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Background: Effective risk prediction models are lacking for personalized endoscopic screening of gastric cancer (GC). We aimed to develop, validate, and evaluate a questionnaire-based GC risk assessment tool for risk prediction and stratification in the Chinese population. Methods: In this three-stage multicenter study, we first selected eligible variables by Cox regression models and constructed a GC risk score (GCRS) based on regression coefficients in 416,343 subjects (aged 40–75 years) from the China Kadoorie Biobank (CKB, development cohort). In the same age range, we validated the GCRS effectiveness in 13,982 subjects from another independent Changzhou cohort (validation cohort) as well as in 5348 subjects from an endoscopy screening program in Yangzhou. Finally, we categorized participants into low (bottom 20%), intermediate (20–80%), and high risk (top 20%) groups by the GCRS distribution in the development cohort. Results: The GCRS using 11 questionnaire-based variables demonstrated a Harrell's C-index of 0.754 (95% CI, 0.745–0.762) and 0.736 (95% CI, 0.710–0.761) in the two cohorts, respectively. In the validation cohort, the 10-year risk was 0.34%, 1.05%, and 4.32% for individuals with a low (≤ 13.6), intermediate (13.7~30.6), and high (≥ 30.7) GCRS, respectively. In the endoscopic screening program, the detection rate of GC varied from 0.00% in low-GCRS individuals, 0.27% with intermediate GCRS, to 2.59% with high GCRS. A proportion of 81.6% of all GC cases was identified from the high-GCRS group, which represented 28.9% of all the screened participants. Conclusions: The GCRS can be an effective risk assessment tool for tailored endoscopic screening of GC in China. Risk Evaluation for Stomach Cancer by Yourself (RESCUE), an online tool was developed to aid the use of GCRS. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal (GI) cancer risk has been associated with metabolic syndrome (MetS), a surrogate indicator for unhealthy lifestyles, and a number of genetic loci, but the combined effect of MetS and genetic variants on GI cancer risk is uncertain. Methods: We included 430,036 participants with available MetS and genotype data from UK Biobank. During the follow‐up time, 5494 incident GI cancer cases, including esophageal cancer, gastric cancer, and colorectal cancer, were identified. We created a GI polygenic risk score (GI‐PRS) for overall GI cancer derived from three site‐specific cancer PRSs. Cox proportional hazards regression was used to estimate the associations of MetS and GI‐PRS with the risk of GI cancer. Results: MetS was significantly associated with 28% increment in GI cancer risk (hazard ratio [HR]MetS vs. non‐MetS: 1.28, 95% confidence interval [CI]: 1.21–1.35, p < 0.0001), whereas a high GI‐PRS (top quintile) was associated with 2.28‐fold increase in risk (HRhigh vs. low: 2.28, 95% CI: 2.09–2.49, p < 0.0001). Compared with participants without MetS and at low genetic risk (bottom quintile of GI‐PRS), those with MetS and at high genetic risk had 2.75‐fold increase in GI cancer risk (HR: 2.75, 95% CI: 2.43–3.12, p < 0.0001). Additionally, MetS in comparison with no MetS had 1.49‰, 2.75‰, and 3.37‰ absolute risk increases in 5 years among participants at low, intermediate (quintiles 2–4 of GI‐PRS) and high genetic risk, respectively, representing the number of subjects diagnosed as MetS causing a new GI cancer case in 5 years were 669, 364, and 296, respectively. Conclusions: Metabolic and genetic factors may jointly contribute to GI cancer risk and may serve as predictors by quantitative measurements to identify high‐risk populations of GI cancer for precise prevention. [ABSTRACT FROM AUTHOR]

Background and aims: Previous studies have reported the association between limited number of Helicobacterpylori (H. pylori) antigens and gastric cancer (GC) risk. The present study evaluated the association between serum antibodies against 15 different H. pylori proteins measured by using multiplex serology assay and GC risk. Methods: We searched PubMed databases, Embase, Web of Science, and Cochrane Library for relevant articles. A meta‐analysis was used to pool studies and to estimate odds ratios (ORs) with 95% confidence intervals (95%CIs) of different H. pylori antigens associated with GC risk. Heterogeneity was investigated using Cochran's Q test and I‐squared statistic. Results: Nine studies were identified, with a total of 3209 GC cases and 6964 controls. Five H. pylori virulence factors were significantly associated with non‐cardia GC risk at p‐value <0.0033 including: CagA (OR = 3.22, 95%CI: 2.10–4.94), HP0305 (OR = 1.72, 95%CI: 1.32–2.25), HyuA (OR = 1.42, 95%CI: 1.13–1.79), Omp (OR = 1.83, 95%CI: 1.30–2.58), and VacA (OR = 2.05, 95%CI: 1.67–2.52). However, none of the 15 antigens was associated with cardia GC risk. In subgroup analysis by ethnicity, we identified 7 antigens associated with the risk of non‐cardia GC among East Asian while only two antigens were identified in European population. Nevertheless, CagA and GroEL showed a stronger association in Caucasian (CagA OR = 5.83, 95%CI: 3.31–10.26; GroEL OR = 3.66, 95%CI: 1.58–8.50) compared with East Asian (CagA OR = 2.20, 95% CI: 1.85–2.61; GroEL OR = 1.47, 95%CI: 1.29–1.68). Conclusions: This study determined that H. pylori infection increases the risk of non‐cardia GC with differential effects by its virulence factors and with different patterns among East Asian and European populations. These results advance the understanding of the effect of H. pylori on GC. [ABSTRACT FROM AUTHOR]