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Premature mortality trends in 183 countries by cancer type, sex, WHO region, and World Bank income level in 2000–19: a retrospective, cross-sectional, population-based study
Abstract
Background
Cancer is a leading cause of mortality worldwide. By 2040, over 30 million new cancers are predicted, with the greatest cancer burden in low-income countries. In 2015, the UN passed the Sustainable Development Goal 3.4 (SDG 3.4) to tackle the rising burden of non-communicable diseases, which calls for a reduction by a third in premature mortality from non-communicable diseases, including cancer, by 2030. However, there is a paucity of data on premature mortality rates by cancer type. In this study, we examine annual rates of change for cancer-specific premature mortality and classify whether countries are on track to reach SDG 3.4 targets.
Methods
This is a retrospective, cross-sectional, population-based study investigating premature mortality trends from 2000–19 using the WHO Global Health Estimates data. All cancers combined and thirteen individual cancers in 183 countries were examined by WHO region, World Bank income level, and sex. The risk of premature mortality was calculated for ages 30–69 years, independent of other competing causes of death, using standard life table methods. The primary objective was to compute average annual rate of change in premature mortality from 2000 to 2019. Secondary objectives assessed whether this annual rate of change would be sufficient to reach SDG 3.4. targets for premature mortality by 2030.
Findings
This study was conducted using data retrieved for the years 2000–19. Premature mortality rates decreased in 138 (75%) of 183 countries across all World Bank income levels and WHO regions, however only eight (4%) countries are likely to meet the SDG 3.4 targets for all cancers combined. Cancers where early detection strategies exist, such as breast and colorectal cancer, have higher declining premature mortality rates in high-income countries (breast cancer 48 [89%] of 54 and colorectal cancer 45 [83%]) than in low-income countries (seven [24%] of 29 and four [14%]). Cancers with primary prevention programmes, such as cervical cancer, have more countries with declining premature mortality rates (high-income countries 50 [93%] of 54 and low-income countries 26 [90%] of 29). Sex-related disparities in premature mortality rates vary across WHO regions, World Bank income groups, and by cancer type.
Interpretation
There is a greater reduction in premature mortality for all cancers combined and for individual cancer types in high-income countries compared with lower-middle-income and low-income countries. However, most countries will not reach the SDG 3.4 target. Cancers with early detection strategies in place, such as breast and colorectal cancers, are performing poorly in premature mortality compared with cancers with primary prevention measures, such as cervical cancer. Investments toward prevention, early detection, and treatment can potentially accelerate declines in premature mortality.
Funding
WHO.
... Delays in treatment worsen results even more. According to a study, the patients with low SEP die eight months sooner and begin treatment later (91 days versus 76 days for endometrial cancer, for example) [20]. These findings are supported by higher mortality rates (186.20-189.80), ...
... Additionally, access barriers caused gaps in prostate and melanoma, with 50% of melanoma cases being critical [13]. Countries with primary preventative programs for cancers, such as cervical cancer, have seen lower rates of premature mortality [20]. ...
Simple Summary: Improvements in cancer screening, diagnosis, and treatment have enhanced survival rates; nevertheless, this progress is not consistent, especially in areas marked by adverse social determinants. Counties characterized by poor job rates and insufficient educational attainment demonstrate heightened age-adjusted cancer mortality rates; hence, cancer survivability is influenced by socioeconomic determinants including geographic location, racial and cultural diversity, and limited access to healthcare.
Abstract: Background: This study aims to evaluate the potential relationship between county-level social determinants of health (SDOH)-specifically education and job status-and cancer mortality. Methods: We utilized Social Determinants of Health (SDOH) data from the Agency for Healthcare Quality (AHRQ) 2015 county database for a cross-sectional study investigating the primary independent variables-low education and low employment status-and the outcome of cancer mortality. Results: Out of 3134 counties, 906 exhibited poor employment levels, while 467 showed low educational attainment. The age-adjusted cancer death rate for non-low-education counties was 172.90 [157.00, 188.40], but for low-education counties it was 186.20 [161.72, 209.33], p < 0.001. Conversely, this was 169.15 [154.00, 183.50], compared to 189.80 [171.90, 207.10], p < 0.001, for counties with low employment. The adjusted analysis indicated that counties with low education levels were correlated with elevated age-adjusted cancer mortality (7.68, 95% CI: 5.06-10.31), and similarly, counties with low employment rates were linked to increased age-adjusted cancer mortality (4.69, 95% CI: 2.58-6.79). Conclusions: Our findings indicate that counties characterized by low educational attainment and poor employment levels are associated with elevated age-adjusted cancer death rates.
... Demographic projections suggest a concerning trend, indicating that by the year 2050, the annual incidence of new cancer cases is expected to reach 35 million, representing a 77% increase compared to the figures reported in 2022 [1]. Evidence suggests that accurate diagnosis during the early stages of tumor development significantly reduces cancer mortality rates [7][8][9]. However, current diagnostic approaches primarily rely on techniques such as endoscopy, computed tomography (CT), X-ray imaging, magnetic resonance imaging (MRI), and pathological tissue biopsy [10][11][12]. ...
... Currently, the diagnosis of prostate cancer mainly includes early screening, imaging examination, and histological biopsy [79,80]. However, imaging and histological biopsies are often radioactive, invasive or highly resource-intensive, limiting their feasibility for widespread use, particularly in resource-constrained communities or areas [8,81,82]. More importantly, because of the slow progression and asymptomatic nature, many patients are diagnosed at an advanced stage when symptoms become pronounced and imaging or biopsies are typically necessary [83][84][85][86]. ...
Urogenital system tumors include prostate cancer, bladder cancer, ovarian cancer, and other very common solid tumor diseases with high morbidity and high mortality. The unique physiological and anatomical features of the urogenital system render it particularly amenable to the application of tissue imaging techniques for diagnostic purposes. The advancement of aggregation‐induced emission (AIE) materials has addressed the limitations associated with conventional fluorescent materials that are prone to aggregation‐caused quenching. This advancement has facilitated the development of innovative AIE fluorescent materials characterized by enhanced photostability, an increased signal‐to‐noise ratio, and improved imaging quality. This article reviews the research progress of AIE biosensors in the diagnosis of urogenital tumors. It mainly involves biomarker diagnostic in vitro and fluorescence imaging in urogenital solid tumors such as prostate cancer, uterine cancer, bladder cancer, and ovarian cancer, which are based on AIE biosensors. In addition, a comprehensive description of AIE biosensors’ synthesis and application strategies is provided. This includes a detailed elucidation of in vitro diagnostic platforms and intracellular imaging mechanisms based on the basic principles of AIE, accompanied by a presentation of quantitative analysis and cell imaging results. In addition, the limitations, challenges and suggestions of AIE biosensors application in the field of tumor diagnosis are summarized, and the development prospect of AIE biosensors in the field of tumor diagnosis is prospected. This article reviews the application of AIE biosensors in the diagnosis of urogenital tumors, and also provides a catalyst for exploring the characteristics of AIE biosensors and its wide application in the field of disease diagnosis.
... Furthermore, the World Health Assembly elevated cancer care on the global health agenda in 2017 by passing resolution 70.12, which allowed WHO to prioritize cancer prevention and control programs. (Murthy et al., 2024). The five most common dietary and behavioral hazards contribute to almost one-third of deaths caused by cancer one of which is low fruit and vegetable intake. ...
Breast cancer poses a global health challenge and requires innovative approaches for prevention and treatment. Phytochemicals have gained attention for their potential anti-cancer properties by offering promising therapeutic interventions with their many advantageous effects and activity in promoting apoptotic pathways and other molecular pathways involved in breast cancer. Research indicates that phytochemicals have many beneficial effects, including anti-inflammatory, antioxidant, and antiproliferative effects. Phytochemicals have the potential to affect crucial signaling pathways of Breast cancer. Promiscuous phytochemicals such as curcumin, resveratrol, apigenin, and epigallocatechin gallate (EGCG), among others, have demonstrated notable anti-cancer effects in preclinical studies. This review delves deep into the therapeutic action and mechanism of various phytochemicals against breast cancer. It highlights the promiscuous role of multiple phytochemicals, their sources, and their target molecules in breast cancer, along with shedding light on some of the limitations of these phytochemicals. It discusses the key role of phytochemicals like Apigenin and Silibinin in combating the progression of Breast cancer and also emerging as crucial avenues to counter chemotherapeutic resistance. Effective treatments and cures should be developed to reduce the burden of non-communicable diseases and ensure human well-being and a good quality of life in order to accomplish sustainable development goals.
