BACKGROUND:Most existing evidence on secondhand smoke (SHS) exposure and lung cancer in never-smoking women comes from case-control studies, while findings from prospective cohort studies remain inconsistent. Regional variation in SHS-associated risk is poorly understood, and the potential impact of reducing SHS exposure in never-smoking women has not been quantified. METHODS:We analyzed data from 20,401 never-smoking women in the Wenling lung cancer screening cohort (Zhejiang, China), applying Cox proportional hazards regression models to evaluate the association between SHS exposure and lung cancer risk. We further conducted a meta-analysis of published studies to examine regional variation and estimated the population attributable fraction (PAF) of SHS exposure for lung cancer incidence in never-smoking women. RESULTS:SHS exposure was associated with an increased lung cancer risk (HR=1.52, 95% CI: 1.19-1.95). Lung cancer risk tended to increase with higher smoking intensity, with a linear trend observed for cigarettes per day, years of smoking, and pack-years of co-residents and colleagues (Poverall<0.05; Pnon-linear>0.05). In meta-analysis, the pooled relative risk was higher in Asia than in Europe and America [RR= 1.31 (95% CI: 1.20-1.43) vs 1.13 (95% CI: 1.04-1.23); Phet = 0.039]. The PAF suggested that 16.9% (95% CI: 11.6%-22.0%) of lung cancer cases among never-smoking women could be attributed to SHS exposure. CONCLUSIONS:SHS exposure is a risk factor for lung cancer in never-smoking women, with stronger effects observed in Asian populations. Reducing SHS exposure could prevent a substantial proportion of lung cancer cases, underscoring the urgent need for strengthened tobacco control policies.

Objective:Lung cancer screening guidelines abroad predominantly rely on smoking pack-years and age, Chinese guidelines uniquely incorporate non-smoking risk factors, though empirical validation remains limited. This study compared low-dose computed tomography (LDCT) screening participation and effectiveness between non-smoking females and males in real-world settings. Methods:This study used data from the Cancer Screening Program in Urban China (CanSPUC) in Zhejiang Province, spanning from April 2019 to December 2024. Eligible participants were aged 45 to 74 and were evaluated for a high risk for lung cancer. We stratified the population into three comparison groups: non-smoking females, non-smoking males and smoking males. Four key screening metrics were compared between groups: LDCT adherence rate, positive rate, lung cancer detection rate and false-positive rate. Multivariable robust (modified) Poisson regression was used to estimate adjusted risk ratios (aRRs) between groups. Results:A total of 88,797 participants aged 45 to 74 years were included in this study, comprising 43,604 non-smoking females and 45,193 males (6988 non-smokers). The overall LDCT participation rate was 61.2%, with a positive rate of 5.6%, lung cancer detection rate was 1.5%, and a false-positive rate of 95.2%. After adjustment for age, BMI, educational level, passive smoking, occupational exposure to hazardous substances, history of tuberculosis; history of COPD; family history of lung cancer, hypertension; hyperlipidemia and diabetes, smoking males showed significantly higher rates than non-smoking females in LDCT adherence (aRR=1.22, 95% CI 1.20-1.24), positive findings (aRR=1.12, 95% CI 1.04-1.20), and lung cancer detection (aRR=1.36, 95% CI 1.17-1.57). Conversely, non-smoking males demonstrated lower adherence (aRR=0.82, 95% CI 0.79-0.85), fewer positive findings (aRR=0.83, 95% CI 0.70-0.98), and reduced lung cancer detection (aRR=0.57, 95% CI 0.37-0.86) compared to non-smoking females. False-positive rates showed no significant differences across groups. During risk stratification of non-smoking females, both passive smoking (aRR=1.46, 95% CI 1.08-2.01) and hormonal abnormalities (aRR=1.39, 95% CI 1.11-1.75) were identified as independent risk factors for lung cancer, with no significant interaction observed between these factors. Multivariable analyses revealed that high-risk non-smoking females with both passive smoking and hormonal abnormalities showed no statistically significant differences in lung cancer detection rates (vs. all males: aRR=0.93, 95% CI 0.77-1.13; vs. smoking males: aRR=0.88, 95% CI 0.72-1.07) or false-positive rates (vs. all males: aRR=0.95, 95% CI 0.85-1.07; vs. smoking males: aRR=0.96, 95% CI 0.85-1.07) compared to male populations. Conclusions:In summary, current lung cancer screening criteria demonstrate limited applicability in female populations, as evidenced by significantly lower LDCT adherence, positive rates, and detection rates among non-smoking females compared to smoking males. Critically, we identified a well-defined subgroup of non-smoking females characterized by combined passive smoking and hormonal abnormalities. This subgroup exhibited screening outcomes that were not statistically significantly different from those observed in male populations. These findings support the development of more precise, risk-stratified screening criteria that better account for sex-specific differences in lung cancer risk and clinical presentation.

