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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]

Background and Aim: Helicobacter pylori (H. pylori) infection rates have been changing with different populations and geographic areas. We systematically evaluated the longitudinal trends in H. pylori prevalence in China over the past decades. Methods: We performed a systematic review of literature reporting the prevalence of H. pylori infection in mainland China from 1990 to 2019 in the PubMed and China National Knowledge Infrastructure databases. We conducted a meta‐analysis of qualified studies using a random effects model to estimate the pooled prevalence with a 95% confidence interval (95%CI). Results: A total of 412 eligible studies with 1 377 349 subjects were included. The pooled H. pylori prevalence was 44.2% (95%CI: 43.0–45.5%) in mainland China, with an estimated 589 million individuals infected with H. pylori. The prevalence was relatively high in the Northwest (51.8%, 95%CI: 47.5–56.1%), East (47.7%, 95%CI: 45.4–50.0%), and Southwest China (46.6%, 95%CI: 42.1–51.1%). The prevalence significantly decreased from 58.3% (95%CI: 50.7–65.5%) in the period 1983–1994 to 40.0% (95%CI: 38.2–41.8%) in the period 2015–2019. The prevalence increased with age, ranging from 28.0% (95%CI: 23.9–32.5%) in children and adolescents to 46.1% (95%CI: 44.5–47.6%) in adults. Conclusion: Although the burden of H. pylori infections is still huge in China, the infection rate has been decreasing over the past decades. Targeted H. pylori eradication strategies may be considered in areas or populations with a high incidence of gastric cancer. [ABSTRACT FROM AUTHOR]

Genome‐wide association studies (GWAS) have identified multiple gastric cancer risk loci and several protein‐coding susceptibility genes. However, the role of long‐noncoding RNAs (lncRNAs) transcribed from these risk loci in gastric cancer development and progression remains to be explored. Here, we functionally characterize a lncRNA, lncPSCA, as a novel tumor suppressor whose expression is fine‐regulated by a gastric cancer risk‐associated genetic variant. The rs2978980 T > G change in an intronic enhancer of lncPSCA interrupts binding of transcription factor RORA, which down‐regulates lncPSCA expression in an allele‐specific manner. LncPSCA interacts with DDX5 and promotes DDX5 degradation through ubiquitination. Increased expression of lncPSCA results in low levels of DDX5, less RNA polymerase II (Pol II) binding with DDX5 in the nucleus, thus activating transcription of multiple p53 signaling genes by Pol II. These findings highlight the importance of functionally annotating lncRNAs in GWAS risk loci and the great potential of modulating lncRNAs as innovative cancer therapy. Synopsis: The long non‐coding RNA lncPSCA is a tumor suppressor encoded at the 8q24.3 gastric cancer risk locus. LncPSCA promotes DDX5 degradation, reduces RNA polymerase II interactions with DDX5, and activates transcription of multiple p53 signaling genes. LncRNA lncPSCA is a novel tumor suppressor at the 8q24.3 gastric cancer risk locus.The rs2978980 risk polymorphism interrupts RORA binding to a lncPSCA enhancer and down‐regulates its expression in an allele‐specific manner.LncPSCA interacts with DDX5 and promotes DDX5 degradation via ubiquitination. [ABSTRACT FROM AUTHOR]