... In addition to their considerable health risks, they impose substantial psychological and economic burdens on families globally [1]. Despite notable advancements in medical science and technology, the cancer-associated mortality remains unavoidable and even high [2]. Therefore, the pursuit of effective therapeutic strategies for cancer therapy remains of great importance. ...
Despite their unique advantages and vast potential, nanomaterials employed in cancer therapy still encounter challenges such as uneven biodistribution, unintended drug leakage, and especially potential tissue damage caused by off-target toxicity. Bioinert nanomaterials, known for their excellent chemical stability, and minimal biological reactivity, can exert localized tumoricidal effects in response to specific external stimuli. However, the lack of precise control or poor penetration depth largely limits the therapeutic efficacy, necessitating the development of innovative stimuli-responsive therapeutic strategies. This study presents an alternative drug-responsive cancer therapeutic approach based on nickel-iron layered double hydroxide (NiFe-LDH), which exhibited negligible toxicity to both normal cells and cancer cells. By conjugating a platelet-derived growth factor receptor (PDGFR)-β-targeting cyclic peptide, NiFe-LDH achieved high specificity for prostate cancer cells, significantly enhancing tumor targeting and accumulation. Upon administration of deferoxamine mesylate (DFOM), an FDA-approved iron chelator, NiFe-LDH transitioned from a “bioinert” state to a “bioactive” nanotherapeutic through structural disassembly and robust release of nickel ions (Ni²⁺). The released ions disrupted mitochondrial function, upregulated insulin-like growth factor binding protein 3 (IGFBP3), and further inhibited the PI3K/AKT/mTOR signaling pathway, consequently leading to potent and selective induction of apoptosis in prostate cancer cells. Unlike conventional therapies, which often cause varying degrees of toxicity in non-target organs, this stimuli-responsive nanoplatform could minimize off-target effects and systemic toxicity by combining the non-toxic LDH with the clinically used DFOM. Our findings demonstrate that DFOM-responsive NiFe-LDH can effectively inhibit tumor growth in both cultured cells and tumor xenografts, suggesting a rational and clinically translatable platform for precision cancer therapy.
Graphical Abstract
... Globally, there are approximately 660,000 new cases of cervical cancer each year and 348,000 deaths, and more than 90% of these cases and deaths occur in low-and middle-income countries (LMICs) [2]. While cervical cancer incidence is declining in many countries [3] and cervical cancer is one of the only cancers with demonstrated improvements in premature mortality globally [4], these gains are largely concentrated in high-income countries, where women have better access to highly effective primary and secondary prevention strategies [2,5,6], Women in LMICs are therefore not seeing corresponding improvements in cervical cancer outcomes [3,7,8]. These access barriers to primary and secondary prevention strategies in LMICs are due to myriad factors from individual to societal levels [9,10]. ...
Background
Cervical cancer screening is an essential public health intervention, and critical to meeting the Global Strategy for Cervical Cancer Elimination goals – yet most women in low- and middle-income countries are never screened. There is a need to understand context-specific factors that facilitate or prevent women from engaging in screening.
Methods
This analysis leverages data collected in 2022–2023 from a national mobile phone-based survey in Kenya and from a household survey conducted in three districts of Malawi. Informed by the Health Belief Model, we assess whether women’s reported cervical cancer screening history (ever or never screened) was associated with their perceived susceptibility (awareness of cervical cancer risk factors), perceived severity (knowing someone who was affected by cervical cancer), perceived barriers (access to services), perceived benefits (trust in information about cervical cancer prevention), self-efficacy (engagement in other preventive health behaviors), and cues to action (speaking with others about cervical cancer prevention).
Results
Ever-screening for cervical cancer was reported by 49.7% of the 736 Kenyan respondents and 42.5% of the 261 Malawian respondents. There were few associations between women’s demographic or socioeconomic characteristics and screening history. The strongest associations were seen for cues to action (women who had spoken about cervical cancer with health workers had 1.88 the adjusted risk ratio for screening in Kenya [95% CI 1.59, 2.24] and 1.89 the adjusted risk in Malawi [95% CI 1.41, 2.54] compared to women who never had these conversations); and for knowing someone who had, or who had died due to, cervical cancer (aRR 1.34 and 1.30 respectively in Kenya, and aRR 2.03 and 1.46 respectively in Malawi). In both countries, self-efficacy was also associated with screening, as was perceived severity in both countries (i.e., knowing someone who had, or who had died due to cervical cancer, which was reported by many Kenyan and Malawian respondents). In Kenya, knowledge of cervical cancer risk factors was also associated with women’s screening history, as was access to other preventive health services in Malawi.
Conclusions
These results suggest promising areas for interventions aiming to increase cervical cancer screening in these contexts: encouraging health workers to discuss screening with eligible women, leveraging women’s peers who have been affected by cervical cancer, and promoting screening during other preventive health services.
... Esta doença é uma das principais causas de morte prematura globalmente, impactando diretamente a saúde pública (Murthy et al., 2024). A taxa de incidência e mortalidade associadas ao câncer tem aumentado em muitos países, especialmente devido ao envelhecimento da população e alterações nos padrões de risco, que estão ligados ao desenvolvimento socioeconômico (Santos et al., 2023). ...
... Consequently, evidence-based guidelines tailored to older patients have been notably lacking, potentially resulting in both undertreatment and overtreatment (8). This burden directly impacts the achievement of the United Nations Sustainable Development Goal 3.4 (SDG 3.4), which aims to reduce premature mortality through prevention and treatment of non-communicable diseases (9). ...
Background
Laryngeal cancer poses a significant health burden among older adults, with varying incidence, mortality, and disability-adjusted life years (DALYs) across regions. These disparities highlight the need for targeted interventions and tailored healthcare policies.
Objectives
To analyze global, regional, and national trends in laryngeal cancer incidence, mortality, and DALYs among older adults from 1990 to 2021 using age-period-cohort modeling and to assess the impact of demographic factors on disease burden across socio-developmental index (SDI) regions.
Materials and methods
Using the 2021 Global Burden of Diseases (GBD) database, trends in age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALYs rates (ASDR) were analyzed, with a focus on the impact of population growth and aging across SDI regions. Age-period-cohort and Joinpoint regression analyses were conducted to identify temporal trends and critical inflection points across SDI quintiles.
Results
From 1990 to 2021, the global ASIR of laryngeal cancer among older adults decreased from 15.16 to 12.25 per 100,000, with significant shifts in trends observed in 1995, 2002, and 2007. The disease burden in lowand middle SDI regions has declined relatively slower compared to high SDI regions, primarily driven by population growth.
Conclusions and significance
Laryngeal cancer trends highlight the need for targeted healthcare interventions. Low and middle SDI areas require improved access to care and prevention strategies, while high SDI regions benefit from personalized, geriatric-focused care.
... Colorectal cancer (CRC) is a common digestive tract tumor worldwide and one of the main causes of cancer-related death [1,2]. The antitumor function of the immune system plays a necessary role in regulating cancer progression [3]. ...
Background
Colorectal cancer (CRC) is the most common digestive cancer in the world. Microsatellite stability (MSS) and microsatellite instability (MSI-high) are important molecular subtypes of CRC closely related to tumor occurrence and progression and immunotherapy efficacy. The presence of CD8⁺ CXCR5⁺ follicular cytotoxic T (TFC) cells is strongly associated with autoimmune disease and CD8⁺ effector function. However, the roles of TFC cells in MSI-high CRC and MSS CRC are unclear. Here, we aimed to explore the characteristics of TFC cells in CRC and compare their biological functions between MSI-high and MSS CRC.