Cancer literacy is a crucial component of cancer prevention, and disparities in cancer burden are observed based on socioeconomic status (SES). Evidence on the relationship between SES and cancer literacy among Chinese population is limited. This study aims to evaluate the association between SES disparities and cancer literacy. This multicenter cross-sectional survey included 12 sites in China, employing a multistage proportional stratified cluster random sampling approach. Cancer literacy and sociodemographic information were collected through face-to-face interviews with participants aged 15 to 69 years. Cancer literacy was assessed using a validated questionnaire, with total scores ranging from 0 to 68; a score of 55 or higher indicated adequate cancer literacy. SES was defined by integrating household income, education, and occupation, with levels (low, medium, and high) determined through latent class analysis. Multivariable logistic regression was conducted to examine the association between SES and cancer literacy. Among 4,784 participants, 865 (18.08

Although smoking is a well-established risk factor, lung cancer in never-smokers exhibits distinct epidemiological and biological characteristics. Globally, approximately two-thirds of lung cancer cases in never-smokers occur in females, with a higher prevalence observed in Asian populations. Understanding these epidemiological patterns and specific risk factors holds significant implications for informing effective prevention and control strategies. In addition, low-dose CT screening for never-smoking females remains controversial due to insufficient evidence to support its benefits and unresolved concerns about overdiagnosis. This review provides a comprehensive overview of lung cancer among never-smoking females, synthesizing current evidence on its epidemiology, risk factors, and screening practices, thereby elucidating the multifaceted nature of lung cancer in this population and highlighting its implications for prevention, risk stratification, and future research priorities.

Objective:This study aimed to evaluate the long-term effectiveness of a colorectal cancer (CRC) screening strategy combining fecal immunochemical testing (FIT) and questionnaire-based risk assessment (QRA), and to characterize post-polypectomy CRC risk within this screening framework. Methods:A total of 295,706 participants who underwent FIT or QRA were enrolled in a CRC screening program in China. Those with positive results were classified as high risk and referred for colonoscopy. Absolute risk reductions (ARRs) and numbers needed to screen (NNS) were estimated for CRC incidence and mortality. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs), compared to low-risk non-attenders. Among participants with polyps, post-polypectomy CRC risk was evaluated by comparing index colonoscopy findings with negative findings. Results:During a median follow-up of 11.41 years, 1,267 CRC cases and 387 CRC-specific deaths were identified. Among high-risk individuals, colonoscopy attendance was associated with 10-year ARRs of 0.83% for CRC incidence and 0.31% for CRC mortality, corresponding to NNS values of 121 and 323, respectively. Compared with low-risk colonoscopy non-attenders, high-risk colonoscopy attenders showed no significantly increased CRC incidence over 15 years and had lower CRC-specific mortality at 10 and 15 years, with HRs of 0.59 (95% CI: 0.36-0.97) and 0.57 (95% CI: 0.37-0.88), respectively. In contrast, high-risk colonoscopy non-attenders had markedly increased risks of both CRC incidence (HR=2.79, 95% CI: 2.39-3.25) and mortality (HR=2.82, 95% CI: 2.14-3.71). Individuals with high-risk polyps had a markedly elevated CRC risk as early as 3 years after index colonoscopy (HR=5.75, 95% CI: 1.90-17.36). Conclusions:Within a two-step FIT-QRA screening strategy, colonoscopy attendance among high-risk individuals was associated with long-term benefit and a risk profile closer to that of the low-risk population, whereas individuals with high-risk polyps showed markedly elevated CRC risk from 3 years after polypectomy.

