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We evaluated associations between Epstein-Barr virus (EBV) antibody levels and precancerous gastric lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia) in 183 subjects from Linqu, China. Immunoglobulin G antibody titers to EBV nuclear antigen (EBNA) and viral capsid antigen (VCA) were determined by two-fold serial dilution using immunofluorescence assays. Histological progression and regression were assessed by gastroscopic examination at the time of phlebotomy and at follow up 2 years later. Antibody titers did not differ significantly among histological diagnoses determined at the time of phlebotomy. However, subjects with dysplasia at follow up had significantly higher geometric mean antibody titers for both anti-VCA and anti-EBNA. Subjects with greater than median antibody levels were more likely to progress between examinations, especially in the subgroup with intestinal metaplasia at the time of phlebotomy (odds ratios W ith an estimated 934 000 incident cases and 700 000 deaths worldwide, gastric carcinoma (GC) is the fourth most common cancer, second only to lung cancer in cancerrelated mortality.[(1) GC rates vary widely throughout the world with the highest rates occurring in eastern Asia. Differences in these rates have been attributed to differences in diet and environmental exposures. The pathogenesis of gastric carcinoma is a multistage process affecting the gastric mucosa.(3) For at least intestinal-type GC, there is thought to be a histological progression of precancerous lesions leading up to GC, beginning with superficial gastritis (SG) and advancing through chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia, and finally to GC. More abnormal lesions are associated with an increased risk of GC. In Linqu, China, individuals diagnosed with dysplasia are more likely than those with SG or CAG to develop GC after 5 years. (4) Infection and colonization of the stomach by the bacterium Helicobacter pylori is an important risk factor in the development of most GC, especially non-cardia GC.(5-7) H. pylori infection is thought to cause the development of CAG and IM, (8) and the eradication of H. pylori results in a reduction in the risk of precancerous gastric lesions.(9) A history of H. pylori infection has been found in most GC cases. (7,10) Other infectious agents may also have a role in GC. In particular, the gammaherpesvirus Epstein-Barr virus (EBV) has been implicated by both molecular and serological evidence. EBV nucleic acids are detectable by polymerase chain reaction or in situ hybridization in a significant percentage of GC tumors from many regions of the world, including 16% of GC tumors in North America, (11) 7% in Japan, (12,13) 9% in Russia, (14) and 10% in Kazakhstan.(15) In a prospective study of Japanese Americans, subjects who developed EBV-positive GC had significantly increased antibody titers to EBV viral capsid antigen (VCA) prior to diagnosis.(16) Moreover, in a case-control study from Japan, patients with EBV-positive gastric cancer had...
We evaluated associations between Epstein-Barr virus (EBV) antibody levels and precancerous gastric lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia) in 183 subjects from Linqu, China. Immunoglobulin G antibody titers to EBV nuclear antigen (EBNA) and viral capsid antigen (VCA) were determined by two-fold serial dilution using immunofluorescence assays. Histological progression and regression were assessed by gastroscopic examination at the time of phlebotomy and at follow up 2 years later. Antibody titers did not differ significantly among histological diagnoses determined at the time of phlebotomy. However, subjects with dysplasia at follow up had significantly higher geometric mean antibody titers for both anti-VCA and anti-EBNA. Subjects with greater than median antibody levels were more likely to progress between examinations, especially in the subgroup with intestinal metaplasia at the time of phlebotomy (odds ratios W ith an estimated 934 000 incident cases and 700 000 deaths worldwide, gastric carcinoma (GC) is the fourth most common cancer, second only to lung cancer in cancerrelated mortality.[(1) GC rates vary widely throughout the world with the highest rates occurring in eastern Asia. Differences in these rates have been attributed to differences in diet and environmental exposures. The pathogenesis of gastric carcinoma is a multistage process affecting the gastric mucosa.(3) For at least intestinal-type GC, there is thought to be a histological progression of precancerous lesions leading up to GC, beginning with superficial gastritis (SG) and advancing through chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia, and finally to GC. More abnormal lesions are associated with an increased risk of GC. In Linqu, China, individuals diagnosed with dysplasia are more likely than those with SG or CAG to develop GC after 5 years. (4) Infection and colonization of the stomach by the bacterium Helicobacter pylori is an important risk factor in the development of most GC, especially non-cardia GC.(5-7) H. pylori infection is thought to cause the development of CAG and IM, (8) and the eradication of H. pylori results in a reduction in the risk of precancerous gastric lesions.(9) A history of H. pylori infection has been found in most GC cases. (7,10) Other infectious agents may also have a role in GC. In particular, the gammaherpesvirus Epstein-Barr virus (EBV) has been implicated by both molecular and serological evidence. EBV nucleic acids are detectable by polymerase chain reaction or in situ hybridization in a significant percentage of GC tumors from many regions of the world, including 16% of GC tumors in North America, (11) 7% in Japan, (12,13) 9% in Russia, (14) and 10% in Kazakhstan.(15) In a prospective study of Japanese Americans, subjects who developed EBV-positive GC had significantly increased antibody titers to EBV viral capsid antigen (VCA) prior to diagnosis.(16) Moreover, in a case-control study from Japan, patients with EBV-positive gastric cancer had...