Methods
We explored the expression of TFC cell in tumor tissues and peripheral blood in our clinical cohort and public datasets. By combining single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing, we explored the potential function of TFC cells and developed a prediction model for CRC. We also compared the biological functions of these cells between MSS and MSI-high CRC and used flow cytometry and coculture experiments to explore their potential regulatory functions.
Results
TFC cell markers are downregulated in tumor tissues and patient peripheral blood vs. controls. The prediction model for CRC performed well in the training and validation cohorts (KM plot p < 0.001). MSS CRC patients exhibit enrichment of genes related to the cell cycle (MKI67) and T cell activation (CD38 and HLA-DR) and decreased enrichment of immune checkpoint markers (PD1, TIM3, and LAG3). The expression of TFC cell-related genes is positively correlated with that of CD8⁺IFN-γ⁺-related genes and closely related to that of TLS-related genes in MSS CRC. The proportion of TFC cells is positively correlated with that of CD19⁺CD38⁺ B cells in MSS CRC.
Conclusions
The prognostic prediction model has good predictive value. In MSS CRC, TFC cells function mostly in T cell activation and the cell cycle and have low expression of immune checkpoint molecules, which may influence the effectiveness of ICB therapy. TFC cells may regulate antitumor function by regulating CD19⁺ CD38⁺ B cells and TLSs.
... [3] , 旨在到2030年将包括癌症在内的4 种主要非传染性疾病的过早死亡率降低三分之一, 并且在 2017年世界卫生大会通过的第70.12号决议 [4] [11] , 终生患癌风险指标提供了一个更为精确的癌症 负担评估工具. 这种评估方式不仅能够适应不同国家的人口 ...
... Cancer is one of the most significant global health challenges and is a leading cause of death worldwide, accounting for one in six deaths globally (16.8%) [1,2]. Predictions indicate that by 2040 the number of new cancer cases is likely to exceed 30 million [3]. Glioblastoma multiforme (GBM), identified as a grade IV astrocytoma, is the predominant, aggressive, and fatal primary brain tumor among adults [4]. ...
In this study, we hypothesized that biotinylated and/or glycidol-flanked fourth-generation polyamidoamine (PAMAM G4) dendrimers could be a tool for efficient drug transport into glioma and liver cancer cells. For this purpose, native PAMAM (G4) dendrimers, biotinylated (G4B), glycidylated (G4gl), and biotinylated and glycidylated (G4Bgl), were synthesized, and their cytotoxicity, uptake, and accumulation in vitro and in vivo were studied in relation to the transport mediated by the sodium-dependent multivitamin transporter (SMVT). The studies showed that the human temozolomide-resistant glioma cell line (U-118 MG) and hepatocellular carcinoma cell line (HepG2) indicated a higher amount of SMVT than human HaCaT keratinocytes (HaCaTs) used as a model of normal cells. The G4gl and G4Bgl dendrimers were highly biocompatible in vitro (they did not affect proliferation and mitochondrial activity) against HaCaT and U-118 MG glioma cells and in vivo (against Caenorhabditis elegans and Wistar rats). The studied compounds penetrated efficiently into all studied cell lines, but inconsistently with the uptake pattern observed for biotin and disproportionately for the level of SMVT. G4Bgl was taken up and accumulated after 48 h to the highest degree in glioma U-118 MG cells, where it was distributed in the whole cell area, including the nuclei. It did not induce resistance symptoms in glioma cells, unlike HepG2 cells. Based on studies on Wistar rats, there are indications that it can also penetrate the blood–brain barrier and act in the central nervous system area. Therefore, it might be a promising candidate for a carrier of therapeutic agents in glioma therapy. In turn, visualization with a confocal microscope showed that biotinylated G4B penetrated efficiently into the body of C. elegans, and it may be a useful vehicle for drugs used in anthelmintic therapy.
... High-income countries see greater reductions, especially in cancers with early detection strategies like breast and colorectal cancer, compared to low-income countries. Cervical cancer, with effective prevention programs, shows significant declines in both high-and low-income countries [52]. Additionally, the Health of the Nation Report 2024 by Apollo Hospital Group predicts a doubling of colon cancer cases in individuals under 50 in the next decade [53]. ...
Cancer, a pervasive and multifaceted disease, has afflicted humanity since ancient times, as evidenced by early references in the Edwin Smith Papyrus and the Ebers Papyrus. Over centuries, our understanding and treatment of cancer have evolved significantly, transitioning from rudimentary remedies to advanced modalities like chemotherapy, radiation therapy, and precision medicine. Despite these advancements, cancer remains a major global health challenge. As of 2022, nearly 20 million new cancer cases and 10 million cancer-related deaths were reported worldwide. In India, the situation is particularly dire, with over 1.41 million new cases and more than 916,827 deaths in 2022, exacerbated by socioeconomic disparities, cultural stigmas, and healthcare barriers. This review traces the historical evolution of cancer treatment from ancient civilizations to modern times, highlighting key medical milestones and breakthroughs. It examines the global and Indian cancer burden, emphasizing the critical barriers to early diagnosis and effective treatment. These barriers include health system deficiencies, socioeconomic challenges, delayed diagnosis, low health literacy, and inadequate screening programs. The review was conducted through a comprehensive literature search using databases such as PubMed, Google Scholar, Journal Storage (JSTOR), and various other sources focusing on historical texts, epidemiological studies, and current medical research. The search aimed to gather a broad spectrum of perspectives and evidence to provide a well-rounded understanding of cancer's historical journey and current landscape.
Colon adenocarcinoma (COAD) is the most common subtype of colorectal cancer, originating from glandular cells in the colon. Despite diagnostic and therapeutic advances, its prognosis remains poor. Copper, an essential micronutrient, is involved in tumorigenesis and other biological processes. In this study, we identified copper metabolism‐related genes (CMRG) associated with COAD prognosis from TCGA and GEO databases and constructed a CMRG‐based risk model. We assessed its clinical relevance through analyses of immune infiltration, immunotherapy response, and drug sensitivity. Single‐cell sequencing revealed the spatial and cellular distribution of CMRG in COAD tissues, providing insight into their roles in the tumour microenvironment. COX19 was selected for further validation, and in vitro experiments (western blot, PCR, siRNA, colony formation, and Transwell assays) confirmed its role in promoting COAD cell invasion and proliferation. These findings highlight the involvement of copper metabolism in COAD progression and suggest potential targets for therapy.
The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus (EBV), the first virus confirmed to cause human cancer. Viral infections significantly contribute to the global cancer burden, with seven known Group 1 oncogenic viruses, including hepatitis B virus (HBV), human papillomavirus (HPV), EBV, Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), and human immunodeficiency virus (HIV). These oncogenic viruses induce cellular transformation and cancer development by altering various biological processes within host cells, particularly under immunosuppression or co-carcinogenic exposures. These viruses are primarily associated with hepatocellular carcinoma, gastric cancer, cervical cancer, nasopharyngeal carcinoma, Kaposi sarcoma, lymphoma, and adult T-cell leukemia/lymphoma. Understanding the mechanisms of viral oncogenesis is crucial for identifying and characterizing the early biological processes of virus-related cancers, providing new targets and strategies for treatment or prevention. This review first outlines the global epidemiology of virus-related tumors, milestone events in research, and the process by which oncogenic viruses infect target cells. It then focuses on the molecular mechanisms by which these viruses induce tumors directly or indirectly, including the regulation of oncogenes or tumor suppressor genes, induction of genomic instability, disruption of regular life cycle of cells, immune suppression, chronic inflammation, and inducing angiogenesis. Finally, current therapeutic strategies for virus-related tumors and recent advances in preclinical and clinical research are discussed.
Introduction
MicroRNAs (miRNAs) regulate gene expression and play an important role in carcinogenesis through complex interactions with messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Despite their established influence on tumor progression and therapeutic resistance, the application of miRNA interaction networks for tumor tissue-of-origin (TOO) classification remains underexplored.