Target trial emulation (TTE) has demonstrated popularity because of its ability to improve the reliability of causal inference from observational data. Nevertheless, knowledge about the current use, potential challenges, and insights of target trials in oncology is scarce. A total of 90 TTE studies in cancer areas were identified through systematic reviews in PubMed and Embase. Among the 54 applications in cancer treatment, registry databases (44.4%) and overall survival (OS, 63.0%) were predominantly used as data sources and primary endpoints, respectively. Approximately 30 (55.6%) of the included TTE cases were associated with immortal time bias, and 21 (38.9%) were associated with prevalent user bias. Among the 21 trials from 13 studies that aimed to calibrate the results from preexisting randomized controlled trials (RCTs), only 42.9% met both statistical agreement and estimate agreement. The availability of fit-for-purpose data sources and uncertainty about result concordance were the main hurdles limiting the quantity and quality of TTE in oncology areas. Promoting regulatory acceptance by initiating special projects could be crucial for the expanded application of real-world data (RWD) using TTE. Potential solutions, such as the integration of electronic medical records at the regional or country level, linkage with insurance claims databases, the modernization of eligibility criteria, the use of OS as the primary endpoint, and other best practices, were recommended for improving the feasibility and quality of oncology TTE.

ObjectiveEvidence is scarce about whether colorectal cancer screening can affect the quality of life of participants, particularly in terms of novel screening strategies in Eastern populations.MethodsFrom 2018 to 2021, the TARGET-C trial randomly allocated 19,373 participants to one of three screening strategies: (A) one-time colonoscopy; (B) annual faecal immunochemical test with positives referred for colonoscopy; and (C) annual risk-adapted screening with low-risk participants referred for faecal immunochemical test and high-risk participants referred for colonoscopy. Two rounds of follow-up after baseline screening were conducted over the 3-year period. Based on the TARGET-C, a EuroQol five-dimensional questionnaire-based quality of life survey was administrated to the participants, and utility scores and related changes were used as the main outcomes.ResultsTaking by-strategy utility scores for participants before being screened at baseline as the comparators (n = 2921), the changes in utility scores after baseline screening were -0.008 (P < 0.050) for strategy A, 0.006 (P < 0.050) for strategy B and 0.000 (P > 0.050) for strategy C, and the overall difference in quality of life changes among the three strategies was significant (P < 0.001). Taking the same comparators as above, the changes in utility scores for participants in the second round of follow-up (n = 9201) were 0.011 (P < 0.050), 0.011 (P < 0.050) and 0.005 (P < 0.050), respectively, and the overall difference was neither clinically meaningful nor statistically significant (P = 0.113).ConclusionsNone of the three colorectal cancer screening strategies had a major effect on the participants' quality of life over the 3 years. Within one round of screening, incorporating risk-adapted screening and/or faecal immunochemical test might offset the quality of life impact from colonoscopy screening.

Colorectal cancer(CRC),the third most common cancer and the second leading cause of cancer-related death globally,is responsible for more than 1.9 million new cases and 0.9 mil-lion deaths reported annually1.

BACKGROUND:China accounts for nearly 30% of global colorectal cancer (CRC) cases but has only 3% screening coverage, underscoring the urgent need to expand coverage. We evaluated the efficacy and cost-effectiveness of extending risk-stratified CRC screening based on the first province-wide, full-coverage initiative in China (2020-2024). METHODS:This population-based study covered 17 780 462 average-risk residents aged 50-74. Those participants were stratified using the Revised Asia-Pacific Colorectal Screening Score (APCS) and fecal immunochemical testing (FIT). High-risk participants (APCS ≥5 or FIT-positive) were referred for colonoscopy. A health care system perspective Markov model simulated a cohort of 100 000 individuals to compare screening strategies by initiation age and frequency. Outcomes included screening yield (participation, detection, and death averted), resource utilization (colonoscopies, costs per lesion detected, and number needed to screen), and cost-effectiveness. Incremental cost-effectiveness ratios (ICERs), benchmarked against three times per capita GDP (USD $ 53 235 in 2023) per quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed. RESULTS:Among 10 364 955 eligible participants, 1 582 606 (15.27%) were high-risk, with 38.92% colonoscopy compliance. Screening detected 59 954 advanced adenomas (AAs) and 5708 CRCs, with 11 and 108 colonoscopies needed per lesion, respectively. The cost per AA and CRC detected was $ 1588 and $ 16 684. All screening strategies were cost-effective regardless of the starting age or frequency, yielding ICERs of $ 6718- $ 21 177 per QALY. Annual screening starting at 40-44 years achieved optimal effectiveness (19 955 QALYs gained, 1126 CRC deaths averted per 100 000). CONCLUSION:This first province-wide, full-coverage screening initiative demonstrates the effectiveness and cost-effectiveness of extending risk-based CRC screening in resource-rich regions of China, supporting expanded coverage and informing policy decisions for CRC prevention in similar settings.

