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.

Estrogens may influence gastric cancer risk, but published studies are inconclusive. We therefore carried out a meta-analysis addressing the associations of gastric cancer in women with menstrual and reproductive factors and with use of estrogen- and antiestrogen-related therapies. Searches of PubMed up to June, 2011 and review of citations yielded a total of 28 independent studies, including at least one exposure of interest. Random effects pooled estimates of relative risk (RR) and corresponding 95% CIs were calculated for eight exposures reported in at least five studies, including: age at menarche, age at menopause, years of fertility, parity, age at first birth, oral contraceptive use, hormone replacement therapy (HRT), and tamoxifen treatment. Longer years of fertility (RR = 0.74, 95% CI: 0.63–0.86) and HRT (RR = 0.77; 95% CI: 0.64–0.92) were each associated with decreased gastric cancer risk. Conversely, tamoxifen treatment was associated with increased risk (RR = 1.82; 95% CI: 1.39–2.38). The other five exposures were not significantly associated. Our analysis supports the hypothesis that longer exposure to estrogen effects of either ovarian or exogenous origin may decrease risk of gastric cancer. Additional studies are warranted to extend this finding and to identify the underlying mechanisms. Cancer Epidemiol Biomarkers Prev; 21(1); 20–38. ©2011 AACR.

The initial step for noncardia gastric carcinogenesis is atrophic gastritis, driven by either Helicobacter pylori infection or autoimmunity. In recent decades, the prevalence rates of these two major causes declined and increased, respectively, with changes in Western lifestyles. We therefore assessed gastric cancer incidence trends for US race/ethnic groups, 1995–2013. Age-standardized rates (ASRs) from 45 North American Association of Central Cancer Tumor Registries were summarized by estimated annual percentage change (EAPC) and 95% confidence intervals (CIs). Age period cohort models supplemented standard descriptive techniques and projected future trends. There were 137 447 noncardia cancers in 4.4 billion person-years of observation. Among non-Hispanic whites, the ASR was 2.2 per 100 000 person-years, with an EAPC of –2.3% (95% CI = –2.0% to –2.6%). Notwithstanding this overall decline, EAPCs rose 1.3% (95% CI = 0.6% to 2.1%) for persons younger than age 50 years and fell –2.6% (95% CI = –2.4% to –2.9%) for older individuals. These converging trends manifested a birth cohort effect more pronounced among women than men, with incidence among women born in 1983 twofold (95% CI = 1.1-fold to 3.6-fold) greater than those born in 1951. Age interaction was also statistically significant among Hispanic whites, with slightly increasing vs decreasing EAPCs for younger and older individuals, respectively. Incidence declined regardless of age for other races. Current trends foreshadow expected reversals in both falling incidence and male predominance among non-Hispanic whites. Dysbiosis of the gastric microbiome associated with modern living conditions may be increasing risk of autoimmune gastritis and consequent noncardia cancer. The changing face by age and sex of gastric cancer warrants analytical studies to identify potential causal mechanisms.

Ized published literature and calculated region- and country-specific prevalences of antibiotic resistance. METHODS: Searches of PubMed and regional databases for observational studies evaluatingH. pyloriantibiotic resistance yielded a total of 59 independent studies (56 in adults, 2 in children, and 1 in both groups) published up to October 2013 regardingH. pyloriisolates 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 priorH. pylori-eradication therapy. RESULTS: 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. CONCLUSIONS: Resistance to first-line anti-H. pyloriantibiotics 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....

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Background and aim Age-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. Methods Gastric 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. Results Based 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. Conclusions Long- 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.