Abstract Lung cancer has a 29% survival rate, with nearly half detected at stage 4. Survival increases to 65% with early-stage diagnosis, yet only 28.1% are diagnosed early. Cardiovascular and respiratory comorbidities coexist with lung cancer and may affect detection and prognosis. Metabolic syndrome (MetS), characterized by central adiposity, hypertension, dysglycemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol, has been associated with lung cancer incidence and mortality. We estimated associations between MetS and lung cancer incidence and mortality and examined study-level heterogeneity. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020, we searched CINAHL, Web of Science, and PubMed (2000–March 2025) for adult (≥18 years) studies reporting quantitative associations between MetS and lung cancer outcomes. Two reviewers independently screened studies and extracted design, population, MetS definitions, outcomes, effect estimates, and covariates. Random-effects meta-analyses and sensitivity analyses were conducted. Study quality was assessed using National Heart, Lung, and Blood Institute tools; funnel plots and the Egger test evaluated small-study effects. Of 163 full-text articles, 11 contributed to the incidence analysis and 4 contributed to the mortality analysis. MetS was associated with higher lung cancer incidence [pooled hazard ratio (HR), 1.18; 95% confidence interval (CI), 1.04–1.33; P = 0.010]. Among good-quality studies with thorough smoking adjustment, the HR was 1.15 (95% CI, 1.04–1.28). Lung cancer mortality was not significantly associated with MetS. Although pooled findings indicate higher lung cancer incidence among individuals with MetS, variation in smoking adjustment precludes causal inference. Future prospective cohorts across diverse populations and settings should use standardized MetS definitions and detailed smoking histories and assess whether MetS can provide a meaningful window for lung cancer screening and early intervention. Prevention Relevance: MetS was associated with a significantly and likely increased lung cancer incidence. However, inadequate smoking adjustment precludes causal inference. As MetS is modifiable, this association may inform prevention during lung cancer screening. Cohort studies with detailed smoking histories are needed to assess causality.
Abstract Barrett's esophagus is the established precursor of gastroesophageal adenocarcinoma, yet most cases are diagnosed outside surveillance. The study investigated demographic, life-style, and genetic contributions to disease stage and progression Barrett's esophagus. Data from 870 participants in the prospective, multicenter BarrettNET registry (10-year follow-up period) were analyzed. Epidemiological data (smoking, alcohol, physical activity, diet, BMI, reflux symptoms) were collected via standardized questionnaires; dietary quality was assessed with a validated nutrition score. Multivariable logistic regression identified factors associated with advanced disease at diagnosis (non-dysplastic disease versus dysplasia or cancer); progression was evaluated using Firth penalized logistic regression. In a genotyped subgroup (739 participants), weighted polygenic risk scores from 41 variants were included as a sensitivity analysis. Among 598 patients with non-dysplastic disease, 116 with dysplasia, and 156 with cancer, older age (OR 1.03, 95% CI 1.01–1.04), male sex (OR 1.92, 95% CI 1.28–2.90), and smoking (OR 1.64, 95% CI 1.15–2.35) were associated with advanced disease. Of 21 participants who progressed during follow-up, older age (OR 1.06, 95% CI 1.02–1.11) and smoking (OR 4.31, 95% CI 1.62–11.47) were associated with progression, whereas reflux symptoms were associated with lower odds (OR 0.36, 95% CI 0.15–0.84; apparent AUC 0.825). Dietary factors and polygenic risk scores showed no independent association with either outcome and did not improve prediction. Age, male sex, and smoking predicted advanced disease and progression in Barrett's esophagus, while currently available polygenic risk scores added little predictive value, supporting lifestyle-based approaches to risk stratification.