BACKGROUND:Adolescents and young adults (AYAs, 10-24 years) constitute a distinct cancer population in whom malignancy arises during critical life transitions yet leads to substantial long-term morbidity and socioeconomic consequences. However, their global cancer burden and risk-factor profile remain incompletely characterized, especially in low- and middle-income settings. METHODS:We conducted a secondary analysis of the Global Burden of Disease 2021 dataset, synthesizing estimates of cancer incidence, mortality, and disability-adjusted life years (DALYs) for 32 cancer types among AYAs across 204 countries and territories. Temporal trends (1990-2021) and associations with the socio-demographic index (SDI) were evaluated using log-linear and Spearman's correlation analyses. RESULTS:Globally, from 1990 to 2021, AYA cancer incidence rose slightly (+0.12% per year), while mortality and DALY rates declined (-1.02% per year). The fastest-rising incidence involved multiple myeloma (2.39% annually), breast, testicular, thyroid, and prostate cancers, whereas stomach, liver, esophageal, nasopharynx, and lung showed the steepest declines. In 2021, incidence correlated positively with SDI, but mortality and DALY rates correlated negatively. Modifiable risks accounted for 4.32% of DALYs, dominated by unsafe sex (2.54%) in low-SDI regions versus high body mass index (0.83%) and alcohol (0.64%) in higher-SDI settings. CONCLUSIONS:Global AYA cancer epidemiology reveals substantial geographical, temporal, and socioeconomic disparities. Rising incidence and burden of certain cancers highlight unmet prevention and diagnostic needs. Effective interventions, particularly targeting modifiable risks and promoting equitable healthcare access, are essential to reduce the global burden of AYA cancers.

Colorectal cancer (CRC) remains a major global health concern, underscoring the need for reliable biomarkers for diagnosis and prognosis. In this study, untargeted plasma proteomics was conducted across two cohorts comprising 321 participants in the discovery set and 353 in the validation set. Machine learning methods were employed to select biomarkers and develop diagnostic and prognostic models, with performance evaluated by the area under the receiver operating characteristic curve (AUC). An eight-protein panel for CRC and a six-protein panel for advanced adenoma discriminated from healthy controls with AUCs of 0.932 and 0.816 in the validation set, respectively. Additionally, a combined prognostic model incorporating eight proteins and clinical factors predicted 5-year disease-free survival in CRC with an AUC of 0.744 in the validation cohort. Overall, the identified protein biomarkers have the potential to foster the development of effective blood-based tests for early detection and prognostic prediction of CRC.