Methods
We developed a machine learning (ML) framework that integrates miRNA-mRNA-lncRNA interaction networks to classify tumors by their tissue of origin. Using transcriptomic profiles from 14 cancer types in The Cancer Genome Atlas (TCGA), we constructed co-expression networks and applied multiple feature selection techniques including recursive feature elimination (RFE), random forest (RF), Boruta, and linear discriminant analysis (LDA) to identify a minimal yet informative subset of miRNA features. Ensemble ML algorithms were trained and validated with stratified five-fold cross-validation for robust performance assessment across class distributions.
Results
Our models achieved an overall 99% classification accuracy, distinguishing 14 cancer types with high robustness and generalizability. A minimal set of 150 miRNAs selected via RFE resulted in optimal performance across all classifiers. Furthermore, in silico validation revealed that many of the top miRNAs, including miR-21-5p, miR-93-5p, and miR-10b-5p , were not only highly central in the network but also correlated with patient survival and drug response. In addition, functional enrichment analyses indicated significant involvement of miRNAs in pathways such as TGF -beta signaling, epithelial-mesenchymal transition, and immune modulation. Our comparative analysis demonstrated that models based on miRNA outperformed those using mRNA or lncRNA classifiers.
Discussion
Our integrated framework provides a biologically grounded, interpretable, and highly accurate approach for tumor tissue-of-origin classification. The identified miRNA biomarkers demonstrate strong translational potential, supported by clinical trial overlap, drug sensitivity data, and survival analyses. This work highlights the power of combining miRNA network biology with ML to improve precision oncology diagnostics and supports future development of liquid biopsy-based cancer classification.
Cancer remains a significant global health challenge, with its progression driven by both genetic mutations and reversible epigenetic modifications. This review highlights the potential of phytochemicals to modulate epigenetic mechanisms for cancer prevention and treatment. Natural compounds such as quercetin, EGCG, genistein, and β‐elemene interact with key processes such as DNA methylation, histone modifications, and non‐coding RNA regulation. These mechanisms enable the reactivation of tumor suppressor genes, increased sensitivity to conventional therapy and mitigation of drug resistance. For instance, EGCG improves the efficacy of cisplatin by altering DNA methylation patterns, while genistein influences breast cancer progression through HER2 pathway regulation. However, challenges such as low bioavailability, variability in compound composition, and the need for robust clinical validation remain. Further high‐quality clinical trials are required to confirm the efficacy and safety of these compounds in cancer prevention and therapy.
Current early cancer diagnostic technologies, such as imaging, molecular tests, endoscopic techniques, and biopsies, face considerable challenges in low‐and middle‐income countries (LMICs) due to high costs, procedural complexity, and limited resource access. Microneedle‐based liquid biopsy for skin interstitial fluid (ISF) offers a practical and minimally invasive alternative for cancer diagnosis in these settings. This review systematically examines ISF liquid biopsy methods for their effectiveness in capturing cancer biomarkers directly from the skin and assesses their potential to address diagnostic needs in low‐resource environments. Recent innovations in microneedle design and ISF underscore their potential in enabling early, accessible cancer detection tailored to LMICs' needs. Additionally, integrating artificial intelligence (AI) for data interpretation is proposed as a way to enhance diagnostic accuracy and enable real‐time point‐of‐care (POC) applications. Collectively, these advances illustrate a flexible, scalable model for accessible cancer diagnostics, with significant implications for improving early detection and healthcare quality in resource‐limited environments.
As a new chemical class of bis-diterpene heterodimers, spiroamentotaxols A–D (1–4) are characterized by a complex 6/6/6/5/6/6/6/6 spiro-octacyclic ring system, which is likely biogenetically derived from a Diels–Alder [4 + 2] cycloaddition between an ent-kaurene and a C20-norabietane. The spiroamentotaxols possess a distinctive spiro[bicyclo[3.2.1]octane-7,2′-bicyclo[2.2.2]octene] motif. Through the application of molecular ion networking (MoIN), these intermolecular Diels–Alder isomers were isolated from the renewable twigs and needles of the endangered Chinese conifer Amentotaxus yunnanensis. Their chemical structures were elucidated using spectroscopic methods, electronic circular dichroism calculations, and X-ray diffraction analysis. From a structural diversity perspective, two semi-synthetic analogs, namely, 7′-deoxy-6′-en-spiroamentotaxol A (1a) and 7′-deoxy-spiroamentotaxol A (1b), were synthesized from the relatively major compound 1. These spiro-polycyclic compounds were evaluated for their in vitro anti-inflammatory and anticancer activities. In particular, compound 1 attenuated inflammation in both RAW 264.7 macrophage and BV2 microglial cells at a non-toxic concentration of 20 μM, with the lipopolysaccharide (LPS)-induced nitric oxide production inhibition rates of 46.66% and 32.37%, respectively. 1b exhibited efficacy against a panel of human cancer cell lines (A549, MCF7, HCT116, RKO, and HepG2), with IC50 values ranging from 6.27 to 14.10 μM. In the case of HCT116 cells, 1b specifically influenced cell-cycle progression at the G2 phase and induced apoptosis. The findings highlight the importance of conserving plant species diversity as a means to sustain chemical diversity and serve as a potential source of new therapeutic agents for cancer treatment.
Triple‐negative breast cancer (TNBC) represents a highly aggressive and prognostically unfavorable subtype of breast cancer, characterized by the absence of common hormone receptors, which renders conventional therapies largely ineffective. This review comprehensively examines the molecular and clinical characteristics of TNBC, underscoring the substantial challenges inherent in its treatment and the innovative potential of targeted nanoprobes in advancing both diagnostic and therapeutic paradigms. Through the modification of targeting molecules, nanoprobes can deliver therapeutic agents highly specific to TNBC cells, thus significantly improving the sensitivity of diagnostic modalities and the efficacy of therapeutic interventions. Our discussion systematically explores the application of various targeting molecules and their advantages and limitations. In addition, this review presents a series of multifunctional targeted nanoprobes that are designed to perform both diagnostic and therapeutic functions, thus providing a synergistic approach to the treatment of TNBC. These advanced nanoprobes enable precise tumor localization while monitoring the therapeutic response in real time, thus facilitating a more personalized and dynamic treatment regimen. The major obstacles encountered during clinical translation are discussed in detail. The use of targeted nanoprobes represents a major leap forward in personalized medicine for TNBC, and current research efforts will continue to refine these technologies to improve clinical applicability.
Breast cancer remains the leading cause of death among women globally, with an increasing incidence. Although
numerous FDA-approved treatments are available, issues such as drug resistance and selectivity necessitate the
development of more effective agents with fewer side effects. In this study, we synthesized a series of indole
derivatives containing triazole or oxadiazole rings with anti-tumor activity. The structures of all synthesized
compounds were confirmed through infrared (IR) spectroscopy, proton nuclear magnetic resonance (
carbon-13 nuclear magnetic resonance (
13
1
HNMR),
CNMR), and mass spectrometry. These compounds were assessed for
their potential anticancer activity against MCF-7 breast carcinoma cells using the MTT assay. The results indi
cated that the indole derivatives exhibited antitumor activity, with IC50 values ranging from 44.1 to 93.2 µg/ml.
Five compounds, specifically 2, 3, 4a, 4c, and 4d, were further evaluated through in-silico studies. Their in
teractions with the receptor protein CDK4 (PDB ID: 2W96) were analyzed to determine their potential as anti-
breast cancer agents. Effective binding was observed between these compounds and the receptor. Molecular
docking studies revealed that compounds 4a and 4d showed the highest activity, with binding scores of -8.36 and -8.18 kcal/mol, respectively. Notably, compound 4a demonstrated a stronger binding affinity than compound 4d
during dynamic simulations. The ADMET study indicated that all compounds are highly safe for biological use.
According to the BOILED-Egg model, compounds 4a, 4b, 4c, and 4d are unable to cross the blood-brain barrier,
suggesting minimal impact on the central nervous system while still being able to traverse other biological
membranes.
Background
Rising cancer incidence, particularly for colorectal cancer, has been reported in young adults. This study examined whether this is related to an increase in mortality.
