Wen-Qing Li

Background: Helicobacter pylori eradication prevents gastric cancer. Screen-and-treat for H. pylori is recommended in high-burden regions; household clustering has motivated family-based screening. We aimed to quantify household and community contributions to incident infection and compare H. pylori screening strategies in China, which bears the world’s largest GC burden. Methods: We developed HALT-Hp, an individual-based transmission model representing household and community transmission, calibrated and validated against Chinese demographic, household, H. pylori prevalence, and family-clustering data. We reconstructed transmission during 1990-2023 and evaluated sustained family-index opportunistic screening and one-off organised screening strategies for 2025-2050. Efficiency was assessed using the number needed to screen (NNS) per infection treated and per new infection averted. Findings: Household transmission accounted for most incident infections, declining from 67·7% (95% credible intervals 41·4%, 75·9%) in 1990-1994 to 58·1% (34·2%, 68·5%) in 2020-2023. Prevalence declined from 45·7% in 1990 to 35·5% in 2023 and was projected to reach 31·0% by 2050 without intervention, 30·0% with family-index opportunistic screening and 7·9% after one-off screening of adults aged 18–80 years. Screening ages 40–59 years was most efficient for case detection (NNS 2·3 per infection treated) and overall (NNS 2·2 per infection treated or averted), whereas screening ages 18–39 years was most efficient for preventing transmission (NNS 22·9 per new infection averted). Adding household tracing improved detection efficiency only when index screening targeted adults aged 18–39 years and did not improve transmission-prevention efficiency in either strategy. Interpretation: Household transmission remained predominant, but family-index opportunistic screening was projected to have limited population-level impact. Adding household tracing to organised screening does not consistently improve efficiency.

Background and Objectives: Smoking is a major modifiable risk factor for upper gastrointestinal cancers (UGIC), particularly in China. This study investigated temporal trends, demographic patterns, and future projections of smoking‐attributable UGIC mortality globally and nationally. Methods: We extracted data from the Global Burden of Disease 2021. Joinpoint regression was used to assess trends in smoking‐attributable UGIC mortality rates and absolute deaths. Age‐period‐cohort (APC) model was applied to evaluate effects brought by age groups and birth cohort. Decomposition analysis quantified contributions of aging, population growth, and epidemiologic shifts to mortality changes. Bayesian APC (BAPC) model projected mortality trends to 2030. Results: At the population level, smoking is more strongly associated with esophageal cancer than gastric cancer. Although smoking‐attributable mortality rates of both esophageal and gastric cancers declined globally and in China, the decline was more pronounced for gastric cancer than for esophageal cancer (AAPC: −2.594 vs. −1.229 globally; −2.297 vs. −1.491 in China; both p < 0.001). However, trends in absolute deaths differed by cancer type and geography: smoking‐attributable esophageal cancer deaths increased globally and in China, whereas smoking‐attributable gastric cancer deaths increased in China but remained stable globally. APC analysis revealed the most significant drop among young adults aged 35–44, but mortality trends plateaued or increased in older individuals. In contrast, esophageal cancer mortality is expected to remain elevated through 2030, with an estimated 263,219 deaths globally including 187,567 in China. Conclusions: Despite declining mortality rates, the absolute number of smoking‐related UGIC deaths remains substantial and is rising in China due to demographic momentum. Greater reductions were seen among young individuals and females. These ecological findings underscore the importance of strengthening tobacco‐control policies to mitigate the population‐level burden attributable to smoking, particularly within high‐risk populations.

Background: Previous studies have suggested a possible association between Helicobacter pylori ( H. pylori ) infection and an increased risk of colorectal cancer (CRC). Objective: We examined the associations of H. pylori infection and H. pylori treatment with incident CRC risk and evaluated whether these associations were modified by genetic susceptibility. Design: This study was based on two randomised trial cohorts: the Shandong Intervention Trial (SIT; n=3365; 1995–2024) and the Mass Intervention Trial in Linqu, Shandong Province (MITS; n=180 284; 2011–2024). Within MITS, we further conducted a case-cohort study to assess CRC risk according to seropositivity for H. pylori virulence factors and host genetic predisposition. Results: Compared with H. pylori -negative individuals, H. pylori -positive individuals who did not receive antibiotic treatment had a significantly higher risk of CRC (SIT: HR=2.96, 95% CI 1.30 to 6.71; MITS: HR=1.27, 95% CI 1.04 to 1.55). The increased risk was particularly evident among individuals seropositive for four H. pylori -specific antigens (CagA, HpaA, Omp and HP0305) and those at high genetic risk (top decile of the Polygenic Risk Score). In SIT, H. pylori treatment was associated with a significantly reduced CRC risk over 29.4 years of follow-up (HR=0.47, 95% CI 0.22 to 0.99), with a greater reduction observed among participants with successful eradication (HR=0.38, 95% CI 0.15 to 0.94). In MITS, no overall benefit was observed 13.8 years after treatment (HR=1.17, 95% CI 0.95 to 1.43). However, a protective effect was apparent among individuals at high genetic risk and among those seropositive for key H. pylori -specific antigens. Conclusion: In post hoc observational analyses of two established trial cohorts, H. pylori infection was associated with an increased risk of CRC. H. pylori treatment reduced CRC risk in SIT, whereas in MITS, the benefit appeared to be limited to individuals at high genetic risk or those infected with specific virulence factor subtypes.