Abstract Background and aim: Over the past two decades, the incidence of early-onset colorectal cancer (CRC) has risen in several high-income countries. To address this trend, the United States Preventative Services Task Force recommended lowering the starting age for CRC screening from 50 to 45 years based on estimates from microsimulation models. However, real-world evidence on the screening yield across diverse populations remains limited. Methods: A population-based CRC screening program has been implemented since 2020 in a region with high CRC incidence (Zhejiang Province, China). The program primarily targeted individuals aged ​50-74 years but ​also included those aged 40-49​ years. Screening consisted of two-sample fecal immunochemical testing (FIT), with colonoscopy offered to individuals testing positive on either sample. We compared screening outcomes between participants aged 45-49 years and 50-54 years, including: (1) FIT positivity (threshold of 20 μg hemoglobin per gram of feces); (2) colonoscopy completion; and (3) positive predictive values (PPV, cases detected among those with a positive FIT and available colonoscopy) for neoplasia. Advanced neoplasia included CRC, advanced adenoma and advanced serrated lesion. Variables with standardized mean differences greater than 0.1, including sex, fruit intake, and year of participation, were included in the propensity score model for 1:1 matching between age groups. Risk ratios (RRs) were estimated using a Poisson mixed-effects model. Results: After propensity score matching, 89 446 subjects aged 45-49 and 89446 subjects aged 50-54 who completed the FIT test were selected, with comparable baseline characteristics. The FIT positivity in the 45-49 age group was 10.61%, which was lower than 11.02% in the 50-54 age group (RR, 0.96; 95% CI, 0.94-0.99), with similar colonoscopy adherence (46.75% vs 47.43%; RR, 0.99; 95% CI, 0.95-1.03). Compared with the 50-54 age group, the 45-49 age group had significantly lower PPVs for any adenoma (15.82% vs 19.91%; RR, 0.79; 95% CI, 0.72-0.88) and advanced neoplasia (6.06% vs 8.25%; RR, 0.73; 95% CI, 0.63-0.86).In subgroup analyses of 45-49 age group, the PPVs for advanced neoplasia among participants with smoking, BMI ≥28 kg/m2, frequent alcohol drinking, personal history of adenoma or a family history of CRC exceeded that observed in the 50-54 age group. Conclusions: Individuals aged 45-49 years had comparable colonoscopy adherence to those aged 50-54 years but a lower yield for adenomas and advanced neoplasia. Higher yields among younger individuals with risk factors highlight the potential of risk-stratified approaches. These findings contribute population-specific evidence to inform ongoing discussions on optimal screening initiation age, but further longitudinal, cost-effectiveness, and programmatic evaluations are warranted. Citation Format: Le Wang, Chen Zhu, Yu Qiu, Weimiao Wu, Dong Hang, Ni Li, Partha Basu, Lingbin Du. Effectiveness of initiating FIT screening at age 45: Comparative yield with adults aged 50-54 years [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7602.

BACKGROUND:The rising incidence of early-onset colorectal cancer (CRC) has prompted debate over lowering screening initiation age. However, real-world evidence on fecal immunochemical test (FIT)-based screening effectiveness in 45-49 years remains limited. Our study aimed to evaluate screening yield of FIT-based CRC screening between 45-49 and 50-54 years. METHODS:Conducted within a provincial CRC screening program in China, this study employed two-sample FIT screening followed by colonoscopy for positive results. Screening outcomes, including FIT positivity, colonoscopy completion, positive predictive values (PPVs) and detection rates of adenoma and advanced colorectal neoplasia, were compared between participants aged 45-49 and 50-54 years. Robust Poisson regression was used to estimate adjusted risk ratios (aRRs), using 50-54-year-old group as reference. RESULTS:Among 733,137 participants, 89,446 were aged 45-49 years and 643,691 aged 50-54 years. Participants aged 45-49 years had higher FIT positivity (10.61%) and colonoscopy completion (46.75%) than those aged 50-54 years. However, detection rates for advanced neoplasia (0.30% vs. 0.39%; aRR, 0.78; 95% CI, 0.68-0.88) and any adenoma (0.78% vs. 0.95%; aRR, 0.83; 95% CI, 0.77-0.90) were significantly lower in the younger group, with similar results observed for PPVs. Within the 45-49 year group, comparable detection rates to 50-54 year age group were observed among individuals with established risk factors, most notably among smokers (RR, 1.50; 95% CI, 1.22-1.84), frequent alcohol drinkers (RR, 1.33; 95% CI, 1.01-1.75), and males (RR, 1.20; 95% CI, 1.03-1.40). CONCLUSIONS:Overall, adults aged 45-49 years showed higher screening participation but lower screening yield than those aged 50-54 years. These findings highlight the importance of prioritizing individuals with elevated risk profiles for CRC screening in younger populations.