Methods
We analysed World Health Organization (WHO) mortality data among young adults aged 25-49 in 15 most populous upper-middle and high-income countries from 1990 to 2021 with reliable data. Mid-year populations were retrieved from the United Nations for the American Countries and from the WHO for the other countries. We compared age-standardised mortality rates (ASMRs) in 2019-2021 to 2009-2011 and performed joinpoint regression analysis for all cancers and selected most common cancer sites: colorectum, pancreas, lung and breast.
Results
In 2019-2021, the highest ASMRs (per 100,000) were in Romanian males (38.6) and Argentinian females (45.9), while the lowest ones in Japan (males: 16.3; females: 22.7). ASMRs for colorectal cancers increased in 2019-2021 compared to 2009-2011 in nine countries among men and in seven countries among women. The highest increases were in the UK (males: +26.1%; females: +33.7%), Canada (males: +25.3%), and Mexico (males: +33.5%; females: +29.7%). Long-term analysis over the last three decades showed declining trends in total cancer mortality in the majority of countries, in lung cancer mortality across all countries, and in breast cancer in all countries except in Latin America.
Conclusions
While mortality from common cancers has generally decreased over the past three decades, mortality from colorectal cancer has increased in some countries. This highlights the need to control the obesity epidemic and implement targeted surveillance strategies in young populations.
This article presents global cancer statistics by world region for the year 2022 based on updated estimates from the International Agency for Research on Cancer (IARC). There were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer (including NMSC). The estimates suggest that approximately one in five men or women develop cancer in a lifetime, whereas around one in nine men and one in 12 women die from it. Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases, or one in eight cancers worldwide (12.4% of all cancers globally), followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer was also the leading cause of cancer death, with an estimated 1.8 million deaths (18.7%), followed by colorectal (9.3%), liver (7.8%), female breast (6.9%), and stomach (6.8%) cancers. Breast cancer and lung cancer were the most frequent cancers in women and men, respectively (both cases and deaths). Incidence rates (including NMSC) varied from four‐fold to five‐fold across world regions, from over 500 in Australia/New Zealand (507.9 per 100,000) to under 100 in Western Africa (97.1 per 100,000) among men, and from over 400 in Australia/New Zealand (410.5 per 100,000) to close to 100 in South‐Central Asia (103.3 per 100,000) among women. The authors examine the geographic variability across 20 world regions for the 10 leading cancer types, discussing recent trends, the underlying determinants, and the prospects for global cancer prevention and control. With demographics‐based predictions indicating that the number of new cases of cancer will reach 35 million by 2050, investments in prevention, including the targeting of key risk factors for cancer (including smoking, overweight and obesity, and infection), could avert millions of future cancer diagnoses and save many lives worldwide, bringing huge economic as well as societal dividends to countries over the forthcoming decades.
Background:
Leukemia is a common malignancy that has four main subtypes and is a threat to human health. Understanding the epidemiological status of leukemia and its four main subtypes globally is important for allocating appropriate resources, guiding clinical practice, and furthering scientific research.
Methods:
Average annual percentage changes (AAPCs) were calculated to estimate the change trends of age-standardized rates (ASRs) from 1990 to 2019 in 204 countries and territories. The risk factors for leukemia death and disability-adjusted life-year (DALY) were also analyzed. In addition, the future trends in ASRs were projected through 2030.
Results:
The total number of incident cases, deaths, and DALYs from leukemia in 2019 was 0.64, 0.33, and 11.66 million, respectively. Decreasing trends in age-standardized incidence rate (ASIR), the age-standardized death rate (ASDR), and age-standardized DALY rate were detected on a global level while increasing trends in ASIR were detected in the high-sociodemographic index (SDI) regions. The leukemia burden was heavier in males than in females. By cause, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL) were more likely to impose a burden on the elderly, while acute lymphoblastic leukemia (ALL) showed a greater impact in the younger population. A significant positive correlation was observed between SDI and AAPC in ASIR, while SDI was negatively correlated with AAPCs in both ASDR and age-standardized DALY rate. Smoking remained the most significant risk factor associated with leukemia-related death and DALY, especially in males. Similar deaths and DALYs were caused by smoking and high body mass index (BMI) in females. Future projections through 2030 estimated that ASIR and ASDR will continue to increase, while the DALY rate is predicted to decline.
Conclusions:
Patterns and trends of leukemia burden are correlated with SDI. The estimated contributions to leukemia deaths indicate that timely measures are needed to reduce smoking and obesity.
Background
Colorectal cancer is the third leading cause of cancer deaths worldwide. Given the recent increasing trends in colorectal cancer incidence globally, up-to-date information on the colorectal cancer burden could guide screening, early detection, and treatment strategies, and help effectively allocate resources. We examined the temporal patterns of the global, regional, and national burden of colorectal cancer and its risk factors in 204 countries and territories across the past three decades.
Methods
Estimates of incidence, mortality, and disability-adjusted life years (DALYs) for colorectal cancer were generated as a part of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 by age, sex, and geographical location for the period 1990–2019. Mortality estimates were produced using the cause of death ensemble model. We also calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer.
Findings
Globally, between 1990 and 2019, colorectal cancer incident cases more than doubled, from 842 098 (95% uncertainty interval [UI] 810 408–868 574) to 2·17 million (2·00–2·34), and deaths increased from 518 126 (493 682–537 877) to 1·09 million (1·02–1·15). The global age-standardised incidence rate increased from 22·2 (95% UI 21·3–23·0) per 100 000 to 26·7 (24·6–28·9) per 100 000, whereas the age-standardised mortality rate decreased from 14·3 (13·5–14·9) per 100 000 to 13·7 (12·6–14·5) per 100 000 and the age-standardised DALY rate decreased from 308·5 (294·7–320·7) per 100 000 to 295·5 (275·2–313·0) per 100 000 from 1990 through 2019. Taiwan (province of China; 62·0 [48·9–80·0] per 100 000), Monaco (60·7 [48·5–73·6] per 100 000), and Andorra (56·6 [42·8–71·9] per 100 000) had the highest age-standardised incidence rates, while Greenland (31·4 [26·0–37·1] per 100 000), Brunei (30·3 [26·6–34·1] per 100 000), and Hungary (28·6 [23·6–34·0] per 100 000) had the highest age-standardised mortality rates. From 1990 through 2019, a substantial rise in incidence rates was observed in younger adults (age <50 years), particularly in high Socio-demographic Index (SDI) countries. Globally, a diet low in milk (15·6%), smoking (13·3%), a diet low in calcium (12·9%), and alcohol use (9·9%) were the main contributors to colorectal cancer DALYs in 2019.
Interpretation
The increase in incidence rates in people younger than 50 years requires vigilance from researchers, clinicians, and policy makers and a possible reconsideration of screening guidelines. The fast-rising burden in low SDI and middle SDI countries in Asia and Africa calls for colorectal cancer prevention approaches, greater awareness, and cost-effective screening and therapeutic options in these regions.
Funding
Bill & Melinda Gates Foundation.
Heavy alcohol consumption in mid-adulthood is an established risk factor of colorectal cancer (CRC). Alcohol use in early adulthood is common, but its association with subsequent CRC risk remains largely unknown. We prospectively investigated the association of average alcohol intake in early adulthood (age 18–22) with CRC risk later in life among 191,543 participants of the Nurses’ Health Study ([NHS], 1988–2014), NHSII (1989–2015) and Health Professionals Follow-Up Study (1988–2014). Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), which were pooled using random effects models. We documented 2,624 CRC cases. High alcohol consumption in early adulthood (≥ 15 g/day) was associated with a higher CRC risk (multivariable HR 1.28, 95% CI 0.99–1.66, Ptrend = 0.02; Pheterogeneity = 0.44), after adjusting for potential confounding factors in early adulthood. Among never/light smokers in early adulthood, the risk associated with high alcohol consumption in early adulthood was elevated (HR 1.53, 95% CI 1.04–2.24), compared with those who had < 1 g/day of alcohol intake. The suggestive higher CRC risk associated with high alcohol consumption in early adulthood was similar in those who had < 15 g/day (HR 1.35, 95% CI 0.98–1.86) versus ≥ 15 g/day of midlife alcohol intake (HR 1.35, 95% CI 0.89–2.05), compared with nondrinkers in both life stages. The findings from these large prospective cohort studies suggest that higher alcohol intake in early adulthood may be associated with a higher risk of developing CRC later in life.
