In the Shandong Intervention Trial, 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions, whereas 7.3 years of oral supplementation with garlic extract and oil (garlic treatment) or vitamin C, vitamin E, and selenium (vitamin treatment) did not. Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 randomly assigned subjects in this masked factorial placebo-controlled trial. Conditional logistic regression was used to estimate the odds of gastric cancer incidence, and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality. All statistical tests were two-sided. Gastric cancer was diagnosed in 3.0% of subjects who received H pylori treatment and in 4.6% of those who received placebo (odds ratio = 0.61, 95% confidence interval = 0.38 to 0.96, P = .032). Gastric cancer deaths occurred among 1.5% of subjects assigned H pylori treatment and among 2.1% of those assigned placebo (hazard ratio [HR] of death = 0.67, 95% CI = 0.36 to 1.28). Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality. Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer, a secondary endpoint (HR = 0.51, 95% CI = 0.30 to 0.87; P = .014).
This population-based intervention trial revealed that celecoxib treatment or H pylori eradication alone had beneficial effects on the regression of advanced gastric lesions. No favourable effects were seen for H pylori eradication followed by celecoxib treatment. Trial registration HARECCTR0500053 in accordance with WHO ICTRP requirements.
BackgroundTo investigate the potential of serum miRNAs as biomarkers for early detection of gastric cancer (GC), a population-based study was conducted in Linqu, a high-risk area of GC in China.Methodology/Principal FindingsAll subjects were selected from two large cohort studies. Differential miRNAs were identified in serum pools of GC and control using TaqMan low density array, and validated in individual from 82 pairs of GC and control, and 46 pairs of dysplasia and control by real-time quantitative reverse transcription-polymerase chain reaction. The temporal trends of identified serum miRNA expression were further explored in a retrospective study on 58 GC patients who had at least one pre-GC diagnosis serum sample based on the long-term follow-up population. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in GC patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for GC detection, and receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish GCs from controls with 82.4% sensitivity and 58.8% specificity. MiR-221 and miR-376c demonstrated significantly positive correlation with poor differentiation of GC, and miR-221 displayed higher level in dysplasia than in control. Furthermore, the retrospective study revealed an increasing trend of these three miRNA levels during GC development (P for trend<0.05), and this panel could classify serum samples collected up to 5 years ahead of clinical GC diagnosis with 79.3% overall accuracy.Conclusions/SignificanceThese data suggest that serum miR-221, miR-376c and miR-744 have strong potential as novel non-invasive biomarkers for early detection of GC.
Aberrant DNA methylation is associated with cancer development and progression. There are several types of specimens from which DNA methylation pattern can be measured and evaluated as an indicator of disease status (from normal biological process to pathologic condition) and even of pharmacologic response to therapy. Blood-based specimens such as cell-free circulating nucleic acid and DNA extracted from leukocytes in peripheral blood may be a potential source of noninvasive cancer biomarkers. In this article, we describe the characteristics of blood-based DNA methylation from different biological sources, detection methods, and the factors affecting DNA methylation. We provide a comprehensive literature review of blood-based DNA methylation as a cancer biomarker and focus on the study of DNA methylation using peripheral blood leukocytes. Although DNA methylation patterns measured in peripheral blood have great potential to be useful and informative biomarkers of cancer risk and prognosis, large systematic and unbiased prospective studies that consider biological plausibility and data analysis issues will be needed in order to develop a clinically feasible blood-based assay.
Among 2258 Helicobacter pylori-seropositive subjects randomly assigned to receive one-time H. pylori treatment with amoxicillin-omeprazole or its placebo, we evaluated the 15-year effect of treatment on gastric cancer incidence and mortality in subgroups defined by age, baseline gastric histopathology, and post-treatment infection status. We used conditional logistic and Cox regressions for covariable adjustments in incidence and mortality analyses, respectively. Treatment was associated with a statistically significant decrease in gastric cancer incidence (odds ratio = 0.36; 95% confidence interval [CI] = 0.17 to 0.79) and mortality (hazard ratio = 0.26; 95% CI = 0.09 to 0.79) at ages 55 years and older and a statistically significant decrease in incidence among those with intestinal metaplasia or dysplasia at baseline (odds ratio = 0.56; 95% CI = 0.34 to 0.91). Treatment benefits for incidence and mortality among those with and without post-treatment infection were similar. Thus H. pylori treatment can benefit older members and those with advanced baseline histopathology, and benefits are present even with post-treatment infection, suggesting treatment can benefit an entire population, not just the young or those with mild histopathology.
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