The widespread implementation of low-dose computed tomography (LDCT) has markedly increased the detection of pulmonary nodules, yet their genetic determinants remain poorly understood. We conducted a genome-wide association study (GWAS) of 36 175 LDCT-screened individuals from Zhejiang and Jiangsu provinces in China, assessing fourteen pulmonary nodule phenotypes defined using a convolutional neural network-based computer-aided detection (CNN-CAD) system. We identified eleven independent single-nucleotide polymorphisms (SNPs) at nine loci associated with nodule phenotypes. Functional annotation prioritized six candidate genes with either missense variants or strong colocalization evidence, including TP63 at 3q28, PLA2G4F at 15q15.1, HLA-DRB6 and CYP21A2 at 6p21.32, TNFSF11 at 13q14.11, and TNFRSF11B at 8q24.12. These genes were enriched in pathways related to cell adhesion, chemotaxis, cytokine activity, and lymphocyte activation. Several of the identified variants-associated with non-solid components, nodule size, and the number of positive nodules-were also significantly associated with increased malignancy probability of pulmonary nodules. Genetic correlation analysis revealed a substantial shared genetic basis between purely ground-glass nodules (pGGNs) and lung adenocarcinoma (LUAD) (rg = 0.79; 95% CI, 0.16-1.42; P = 0.014), and Mendelian randomization (MR) further supported a potential causal relationship, with an odds ratio (OR) of 51.1 (95% CI: 1.13-2035.31). These findings offer novel insights into the genetic architecture of pulmonary nodules and highlight a substantial genetic overlap between pGGNs and LUAD, which may inform risk prediction and precision prevention in lung cancer screening.

The concept of field cancerization highlights spatially diffuse, pre-malignant changes in carcinogen-exposed lung tissue, yet current screening rarely captures such effects regionally. This exploratory study aims to quantify field cancerization via lobar-level radiomic clustering and assess its association with lung cancer risk in high-risk smokers. A total of 10,280 male current or former smokers (mean age, 62.1 ± 6.34 years) were enrolled from a high-risk population undergoing lung cancer screening. Unsupervised clustering of CT-derived radiomic features was performed for each lobe. A logistic regression-derived weighted spatial risk score was developed to quantify cumulative lobar risk. Cancer incidence associations were assessed after adjusting for polygenic risk and epidemiological factors, with stratified analyses by genetic risk and smoking duration. Distinct radiomic clusters were observed across all lobes, with the right upper lobe demonstrating a significantly higher lung cancer incidence in the high-risk cluster (0.997

Implementation of a RAP-based risk-adapted screening strategy enables personalized screening initiation, with benefits comparable to those observed in the current 50-54-year age group.

Gastric cancer (GC) is a major public health challenge in China, highlighting the need for effective risk stratification to improve early detection. This study aimed to validate existing GC risk assessment models and develop a locally adapted screening approach for GC and precancerous lesions. From 2022 to 2024, a total of 144,329 participants were recruited through a large multicenter endoscopic screening cohort in Zhejiang Province, China, with baseline data collected via interviews and endoscopic examinations. Participants screened in 2022 were used for model development, whereas those screened during 2023–2024 were used for validation and comparative analyses. Least absolute shrinkage and selection operator regression and logistic regression were used to construct a new model and a weighted point-based risk score. Six previously published models were externally validated for comparison across the validation set. Model performance and clinical utility were assessed and compared using area under the curve (AUC), detection rates, and decision curve analysis for both GC and the composite outcome of GC/high-grade intraepithelial neoplasia (HGIN). A total of 1,419 GC cases were identified in the screening cohort. The newly developed model demonstrated favorable discriminative performance, with an AUC of 0.759 (95

While prior metabolomic genome-wide association studies (mGWASs) have identified numerous metabolite quantitative trait loci (mQTLs) in European populations, their characterization in East Asians-particularly Han Chinese-remains limited. Here, we integrated genomic and metabolomic data to systematically map plasma mQTLs in Han Chinese individuals and investigated their associations with common traits and diseases. Genome-wide association study (GWAS) analyses of 846 plasma metabolites were performed in 495 Han Chinese individuals to identify mQTLs. Causal genes with robust evidence were prioritized via colocalization analysis and fine-mapping. Subsequently, a phenome-wide association study (PheWAS) was performed to explore links between mQTLs and common chronic diseases. Mendelian randomization (MR) analyses were further applied to infer causal relationships between metabolites and common diseases. We identified 232 genome-wide significant mQTLs ( P < 5 × 10 -8), of which 52.6% (122) were novel. Cross-ancestry comparisons revealed 72 novel cohort-specific mQTLs associated with 16 metabolites. Colocalization analysis confirmed 175 high-confidence gene-metabolite pairs with shared genetic drivers. PheWAS linked 118 mQTLs to 39 diseases across 11 clinical categories. MR analyses revealed seven putatively causal metabolite-disease relationships, including one for asthma, two for type 2 diabetes, and four for inflammatory bowel disease. Our study delineates the genetic architecture of the plasma metabolome in the Han Chinese population, uncovering novel causal associations between metabolite levels and diseases such as asthma, type 2 diabetes, and inflammatory bowel disease.

