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ObjectivesThe incidence of gastric cancer continues to decrease globally, approaching levels that in some populations could define it as a rare disease. To explore this on a wider scale, we predict its future burden in 34 countries with long-standing population-based data.MethodsData on gastric cancer incidence by year of diagnosis, sex and age were extracted for 92 cancer registries in 34 countries included in Cancer Incidence in Five Continents Plus. Numbers of new cases and age-standardised incidence rates (ASR per 100 000) were predicted up to 2035 by fitting and extrapolating age–period–cohort models.ResultsOverall gastric cancer incidence rates are predicted to continue falling in the future in the majority of countries, including high-incidence countries such as Japan (ASR 36 in 2010 vs ASR 30 in 2035) but also low-incidence countries such as Australia (ASR 5.1 in 2010 vs ASR 4.6 in 2035). A total of 16 countries are predicted to fall below the rare disease threshold (defined as 6 per 100 000 person-years) by 2035, while the number of newly diagnosed cases remains high and is predicted to continue growing. In contrast, incidence increases were seen in younger age groups (below age 50 years) in both low-incidence and high-incidence populations.ConclusionsWhile gastric cancer is predicted to become a rare disease in a growing number of countries, incidence levels remain high in some regions, and increasing risks have been observed in younger generations. The predicted growing number of new cases highlights that gastric cancer remains a major challenge to public health on a global scale.

Latin America has a high prevalence of Helicobacter pylori infection and associated diseases, including gastric cancer. Antibiotic therapy can eradicate the bacterial infection and decrease associated morbidity and mortality. To tailor recommendations for optimal treatments, we summarized published literature and calculated region- and country-specific prevalences of antibiotic resistance. Searches of PubMed and regional databases for observational studies evaluating H. pylori antibiotic resistance yielded a total of 59 independent studies (56 in adults, 2 in children, and 1 in both groups) published up to October 2013 regarding H. pylori isolates collected between 1988 and 2011. Study-specific prevalences of primary resistance to commonly prescribed antibiotics were summarized using random-effects models. Between-study heterogeneity was assessed by meta-regression. As a sensitivity analysis, we extended our research to studies of patients with prior H. pylori-eradication therapy. Summary prevalences of antimicrobial primary resistance among adults varied by antibiotic, including 12% for clarithromycin (n=35 studies), 53% for metronidazole (n=34), 4% for amoxicillin (n=28), 6% for tetracycline (n=20), 3% for furazolidone (n=6), 15% for fluoroquinolones (n=5), and 8% for dual clarithromycin and metronidazole (n=10). Resistance prevalence varied significantly by country, but not by year of sample collection. Analyses including studies of patients with prior therapy yielded similar estimates. Pediatric reports were too few to be summarized by meta-analysis. Resistance to first-line anti-H. pylori antibiotics is high in Latin American populations. In some countries, the empirical use of clarithromycin without susceptibility testing may not be appropriate. These findings stress the need for appropriate surveillance programs, improved antimicrobial regulations, and increased public awareness.

ObjectiveTo evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions.Design795 adults with precancerous gastric lesions were randomised to receive anti-H. pylori treatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time of H. pylori exposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1–6). The score difference between baseline and 16 years was modelled by generalised linear models.ResultsIndividuals who were continuously infected with H. pylori for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected with H. pylori. The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001).ConclusionsLong-term exposure to H. pylori infection was associated with progression of precancerous lesions. Individuals infected with H. pylori with these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.

Background: Latin America has among the highest gastric cancer incidence rates in the world, for reasons that are still unknown. In order to identify region-specific risk factors for gastric cancer, we conducted a meta-analysis summarizing published literature. Methods: Searches of PubMed and regional databases for relevant studies published up to December 2011 yielded a total of 29 independent case–control studies. We calculated summary odds ratios (OR) for risk factors reported in at least five studies, including socioeconomic status (education), lifestyle habits (smoking and alcohol use), dietary factors (consumption of fruits, total vegetables, green vegetables, chili pepper, total meat, processed meat, red meat, fish, and salt), and host genetic variants (IL1B-511T, IL1B-31C, IL1RN*2, TNFA-308A, TP53 codon 72 Arg, and GSTM1 null). Study-specific ORs were extracted and summarized using random-effects models. Results: Chili pepper was the only region-specific factor reported in at least five studies. Consistent with multifactorial pathogenesis, smoking, alcohol use, high consumption of red meat or processed meat, excessive salt intake, and carriage of IL1RN*2 were each associated with a moderate increase in gastric cancer risk. Conversely, higher levels of education, fruit consumption, and total vegetable consumption were each associated with a moderately decreased risk. The other exposures were not significantly associated. No prospective study data were identified. Conclusion: Risk factor associations for gastric cancer in Latin America are based on case–control comparisons that have uncertain reliability, particularly with regard to diet; the specific factors identified and their magnitudes of association are largely similar to those globally recognized. Future studies should emphasize prospective data collection and focus on region-specific exposures that may explain high gastric cancer risk.

