cancer-free subjects were selected from among the participants (n = 29 584) of a nutrition intervention trial previously conducted in Linxian, China. H. pylori seropositivity was determined by assaying for the presence of H. pylori whole cell and CagA antibodies in baseline serum samples from all subjects. Seropositivity was defined as one or both serum assays being positive. Odds ratios (ORs) for subsite-specific gastric cancer were estimated by multivariate logistic regression analyses. All statistical comparisons were two-sided (alpha =.05). RESULTS: H. pylori seropositivity rates for subjects with gastric cardia cancer, noncardia gastric cancer, and gastric cardia and noncardia cancers combined were 70% (P =.02), 72% (P: =.01), and 71% (P =.003) compared with 56% for cancer-free control subjects. OR estimates for H. pylori seropositivity were 1.87 (95% confidence interval [CI] = 1.10 to 3.17) for gastric cardia cancer, 2.29 (95% CI = 1.26 to 4.14) for noncardia gastric cancer, and 2.04 (95% CI = 1.31 to 3.18) for gastric cardia and noncardia cancers combined. CONCLUSIONS: H. pylori seropositivity was associated with increased risks for both gastric cardia cancer and noncardia gastric cancer in this well-characterized cohort. Thus, H. pylori carriage may increase the risk of cancer throughout the stomach

The efficacy of the string culture test to isolate Helicobacter pylori from gastric secretions of 28 volunteers was studied. With the urea breath test (UBT) as the 'gold standard,' the string culture test showed a sensitivity of 75% and a specificity of 100%. The results of string culture did not correlate with the UBT results, with serum antibody levels, or with the pH levels of gastric secretions

BACKGROUND: Pancreatic cancer is among the most fatal cancers worldwide and one for which few preventable risk factors have been established. Gastric carriage of Helicobacter pylori, particularly cytotoxin-associated gene-A-positive (CagA+) strains, is known to be a risk factor for peptic ulcer disease and gastric cancer and may have a similar etiologic relationship with pancreatic cancer. METHODS: We investigated the association of H. pylori carriage and exocrine pancreatic cancer in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29 133 male Finnish smokers aged 50-69 years at baseline. Case subjects (n = 121) were matched on date of baseline serum collection, study center, age, trial intervention, and completion of the dietary questionnaire to 226 control subjects who were alive at the time the matching case subject was diagnosed and who remained free of cancer, during up to 10 years of follow-up. Levels of immunoglobulin G antibodies to H. pylori whole-cell and CagA+ antigens from stored baseline serum were measured by enzyme-linked immunosorbent assay. Smoking-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression. Statistical tests were two-sided. RESULTS: Seroprevalence of H. pylori was 82% and 73% among case and control subjects, respectively. Compared with seronegative subjects, those with H. pylori or CagA+ strains were at statistically significantly elevated risk of pancreatic cancer (OR = 1.87 [95% CI = 1.05 to 3.34]; OR = 2.01 [95% CI = 1.09 to 3.70], respectively). CONCLUSIONS: Our findings support a possible role for H. pylori carriage in the development of exocrine pancreatic cancer