Accurate identification of individuals at high risk of gastric cancer (GC) remains a major challenge for effective screening. We aimed to identify plasma proteomic signatures and develop a risk prediction model for GC risk stratification. Plasma proteomic profiling was performed using liquid chromatography–tandem mass spectrometry in a case–control discovery set (100 GC cases and 94 controls). Candidate proteins were evaluated in 52,552 UK Biobank participants with a median follow-up of 13.63 years, during which 92 incident GC cases were identified. Risk models integrating clinical, genetic, and proteomic factors were developed using LASSO-penalized Cox regression with stability selection and internally validated using bootstrap resampling. Among 2306 differentially expressed proteins in discovery, 25 were replicated in validation at nominal significance (P < 0.05) with consistent directions. Two proteins (CTSD and GGH) remained significant after false discovery rate correction. A primary proteomic model (clinical factors plus five proteins) improved discrimination versus clinical model (optimism-corrected C-index: 0.745 vs. 0.732, P = 0.046). Risk stratification revealed a clear GC risk gradient: hazard ratios were 6.08 (95

BackgroundAdherence to colorectal cancer (CRC) screening remains suboptimal in many countries, reducing its cost-effectiveness. This study aimed to evaluate how multistage uptake rates influence the health benefit and cost-effectiveness of various CRC screening strategies in the Chinese population, incorporating both traditional and emerging screening methods.Methods and findingsWe developed a multistate Markov model (CRC-SIM) to evaluate the impact of multistep uptake on CRC screening. A hypothetical cohort of 100,000 individuals aged 40 was simulated and followed until 79 or death. Two-step screening strategies were modeled: initial screening followed by colonoscopy after a positive result. Traditional initial screening methods include: questionnaire-based risk assessment, fecal immunochemical test (FIT), and questionnaire combined with FIT; Non-invasive biomarker-based initial strategies include a hypothetical test meeting the minimum standards of China National Medical Products Administration (NMPAmin), multitarget stool DNA (mt-sDNA) test, and blood-based strategies. All strategies were modeled as one-time screenings, with outcomes projected for CRC cases, deaths, quality-adjusted life years (QALYs), and lifetime costs. Incremental cost-effectiveness ratios (ICERs) were calculated, and a cost-effectiveness heatmap was conducted to assess the impact of multistep uptake (modeled in 10% steps) on economic outcomes. All strategies reduced CRC cases, deaths and increased QALYs compared to no screening, with biomarker-based strategies outperforming the traditional methods at the same uptake level (e.g., questionnaire combined with FIT prevented 224 (95% confidence interval (CI) [157, 292]) CRC cases and 151 (95% CI [109, 195]) deaths, whereas NMPAmin prevented 312 (95% CI [257, 360]) cases and 210 (95% CI [175, 241]) deaths at 100% uptake). The cost-effectiveness heatmap indicated that each 10% increase in initial and follow-up colonoscopy uptake improved ICERs in a non-linear pattern. The questionnaire combined with FIT was the most cost-effective strategy (ICER = $2,413 per QALY gained). Non-invasive biomarker-based tests were not cost-effective compared with the combined questionnaire and FIT strategy under current assumptions of test costs and identical uptake rate. Threshold analysis showed that non-invasive biomarker-based screening would become cost-effective if test costs fell below $131.7 or colonoscopy uptake increased to at least 70% for NMPAmin and 50% for blood-based tests and mt-sDNA. Limitations include the assumption of a one-time screening scenario; future iterations of the model and merging evidence in repeated screening will address these limitations.ConclusionImproving screening participation could enhance health benefits and cost-efficiency in CRC screening. Questionnaire-based risk assessment combined with FIT was a cost-effective strategy in China, whereas non-invasive biomarker-based methods require cost reduction and higher uptake to justify adoption. These findings provide evidence for policymakers to optimize CRC screening programs.