Allostatic load (AL) is a composite measure of cumulative physiological burden from chronic stress, quantifying multisystem dysregulation. Whether AL may alter the risk of overall, cause-specific mortality, and premature mortality remains unclear. We analyzed UK Biobank participants aged 40-69 years (mean 56.6; 53.8% female) with complete data of AL metrics. AL was assessed by integrating 12 commonly applied metrics covering cardiovascular, metabolic, immune, and kidney systems (score range: 0-12), with higher scores indicating greater physiological dysregulation. Associations of AL scores with mortality from all cause and cause-specific mortality were examined. Stratified analyses assessed effect modification by premature mortality (< 70 years at death) and age at recruitment. Over a median follow-up of 15.4 years, 39,804 deaths were recorded, including 14,852 from cancer, 7118 from cardiovascular disease, 1938 from respiratory disease, and 1521 from digestive disease. Higher AL scores were significantly associated with increased risks of all-cause and cause-specific mortality in a dose-response manner (all P-trend < 0.001). Among specific causes, each one-point rise in AL score yielded stronger associations with digestive disease mortality (subdistribution hazard ratio [sHR] = 1.25, 95% confidence interval [CI]: 1.21-1.29) and cardiovascular disease mortality (sHR = 1.20, 95% CI: 1.18-1.21) than for cancer mortality (sHR = 1.08, 95% CI: 1.07-1.09) and respiratory disease mortality (sHR = 1.11, 95% CI: 1.09-1.14). Age significantly modified these associations (all P-interaction < 0.01), with higher HRs for premature mortality (age at death < 70 years) or younger individuals (age at enrollment < 50 years). Higher AL scores were associated with increased risks of all-cause and cause-specific mortality. Such associations were particularly pronounced for digestive and cardiovascular disease mortality, and appeared stronger for premature deaths and among younger individuals. These findings suggest that AL may serve as a marker of early physiological dysregulation and may help identify individuals at elevated risk of premature mortality.

Cancer is a major public health threat, leading to substantial mortality and disease burden worldwide. Carcinogenesis is modulated by a multitude of genetic, environmental, and lifestyle-related determinants, among which diet constitutes a critical modifiable risk factor. In recent years, Mediterranean diet (MedDiet), characterized by high intake of plant foods and low intake of red meat and processed foods, has garnered widespread attention for its potential health benefits. This narrative review synthesizes recent epidemiological studies, meta-analyses, and mechanistic research on the association between MedDiet and cancer. Current evidence generally suggests an inverse association between MedDiet adherence and overall cancer risk, particularly for colorectal and gastric cancers, whereas findings regarding other cancers remain controversial. Potential underlying mechanisms of MedDiet include the modulation of chronic inflammation, oxidative stress, metabolic dysregulation, gut microbiota, and epigenetics. In addition, key dietary components such as unsaturated fatty acids, polyphenols, and dietary fiber may play important roles in cancer prevention. However, variable exposure definitions, dietary measurement bias, between-site cancer heterogeneity, and regional disparities in dietary profiles limit the interpretation and generalizability of existing findings. Particularly, most available evidence has been derived from European and American populations, and its applicability to Asian and other non-Mediterranean populations requires further validation. Moreover, the predominance of observational studies limits causal inference. In the future, research should prioritize high-quality prospective and interventional studies, alongside multi-omics studies on mechanisms, to clarify the real effects and key biological mechanisms of MedDiet, thereby providing a more reliable scientific basis for cancer prevention and dietary guidance.

Background and Aims: Helicobacter pylori ( H. pylori ) is a major risk factor for gastric cancer (GC) and multiple other chronic illnesses. Host genetic factors influence the susceptibility to H. pylori infection, as evidenced by elevated concordance in monozygotic twins and racial disparities independent of socioeconomic status. Leveraging meta‐analyses and in silico functional annotation, we investigated host genetic susceptibility to H. pylori infection, and to examine how these variants may influence gastric cancer (GC) risk. Methods: Meta‐analyses were performed on 25 candidate genetic variants that had been investigated for the association with H. pylori infection in at least three studies, under five genetic models (allelic, dominant, recessive, homozygous, and heterozygous). Meta‐analyses on genome‐wide variants were conducted using the allelic model. The Bayesian False‐Discovery Probability method and Venice criteria were used to assess genetic association credibility. The Genotype‐Tissue Expression (GTEx) and eQTLGen databases were used for cis‐expression quantitative trait locus (eQTL) analysis. Differential gene expression in H. pylori ‐positive ( n = 61) vs. ‐negative ( n = 17) samples, and GC ( n = 414) vs. non‐GC tissues ( n = 210) was analyzed leveraging The Cancer Genome Atlas, GTEx, and in‐house RNA‐sequencing data. Results: From a total of 103 studies for systematic review, meta‐analyses based on 83 studies identified 47 variants across 18 loci associated with H. pylori susceptibility. These loci encompassed 29 cis‐eQTLs affecting expression of 42 genes. Of them, seven genes at three loci—4p14 ( TLR10 , TLR6 , KLHL5 , TMEM156 ), 6p21.33 ( HLA‐DRB6 , C4B ), and 14q32.2 ( WARS )—were consistently upregulated in H. pylori infection and GC, which may contribute to H. pylori infection‐related GC development. Conclusion: Host genetic predisposition alters the odds of H. pylori infection, demonstrating the importance of host‐pathogen crosstalk in infection dynamics and subsequent gastric carcinogenesis.