Prostate cancer is a complex disease that affects millions of men globally, predominantly in high human development index regions. Patients with localized disease at a low to intermediate risk of recurrence generally have a favourable outcome of 99% overall survival for 10 years if the disease is detected and treated at an early stage. Key genetic alterations include fusions of TMPRSS2 with ETS family genes, amplification of the MYC oncogene, deletion and/or mutation of PTEN and TP53 and, in advanced disease, amplification and/or mutation of the androgen receptor (AR). Prostate cancer is usually diagnosed by prostate biopsy prompted by a blood test to measure prostate-specific antigen levels and/or digital rectal examination. Treatment for localized disease includes active surveillance, radical prostatectomy or ablative radiotherapy as curative approaches. Men whose disease relapses after prostatectomy are treated with salvage radiotherapy and/or androgen deprivation therapy (ADT) for local relapse, or with ADT combined with chemotherapy or novel androgen signalling-targeted agents for systemic relapse. Advanced prostate cancer often progresses despite androgen ablation and is then considered castration-resistant and incurable. Current treatment options include AR-targeted agents, chemotherapy, radionuclides and the poly(ADP-ribose) inhibitor olaparib. Current research aims to improve prostate cancer detection, management and outcomes, including understanding the fundamental biology at all stages of the disease.
Background:
WHO is developing a global strategy towards eliminating cervical cancer as a public health problem, which proposes an elimination threshold of four cases per 100 000 women and includes 2030 triple-intervention coverage targets for scale-up of human papillomavirus (HPV) vaccination to 90%, twice-lifetime cervical screening to 70%, and treatment of pre-invasive lesions and invasive cancer to 90%. We assessed the impact of achieving the 90-70-90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century. We also assessed the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals (SDGs)-a one-third reduction in premature mortality from non-communicable diseases by 2030.
Methods:
The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC) involves three independent, dynamic models of HPV infection, cervical carcinogenesis, screening, and precancer and invasive cancer treatment. Reductions in age-standardised rates of cervical cancer mortality in 78 low-income and lower-middle-income countries (LMICs) were estimated for three core scenarios: girls-only vaccination at age 9 years with catch-up for girls aged 10-14 years; girls-only vaccination plus once-lifetime screening and cancer treatment scale-up; and girls-only vaccination plus twice-lifetime screening and cancer treatment scale-up. Vaccination was assumed to provide 100% lifetime protection against infections with HPV types 16, 18, 31, 33, 45, 52, and 58, and to scale up to 90% coverage in 2020. Cervical screening involved HPV testing at age 35 years, or at ages 35 years and 45 years, with scale-up to 45% coverage by 2023, 70% by 2030, and 90% by 2045, and we assumed that 50% of women with invasive cervical cancer would receive appropriate surgery, radiotherapy, and chemotherapy by 2023, which would increase to 90% by 2030. We summarised results using the median (range) of model predictions.
Findings:
In 2020, the estimated cervical cancer mortality rate across all 78 LMICs was 13·2 (range 12·9-14·1) per 100 000 women. Compared to the status quo, by 2030, vaccination alone would have minimal impact on cervical cancer mortality, leading to a 0·1% (0·1-0·5) reduction, but additionally scaling up twice-lifetime screening and cancer treatment would reduce mortality by 34·2% (23·3-37·8), averting 300 000 (300 000-400 000) deaths by 2030 (with similar results for once-lifetime screening). By 2070, scaling up vaccination alone would reduce mortality by 61·7% (61·4-66·1), averting 4·8 million (4·1-4·8) deaths. By 2070, additionally scaling up screening and cancer treatment would reduce mortality by 88·9% (84·0-89·3), averting 13·3 million (13·1-13·6) deaths (with once-lifetime screening), or by 92·3% (88·4-93·0), averting 14·6 million (14·1-14·6) deaths (with twice-lifetime screening). By 2120, vaccination alone would reduce mortality by 89·5% (86·6-89·9), averting 45·8 million (44·7-46·4) deaths. By 2120, additionally scaling up screening and cancer treatment would reduce mortality by 97·9% (95·0-98·0), averting 60·8 million (60·2-61·2) deaths (with once-lifetime screening), or by 98·6% (96·5-98·6), averting 62·6 million (62·1-62·8) deaths (with twice-lifetime screening). With the WHO triple-intervention strategy, over the next 10 years, about half (48% [45-55]) of deaths averted would be in sub-Saharan Africa and almost a third (32% [29-34]) would be in South Asia; over the next 100 years, almost 90% of deaths averted would be in these regions. For premature deaths (age 30-69 years), the WHO triple-intervention strategy would result in rate reductions of 33·9% (24·4-37·9) by 2030, 96·2% (94·3-96·8) by 2070, and 98·6% (96·9-98·8) by 2120.
Interpretation:
These findings emphasise the importance of acting immediately on three fronts to scale up vaccination, screening, and treatment for pre-invasive and invasive cervical cancer. In the next 10 years, a one-third reduction in the rate of premature mortality from cervical cancer in LMICs is possible, contributing to the realisation of the 2030 UN SDGs. Over the next century, successful implementation of the WHO elimination strategy would reduce cervical cancer mortality by almost 99% and save more than 62 million women's lives.
Funding:
WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Germany Federal Ministry of Health, National Health and Medical Research Council Australia, Centre for Research Excellence in Cervical Cancer Control, Canadian Institute of Health Research, Compute Canada, and Fonds de recherche du Québec-Santé.
Background
The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality.
Objective
To determine whether PSA screening decreases PCa mortality for up to 16 yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended.
Design, setting, and participants
This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55–69 yr), selected from population registry.
Outcome measurements and statistical analysis
The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended.
Results and limitations
The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72–0.89, p < 0.001) at 16 yr. The difference in absolute PCa mortality increased from 0.14% at 13 yr to 0.18% at 16 yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16 yr compared with 742 at 13 yr. The number needed to diagnose was reduced to 18 from 26 at 13 yr. Men with PCa detected during the first round had a higher prevalence of PSA >20 ng/ml (9.9% compared with 4.1% in the second round, p < 0.001) and higher PCa mortality (hazard ratio = 1.86, p < 0.001) than those detected subsequently.
Conclusions
Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level.
Patient summary
In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer.
Gastric cancer remains one of the most common and deadly cancers worldwide, especially among older males. Based on GLOBOCAN 2018 data, stomach cancer is the 5th most common neoplasm and the 3rd most deadly cancer, with an estimated 783,000 deaths in 2018. Gastric cancer incidence and mortality are highly variable by region and highly dependent on diet and Helicobacter pylori infection. While strides in preventing and treating H. pylori infection have decreased the overall incidence of gastric cancer, they have also contributed to an increase in the incidence of cardia gastric cancer, a rare subtype of the neoplasm that has grown 7-fold in the past decades. A better understanding of the etiology and risk factors of the disease can help reach a consensus in approaching H. pylori infection. Dietary modification, smoking cessation, and exercise hold promise in preventing gastric cancer, while genetic testing is enabling earlier diagnosis and thus greater survival.
Background:
To curb the rising global burden of non-communicable diseases (NCDs), the UN Sustainable Development Goals (SDGs) include a target to reduce premature mortality from NCDs by a third by 2030. A quantitative assessment of the effect on longevity of meeting this target is one of the many important measures needed to advocate and inform national disease control policies. We did a global analysis to estimate improvements in average expected years lived between 30 and 70 years of age that would result from meeting the SDG target.
Methods:
We estimated age-specific mortality in 183 countries in 2015, for the four major NCDs (cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes) and all NCDs combined, using data from WHO Global Health Estimates. We then estimated the potential gains in average expected years lived between 30 and 70 years of age (LE[30-70)) by eliminating all or a third of premature mortality from specific causes of death in countries grouped by World Bank income groups. The feasibility of reducing mortality to the targeted level over 15 years was also assessed on the basis of historical mortality trends from 2000 to 2015.
