Introduction: Population-based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40–64-year-old individuals. The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome. Methods and analysis: Individuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoes H pylori testing and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase. Ethics and dissemination: The study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number: NCT02047994

Background : Detection of diseases via exhaled breath remains an attractive idea despite persisting gaps in understanding the origin of volatile organic compounds (VOCs) and their relationship with the disease of interest. Data on factors potentially influencing the results of breath analysis remain rather sparse and often controversial. In this study, we aimed to investigate the associations of common VOCs in exhaled breath of average-risk individuals with socio-demographic and lifestyle factors, medical conditions as well as diet. Methods : Alveolar breath samples of 1447 men and women were collected in the morning after fasting and were analyzed using gas-chromatography linked with mass-spectrometry. Study participants were 40–64 years old, cancer-free, with overall good health status. The associations between selected VOCs and various factors determined from the questionnaire data were assessed using two-part-Wilcoxon test and Jonckheere–Terpstra trend test. Results : Fifteen VOCs where each of them was detected in at least 80% of the study population were included in this analysis. Statistically significant associations with various VOCs were demonstrated for gender and consumption of certain foods, such as coffee, leeks and garlic, while smoking was not associated with any of the analyzed compounds. Conclusion : Factors potentially modifying the composition of exhaled breath, such as dietary factors, deserve careful attention in the design and analysis of studies accessing the use of VOCs as diagnostic markers.

It has been shown that the gut microbiota plays a central role in human health and disease. A wide range of volatile metabolites present in exhaled breath have been linked with gut microbiota and proposed as a non-invasive marker for monitoring pathological conditions. The aim of this study was to examine the possible correlation between volatile organic compounds (VOCs) in exhaled breath and the fecal microbiome by multivariate statistical analysis in gastric cancer patients (n = 16) and healthy controls (n = 33). Shotgun metagenomic sequencing was used to characterize the fecal microbiota. Breath-VOC profiles in the same participants were identified by an untargeted gas chromatography–mass spectrometry (GC–MS) technique. A multivariate statistical approach involving a canonical correlation analysis (CCA) and sparse principal component analysis identified the significant relationship between the breath VOCs and fecal microbiota. This relation was found to differ between gastric cancer patients and healthy controls. In 16 cancer cases, 14 distinct metabolites identified from the breath belonging to hydrocarbons, alcohols, aromatics, ketones, ethers, and organosulfur compounds were highly correlated with 33 fecal bacterial taxa (correlation of 0.891, p-value 0.045), whereas in 33 healthy controls, 7 volatile metabolites belonging to alcohols, aldehydes, esters, phenols, and benzamide derivatives correlated with 17 bacterial taxa (correlation of 0.871, p-value 0.0007). This study suggested that the correlation between fecal microbiota and breath VOCs was effective in identifying exhaled volatile metabolites and the functional effects of microbiome, thus helping to understand cancer-related changes and improving the survival and life expectancy in gastric cancer patients.

Background and Aims: The prevalence of Helicobacter pylori (H. pylori) infection is higher in developing countries and is often linked to lower socioeconomic status. Few studies have investigated the association between H. pylori and individual level characteristics in Europe, where several countries have a high prevalence of H. pylori infection. The study aimed to identify risk factors for H. pylori infection among adults in a large clinical trial in Latvia. Methods: 1,855 participants (40-64 years) of the “Multicenter randomized study of H. pylori eradication and pepsinogen testing for prevention of gastric cancer mortality” (GISTAR study) in Latvia tested for H. pylori IgG antibodies were included in a cross-sectional analysis. Sociodemographic, lifestyle and medical factors were compared for participants seropositive (H. pylori+) and seronegative. Mutually adjusted odds ratios (OR) were calculated for H. pylori+ and factors significant in univariate analysis (education, smoking, binge drinking, several dietary habits, history of H. pylori eradication and disease), adjusting for age, gender and income. Results: Of the participants 1,044 (55.4%) were H. pylori seropositive. The infection was associated with current (OR: 1.34, 95%CI: 1.01-1.78) and former (OR: 1.38; 95%CI: 1.03-1.85) smoking, binge drinking (OR: 1.35; 95%CI: 1.03-1.78), having ≥200g dairy daily (OR: 1.37; 95%CI: 1.11-1.69), and very hot food/drinks (OR: 1.32; 95%CI: 1.03-1.69) and inversely with ≥400g vegetables/fruit daily (OR: 0.76; 95%CI: 0.60-0.96), history of H. pylori eradication (OR: 0.57; 95%CI: 0.39-0.84), peptic ulcer (OR: 0.55; 95%CI: 0.38-0.80) and cardiovascular disease (OR: 0.78; 95%CI: 0.61-0.99). Conclusions: After mutual adjustment, H. pylori seropositivity was associated with lifestyle and in particular dietary factors rather than socioeconomic indicators in contrast to the majority of other studies.