Abstract Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second-leading cause of US cancer death by 2030, and survival is dominated by stage at diagnosis: roughly 44% at five years for localized disease versus about 3% with distant metastases. Only about 15% of cases are detected while localized, surgery reaches a minority of patients, and no validated screening test exists for average-risk adults. This topical review examines the biologic, clinical, economic, psychological, equity, and therapeutic evidence bearing on where scarce resources should be directed. The long interval between initiating mutation and invasive disease provides a mechanistic rationale for prevention and interception, and the modifiable exposures of obesity, tobacco, type 2 diabetes, and alcohol act largely within that window. We consider innovations that extend prevention beyond lifestyle advice—incretin-based weight management, risk stratification anchored in new-onset diabetes and biomarkers, and immunoprevention—together with early-onset disease, implementation and policy, and the barriers and evidentiary limits that temper these arguments. We propose a three-tier framework of primary prevention, early detection in high-risk groups, and therapy, and argue that research, policy, and clinical investment should be weighted upstream, because every case prevented spares the cost, capacity, and suffering that the downstream tiers must otherwise absorb.
Abstract The metabolic reprogramming taking place during early lung adenocarcinoma (LUAD) progression remain poorly understood. While early-stage LUAD frequently demonstrates low 18F-2-fluorodeoxyglucose (18FDG) uptake on positron emission tomography (PET), it is unclear whether this reflects metabolic quiescence or alternative glucose utilization pathways. We hypothesized that early lesions are metabolically active but preferentially utilize sodium-glucose cotransporter 2 (SGLT2), a non-canonical glucose transporter with low 18FDG affinity. This study investigates metabolic activity in early-stage LUAD and glucose transporter expression patterns across the adenocarcinoma spectrum. LDH, SGLT2 and GLUT1 expression were evaluated by immunohistochemistry in human lung cancers and compared with normal lung and benign inflammation. Expression levels were correlated with structural and radiologic features including tumor size, invasion, histology, radiographic features and PET avidity. Glycolysis was elevated in premalignant and early LUAD as indicated by LDH expression. SGLT2 was highly expressed in preinvasive and minimally invasive LUAD compared to normal lung and invasive tumors. Conversely, GLUT1 was upregulated in invasive, high-grade tumors. Radiographically, SGLT2 expression was associated with subsolid nodules and low PET avidity, while GLUT1 expression was higher in nodules with a solid component and high 18FDG avidity. Notably, SGLT2 was not elevated in inflammatory lesions compared to normal lung, unlike GLUT1, which was frequently upregulated in inflammation. Early lung adenocarcinoma lesions exhibit aerobic glycolysis despite low FDG avidity and preferentially utilize SGLT2-mediated glucose uptake. These findings highlight a distinct metabolic profile in early LUAD and underscore the need for alternative imaging modalities to enhance the detection of early lesions.
Abstract Lymphoma constitutes a substantial and increasing burden of hematologic malignancy in Thailand and globally, whereas its etiology remains incompletely characterized. Occupational factors have been implicated in lymphomagenesis; however, evidence from developing countries remains limited, particularly with respect to lymphoma heterogeneity by cell of origin. A matched case–control study was conducted to examine associations between occupational categories and lymphoma risk within a cell-of-origin framework. Occupational categories were defined a priori based on epidemiologic evidence and occupational carcinogen classifications of the International Agency for Research on Cancer. The analysis included 592 matched case–control pairs and used conditional logistic regression to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CI). Diffuse large B-cell lymphoma was the most frequent histologic subtype. Agricultural occupations, including agricultural workers, gardeners, and livestock handlers, were associated with increased overall lymphoma risk after adjustment for potential confounders (AOR = 1.41; 95% CI, 1.04–1.90). In prespecified subgroup analyses by cell of origin, associations were observed for B cell–derived malignancies, including combined B-cell non-Hodgkin lymphoma (B-cell NHL) and Hodgkin lymphoma (AOR = 1.50; 95% CI, 1.04–2.15) and B-cell NHL alone (AOR = 1.63; 95% CI, 1.09–2.43). Longer duration of agricultural work and initiation of agricultural work during childhood were also associated with increased lymphoma risk. These findings provide epidemiologic evidence of an association between agricultural occupation and lymphoma, with similar associations observed in analyses of B cell–derived malignancies. The results support further investigation of specific agricultural exposures and may inform occupational cancer surveillance and prevention in agricultural populations. Prevention Relevance: Using a cell-of-origin framework, this study identified an association between agricultural work and lymphoma, with similar associations observed for B cell–derived malignancies in Thailand. These findings provide cell lineage–specific evidence from Southeast Asia and may inform occupational cancer surveillance and context-specific prevention for agricultural workers with complex occupational exposures.