Findings:
Reducing a third of premature mortality from NCDs over 15 years is feasible in high-income and upper-middle-income countries, but remains challenging in countries with lower income levels. National longevity will improve if this target is met, corresponding to an average gain in LE[30-70) of 0·64 years worldwide from reduced premature mortality for the four major NCDs and 0·80 years for all NCDs. According to major NCD type, the largest gains attributable to cardiovascular diseases would be in lower-middle-income countries (a gain of 0·45 years), whereas gains attributable to cancer would be in low-income countries (0·33 years).
Interpretation:
A one-third reduction in premature mortality from the major NCDs in 2015-30 would have substantial effects on longevity. High-level political commitments to effective and equitable national surveillance and prioritised prevention, early detection, and treatment programmes tailored to the major NCD types are needed urgently in lower-resourced settings if this SDG target is to be met by 2030.
Funding:
None.
Background & objectives:
Causative linkages of smokeless tobacco (SLT) use with oral potentially malignant disorders and cancers of oral cavity, oesophagus and pancreas have been reported. Published meta-analyses have provided pooled risk estimates for major cancers caused by SLT, both on global and regional levels. This systematic review was aimed at summarizing the available studies on occurrence and mortality risk of common cancers due to various SLT products.
Methods:
PubMed and Google Scholar databases were systematically searched from 1985 till January 2018 for observational studies on SLT and cancer. The included studies were evaluated and data were extracted and reviewed.
Results:
The review included 80 studies providing 121 risk estimates for various cancers. Majority of the studies from South-East Asian Region (SEAR) and Eastern Mediterranean Region (EMR) showed a significant positive association of SLT use with oral [odds ratio (OR) ranging from 1.48 to 27.4] and oesophageal cancers (OR between 2.06 and 12.8), while studies from European Region (EUR) reported a positive association with pancreatic cancer (OR between 1.6 and 2.1). Cancer-related mortality was evaluated in a few reports with higher risk of mortality for lung (OR between 2.0 and 9.1), cervical (OR 2.0) and prostate (OR 2.1) cancers. A wide variation was noted in the association of various cancers and specific SLT products based on their nature, methods of use and inherent toxicity. The majority of chewing tobacco products displayed higher risk for oral and oesophageal cancers while the same was not observed for snus.
Interpretation & conclusions:
This review emphasizes on the significantly positive association of SLT use with oral and oesophageal cancers in SEAR and EMR and pancreatic cancer in EUR. Mortality estimates for SLT-associated cancers need further analysis. Risk analysis for cancers of other sites in SLT users also requires multicentric well-designed studies.
The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial.
A total of 76 685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided.
Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P(interaction) = .81), pretrial PSA testing (P(interaction) = .52), and comorbidity (P(interaction) = .68).
After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.
Disparities in prostate cancer incidence and outcomes are a hallmark of the global pattern of prostate cancer, with men of African descent suffering disproportionately from this disease. The causes of these disparities are poorly understood.
A review of the literature was undertaken to evaluate the role that genetic susceptibility may play in prostate cancer etiology and outcomes, with a particular emphasis on disparities.
The genetic contribution to prostate cancer is well established, and a number of candidate prostate cancer genes have been identified. Significant differences in the frequency of risk alleles in these genes have been identified across the major races. These allele frequency differences may in part explain an increased susceptibility to prostate cancer in some populations. In addition, non-genetic factors contribute significantly to prostate cancer disparities, and the cumulative contribution of both genetic and non-genetic factors to poor-prognosis prostate cancer may explain the poorer outcomes experienced by men of African descent.
Prostate cancer disparities are a function of genetic susceptibility as well as environment, behavior, and health care factors acting in the context of this genetic susceptibility. Elimination of global prostate cancer disparities requires a full understanding of the effects of all of these factors on prostate cancer etiology and outcomes.
Chronic hepatitis C (HCV) infection is a major global public health threat and in 2019 there were an estimated 58 million infected globally and 290,000 deaths. Elimination of viral hepatitis B/C as a public health threat by 2030 is defined as a 90% incidence reduction and a 65% mortality reduction. The Western Pacific region is one of the most affected regions with 10 million people living with HCV, one-fifth of the global burden. We review progress towards HCV elimination in the Western Pacific region since 2015. Key developments in the region, which comprises of 37 high-and-middle-income countries, include the following: 20 countries have national hepatitis action plans, 19 have conducted recent disease burden and investment cases, 10 have scaled-up hepatitis services at primary health care level, and in 11 countries, domestic financing including social health insurance support DAA costs. We highlight six countries' experience in navigating the path towards HCV elimination: Cambodia, China, Malaysia, Mongolia, Philippines, and Viet Nam. Future initiatives to accelerate elimination are expanding access to community-based testing using HCV point-of-care tests among at-risk and general populations; adopting decentralized and integrated HCV one-stop services at harm reduction sites, detention settings and primary care; expanding treatment to include children and adolescents; address stigma and discrimination; and ensuring sustainable financing through domestic resources to scale-up testing, treatment and prevention. The COVID-19 pandemic has a significant impact on hepatitis response across the region on community and facility-based testing, treatment initiation, monitoring and cancer screening, which is projected to delay elimination goals.
One quarter of the global population is estimated to have nonalcoholic fatty liver disease (NAFLD). The incidence of nonalcoholic steatohepatitis (NASH) is projected to increase by up to 56% in the next 10 years. NAFLD is already the fastest growing cause of hepatocellular carcinoma (HCC) in the USA, France and the UK. Globally, the prevalence of NAFLD-related HCC is likely to increase concomitantly with the growing obesity epidemic. The estimated annual incidence of HCC ranges from 0.5% to 2.6% among patients with NASH cirrhosis. The incidence of HCC among patients with non-cirrhotic NAFLD is lower, approximately 0.1 to 1.3 per 1,000 patient-years. Although the incidence of NAFLD-related HCC is lower than that of HCC of other aetiologies such as hepatitis C, more people have NAFLD than other liver diseases. Urgent measures that increase global awareness and tackle the metabolic risk factors are necessary to reduce the impending burden of NAFLD-related HCC. Emerging evidence indicates that reduced immune surveillance, increased gut inflammation and gut dysbiosis are potential key steps in tumorigenesis. In this Review, we discuss the global epidemiology, projections and risk factors for NAFLD-related HCC, and propose preventive strategies to tackle this growing problem.
Objectives
To provide updated estimates of the global burden of oesophageal and gastric cancer by subsite and type.
Methods
Using data from population-based cancer registries, proportions of oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) out of all oesophageal as well as cardia gastric cancer (CGC) and non-CGC (NCGC) out of all gastric cancer cases were computed by country, sex and age group. Proportions were subsequently applied to the estimated numbers of oesophageal and gastric cancer cases from GLOBOCAN 2018. Age-standardised incidence rates (ASR) were calculated.
Results
In 2018, there were an estimated 572 000 new cases of oesophageal cancer worldwide, 85 000 OACs (ASR 0.9 per 100 000, both sexes combined) and 482 000 OSCCs (ASR 5.3). Out of 1.03 million gastric cancers, there were an estimated 181 000 cases of CGC (ASR 2.0) and 853 000 cases of NCGC (ASR 9.2). While the highest incidence rates of OSCC, CGC and NCGC were observed in Eastern Asia (ASRs 11.1, 4.4 and 17.9, respectively), rates of OAC were highest in Northern Europe (ASR 3.5). While globally OSCC and NCGC remain the most common types of oesophageal and gastric cancer, respectively, rates of OAC exceed those of OSCC in an increasing number of high-income countries.
Conclusions
These updated estimates of the global burden of oesophageal and gastric cancer by subtype and site suggest an ongoing transition in epidemiological patterns. This work will serve as a cornerstone for policy-making and will aid in developing appropriate cancer control strategies.
Context/Objective
Increases of thyroid cancer (TC) incidence emerged in the last decades in several countries. This study aimed to estimate time trends of TC incidence in India and the proportion of TC cases potentially attributable to overdiagnosis by sex, age, and area.
Design
TC cases aged 0-74 years reported to Indian cancer registries during 2006-2014 were included. Age-standardized incidence rates (ASR) and TC overdiagnosis were estimated by sex, period, age, and area.