IMPORTANCEThe associations of lifestyle factors with gastric cancer (GC) are still underexplored in populations in China. Long-term nutritional supplementation may prevent GC in high-risk populations, but the possible effect modification by lifestyle factors remains unknown. OBJECTIVE To evaluate how lifestyle factors, including smoking, alcohol intake, and diet, may change the risk of GC incidence and mortality and whether the effects of vitamin and garlic supplementation on GC are associated with major lifestyle factors. DESIGN, SETTING, AND PARTICIPANTS This is a secondary analysis of the Shandong InterventionTrial, a masked, randomized, placebo-controlled trial that aimed to assess the effect of vitamin and garlic supplementations and Helicobacter pylori treatment on GC in a factorial design with 22.3 years of follow-up. The study took place in Linqu County, Shandong province, China, a high-risk area for GC. Data were collected from Jully 1995 to December 2017. Overall, 3365 participants aged 35 to 64 years identified in 13 randomly selected villages who agreed to undergo gastroscopy were invited to participate in the trial and were included in the analysis. Data analysis was conducted from March to May 2019. INTERVENTIONSParticipants received vitamin and garlic supplementation for 7.3 years, H pylori treatment for 2 weeks (among participants with H pylori ), or placebo. MAIN OUTCOMES AND MEASURESThe primary outcomes were GC incidence and GC mortality . We also examined the progression of gastric lesions (1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003) as a secondary outcome. RESULTS Of the 3365 participants (mean [SD] age, 47.1 [9.2] years; 1639 [48.7%] women), 1677 (49.8%) were randomized to receive active vitamin supplementation, with 1688 (50.2%) receiving placebo, and 1678 (49.9%) receiving active garlic supplementation, with 1687 (50.1%) receiving placebo. Overall, 151 GC cases (4.5%) and 94 GC deaths (2.8%) were identified. Smoking was associated with increased risk of GC incidence (odds ratio, 1.72; 95% CI, 1.003-2.93) and mortality(hazard ratio [HR], 2.01; 95% CI, 1.01-3.98). Smoking was not associated with changes to the effects of vitamin or garlic supplementation. The protective effect on GC mortality associated with garlic supplementation was observed only among those not drinking alcohol (never drank alcohol: HR, 0.33; 95% CI, 0.15-0.75; ever drank alcohol: HR, 0.92; 95% CI, 0.55-1.54; P for interaction = .03), and significant interactions were only seen among participants with H pylori (never drank alcohol: HR, 0.31; 95% CI, 0.12-0.78; ever drank alcohol: HR, 0.91; 95% CI, 0.52-1.60; P for interaction = .04). No significant interactions between vitamin supplementation and lifestyle factors were found. (continued) Key Points Question Are lifestyle factors associated with increased risk of gastric cancer (GC), and are they associated with changes in the long-term effects of vitamin and garlic supplementation on GC prevention in high-risk populations in China? Findings In this secondary anal...
IMPORTANCE Metabolic deregulation plays an important role in gastric cancer (GC) development.To date, no studies have comprehensively explored the metabolomic profiles along the cascade of gastric lesions toward GC.OBJECTIVE To draw a metabolic landscape and define metabolomic signatures associated with the progression of gastric lesions and risk of early GC. DESIGN, SETTING, AND PARTICIPANTSA 2-stage, population-based cohort study was initiated in 2017 in Linqu County, Shandong Province, China, a high-risk area for GC. Prospective follow-up was conducted during the validation stage (June 20, 2017, to May 27, 2020). A total of 400 individuals were included based on the National Upper Gastrointestinal Cancer Early Detection Program in China. The discovery stage involved 200 individuals with different gastric lesions or GC (high-grade intraepithelial neoplasia or invasive GC). The validation stage prospectively enrolled 152 individuals with gastric lesions who were followed up for 118 to 1063 days and 48 individuals with GC. EXPOSURES Metabolomic profiles and metabolite signatures were examined based on untargeted plasma metabolomics assay. MAIN OUTCOMES AND MEASURESThe risk of GC overall and early GC (high-grade intraepithelial neoplasia), and progression of gastric lesions. RESULTSOf the 400 participants, 124 of 200 (62.0%) in the discovery set were men; mean (SD) age was 56.8 (7.5) years. In the validation set, 136 of 200 (68.0%) were men; mean (SD) age was 57.5 (8.1) years. Distinct metabolomic profiles were noted for gastric lesions and GC. Six metabolites, including α-linolenic acid, linoleic acid, palmitic acid, arachidonic acid, sn-1 lysophosphatidylcholine (LysoPC)(18:3), and sn-2 LysoPC(20:3) were significantly inversely associated with risk of GC overall and early GC (high-grade intraepithelial neoplasia). Among these metabolites, the first 3 were significantly inversely associated with gastric lesion progression, especially for the progression of
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