Background and objective About 9% of gastric carcinomas have Epstein–Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors. Methods We combined individual-level data on 4599 gastric cancer patients diagnosed between 1976 and 2010 from 13 studies in Asia (n=8), Europe (n=3), and Latin America (n=2). EBV positivity of tumours was assessed by in situ hybridisation. Mortality HRs for EBV positivity were estimated by Cox regression models stratified by study, adjusted for distributions of sex (71% male), age (mean 58 years), stage (52% tumour-node-metastasis stages III or IV), tumour histology (49% poorly differentiated, 57% Lauren intestinal-type), anatomic subsite (70% non-cardia) and year of diagnosis. Variations by study and continent were assessed using study-specific HRs for EBV positivity. Results During median 3.0 years follow-up, 49% of patients died. Stage was strongly predictive of mortality, with unadjusted HRs (vs stage I) of 3.1 for stage II, 8.1 for stage III and 13.2 for stage IV. Tumour EBV positivity was 8.2% overall and inversely associated with stage (adjusted OR: 0.79 per unit change). Adjusted for stage and other confounders, EBV positivity was associated with lower mortality (HR, 0.72; 95% CI 0.61 to 0.86), with low heterogeneity among the study populations (p=0.2). The association did not significantly vary across patient or tumour characteristics. There was no significant variation among the three continent-specific HRs (p=0.4). Conclusions Our findings suggest that tumour EBV positivity is an additional prognostic indicator in gastric cancer. Further studies are warranted to identify the mechanisms underlying this protective association.

Pernicious anemia (PA) is a risk factor for gastric cancer. Other autoimmune conditions may also contribute. In a case-control study, we evaluated 47 autoimmune conditions among 39,125 gastric cancers and 200,000 cancer-free controls. Six conditions were associated with increased gastric cancer risk (range of adjusted odds ratios: 1.28-1.93, P < 0.05): PA, membranous nephropathy, primary biliary cirrhosis, pure red cell aplasia, primary sclerosing cholangitis, and Graves disease. PA was associated with 8 other autoimmune conditions (adjusted odds ratios: 1.57-4.54, P < 0.05). Autoimmune conditions associated with gastric cancer or PA may reflect effects of autoimmune gastritis or other carcinogenic pathways.

Tissue-based functional genomics resources including molecular quantitative trait loci datasets lack diversity in ancestry and tissue types and thus are inadequate for comprehensively investigating gene regulation. Global efforts to increase the tissue diversity will help achieve more equitable medical care.

BackgroundFamily history may inform risks of gastric cancer and preneoplastic lesions.MethodsWe examined associations with history of cancer in first-degree relatives for 307 incident gastric cancer cases among 20,720 male smokers in a prospective study in Finland. Cox regression was used to calculate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI). Logistic regression was used to estimate odds ratios (OR) and 95% CIs for low serum pepsinogen, a marker of gastric atrophy.ResultsGastric cancer risk was associated with gastric cancer history in first-degree relatives overall (HR 1.56, 95% CI 1.15–2.12), in fathers (HR 1.67, 95% CI 1.09–2.55) and in siblings (HR 2.05, 95% CI 1.25–3.38). Associations were significant for noncardia (HR 1.83, 95% CI 1.30–2.57) but not cardia (HR 0.93, 95% CI 0.46–1.87) cancers, and marginal for both intestinal—(HR 1.53, 95% CI 0.92–2.55) and diffuse-type (HR 1.47, 95% CI 0.72–3.03) histologies. Family history of other cancer types was not associated with gastric cancer risk. Family history of gastric cancer was associated with low pepsinogen (OR 1.29, 95% CI 1.11–1.50).ConclusionsFamily history of gastric cancer is strongly associated with specific subtypes of gastric cancer as well as with gastric atrophy, a risk factor for developing this malignancy.

Blood group antigens are inherited traits that may play a role in immune and inflammatory processes. We investigated associations between blood groups and circulating inflammation-related molecules in 3537 non-Hispanic white participants selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Whole-genome scans were used to infer blood types for 12 common antigen systems based on well-characterized single-nucleotide polymorphisms. Serum levels of 96 biomarkers were measured on multiplex fluorescent bead-based panels. We estimated marker associations with blood type using weighted linear or logistic regression models adjusted for age, sex, smoking status, and principal components of population substructure. Bonferroni correction was used to control for multiple comparisons, with two-sided p values < 0.05 considered statistically significant. Among the 1152 associations tested, 10 were statistically significant. Duffy blood type was associated with levels of CXCL6/GCP2, CXCL5/ENA78, CCL11/EOTAXIN, CXCL1/GRO, CCL2/MCP1, CCL13/MCP4, and CCL17/TARC, whereas ABO blood type was associated with levels of sVEGFR2, sVEGFR3, and sGP130. Post hoc pairwise t-tests showed that individuals with type Fy(a+b−) had the lowest mean levels of all Duffy-associated markers, while individuals with type A blood had the lowest mean levels of all ABO-associated markers. Additional work is warranted to explore potential clinical implications of these differences.

Background and aimAge-specific analyses of non-cardia gastric cancer incidence reveal divergent trends among US whites: rates are declining in individuals aged 40 years and older but rising in younger persons. To investigate this heterogeneity further, incidence trends were evaluated by anatomical subsite.MethodsGastric cancer incidence data for 1976–2007 were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and the US Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR). Incidence rates and estimated annual percentage change were calculated by age group (25–39, 40–59 and 60–84 years), race/ethnicity and subsite.ResultsBased on data from the nine oldest SEER registries (covering ∼10% of the US population), rates for all non-cardia subsites decreased in whites and blacks, except for corpus cancer, which increased between 1976 and 2007 with estimated annual percentage changes of 1.0% (95% CI 0.1% to 1.9%) for whites and 3.5% (95% CI 1.8% to 5.2%) for blacks. In contrast, rates for all non-cardia subsites including corpus cancer declined among other races. In combined data from NPCR and SEER registries (covering 89% of the US population), corpus cancer significantly increased between 1999 and 2007 among younger and middle-aged whites; in ethnic-specific analyses, rates significantly increased among the same age groups in non-Hispanic whites and were stable among Hispanic whites. Age-specific rates for all subsites declined or were stable in this period among blacks and other races.ConclusionsLong- and short-term incidence trends for gastric cancers indicate a shifting distribution by anatomical subsite. Corpus cancer may have distinctive aetiology and changing risk factor exposures, warranting further investigation.