Results
Between 2006-2008 and 2012-2014, the ASRs for TC in India increased from 2.5 to 3.5/100,000 women (+37%) and from 1.0 to 1.3/100.000 men (+27%). However, up to a 10-fold difference was found among regions in both sexes. Highest ASRs emerged in Thiruvananthapuram (14.6/100,000 women and 4.1/100,000 men in 2012-2014), with 93% increase in women and 64% in men compared to 2006-2008. No evidence of overdiagnosis was found in Indian men. Conversely, overdiagnosis accounted for 51% of TC in Indian women: 74% in those aged <35 years, 50% at ages 35-54 years, and 30% at ages 55-64 years. In particular, 80% of TC overdiagnosis in women emerged in Thiruvananthapuram, while none or limited evidence of overdiagnosis emerged in Kamrup, Dibrugarh, Bhopal, and Sikkim.
Conclusions
Relatively high and increasing TC ASRs emerged in Indian regions where better access to healthcare was reported. In India, as elsewhere, new strategies are needed to discourage opportunistic screening practice, particularly in young women, and to avoid unnecessary and expensive treatments. Present results may serve as a warning also for other transitioning countries.
Background:
There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers.
Methods:
A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants.
Results:
Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9.
Conclusions:
In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.).
Importance
Colorectal cancer (CRC) incidence and mortality among individuals younger than 50 years (early-onset CRC) are increasing. The reasons for such increases are largely unknown, although the increasing prevalence of obesity may be partially responsible.
Objective
To investigate prospectively the association between obesity and weight gain since early adulthood with the risk of early-onset CRC.
Design, Setting, and Participants
The Nurses’ Health Study II is a prospective, ongoing cohort study of US female nurses aged 25 to 42 years at study enrollment (1989). A total of 85 256 women free of cancer and inflammatory bowel disease at enrollment were included in this analysis, with follow-up through December 31, 2011. Validated anthropomorphic measures and lifestyle information were self-reported biennially. Statistical analysis was performed from June 12, 2017, to June 28, 2018.
Exposures
Current body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), BMI at 18 years of age, and weight gain since 18 years of age.
Main Outcomes and Measures
Relative risk (RR) for incident early-onset CRC.
Results
Among the 85 256 women studied, 114 cases of early-onset CRC were documented (median age at diagnosis, 45 years; interquartile range, 41-47 years) during 1 196 452 person-years of follow-up. Compared with women with a BMI of 18.5 to 22.9, the multivariable RR was 1.37 (95% CI, 0.81-2.30) for overweight women (BMI, 25.0-29.9) and 1.93 (95% CI, 1.15-3.25) for obese women (BMI, ≥30.0). The RR for each 5-unit increment in BMI was 1.20 (95% CI, 1.05-1.38; P = .01 for trend). Similar associations were observed among women without a family history of CRC and without lower endoscopy within the past 10 years. Both BMI at 18 years of age and weight gain since 18 years of age contributed to this observation. Compared with women with a BMI of 18.5 to 20.9 at 18 years of age, the RR of early-onset CRC was 1.32 (95% CI, 0.80-2.16) for women with a BMI of 21.0 to 22.9 and 1.63 (95% CI, 1.01-2.61) for women with a BMI of 23.0 or greater at 18 years of age (P = .66 for trend). Compared with women who had gained less than 5.0 kg or had lost weight, the RR of early-onset CRC was 1.65 (95% CI, 0.96-2.81) for women gaining 20.0 to 39.9 kg and 2.15 (95% CI, 1.01-4.55) for women gaining 40.0 kg or more (P = .007 for trend).
Conclusions and Relevance
Obesity was associated with an increased risk of early-onset CRC among women. Further investigations among men and to elucidate the underlying biological mechanisms are warranted.
The incidence of prostate cancer has been increasing worldwide in recent years. The GLOBOCAN project showed that prostate cancer was the second most frequently diagnosed cancer and the fifth leading cause of cancer mortality among men worldwide in 2012. This trend has been growing even in Asian countries, where the incidence had previously been low. However, the accuracy of data about incidence and mortality as a result of prostate cancer in some Asian countries is limited. The cause of this increasing trend is multifactorial. One possible explanation is changes in lifestyles due to more Westernized diets. The incidence is also statistically biased by the wide implementation of early detection systems and the accuracy of national cancer registration systems, which are still immature in most Asian countries. Mortality rate decreases in Australia, New Zealand and Japan since the 1990s are possibly due to the improvements in treatment and/or early detection efforts employed. However, this rate is increasing in the majority of other Asian countries. Studies of latent and incidental prostate cancer provide less biased information. The prevalence of latent and incidental prostate cancer in contemporary Japan and Korea is similar to those in Western countries, suggesting the influence of lifestyle changes on carcinogenesis. Many studies reported evidence of both congenital and acquired risk factors for carcinogenesis of prostate cancer. Recent changes in the acquired risk factors might be associated with the increasing occurrence of prostate cancer in Asian countries. This trend could continue, especially in developing Asian countries.
The global burden of non-communicable diseases (NCDs) is growing, and there is an urgent need to estimate the costs and benefits of an investment strategy to prevent and control NCDs. Results from an investment-case analysis can provide important new evidence to inform decision making by governments and donors. We propose a methodology for calculating the economic benefits of investing in NCDs during the Sustainable Development Goals (SDGs) era, and we applied this methodology to cardiovascular disease prevention in 20 countries with the highest NCD burden. For a limited set of prevention interventions, we estimated that US1·50 per capita per year and would avert 15 million deaths, 8 million incidents of ischaemic heart disease, and 13 million incidents of stroke in the 20 countries. Benefit-cost ratios varied between interventions and country-income levels, with an average ratio of 5·6 for economic returns but a ratio of 10·9 if social returns are included. Investing in cardiovascular disease prevention is integral to achieving SDG target 3.4 (reducing premature mortality from NCDs by a third) and to progress towards SDG target 3.8 (the realisation of universal health coverage). Many countries have implemented cost-effective interventions at low levels, so the potential to achieve these targets and strengthen national income by scaling up these interventions is enormous.
Introduction:
Pancreatic cancer currently ranks below female breast cancer in terms of the number of deaths in both males and females in the EU. While breast cancer mortality rates have been declining in many higher income EU countries during recent decades, rates of pancreatic cancer in contrast are either stable or moderately increasing; a comparative analysis of the short-term future rates of both is warranted.
Methods:
We extracted the annual number of deaths from cancers of the pancreas and breast by gender together with population at risk in each of 28 countries of the EU for the period 2001-2010. We fitted cancer- and gender-specific time-linear regression models and predicted deaths from pancreatic and breast cancer mortality for the years 2011-2025.
Results:
We estimated that by the year 2017 more deaths from pancreatic cancer will occur (91 500 annual deaths) than breast cancer (91 000) in the EU. By 2025, deaths from cancer of the pancreas are predicted to be 25% higher (111 500 and 90 000, respectively). Pancreatic cancer may become the third leading cause of death from cancer in the EU after lung and colorectal cancers.
Conclusion:
Although strategies may emerge in the near future that will enhance the prospects of improving the very poor five-year survival from pancreatic cancer, coordinated efforts are necessary to reduce the foreseeable high mortality burden of disease within the EU.
Context:
Bladder cancer has become a common cancer globally, with an estimated 430 000 new cases diagnosed in 2012.
Objective:
We examine the most recent global bladder cancer incidence and mortality patterns and trends, the current understanding of the aetiology of the disease, and specific issues that may influence the registration and reporting of bladder cancer.
Evidence acquisition:
Global bladder cancer incidence and mortality statistics are based on data from the International Agency for Research on Cancer and the World Health Organisation (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organisation Mortality).
Evidence synthesis:
Bladder cancer ranks as the ninth most frequently-diagnosed cancer worldwide, with the highest incidence rates observed in men in Southern and Western Europe, North America, as well in certain countries in Northern Africa or Western Asia. Incidence rates are consistently lower in women than men, although sex differences varied greatly between countries. Diverging incidence trends were also observed by sex in many countries, with stabilising or declining rates in men but some increasing trends seen for women. Bladder cancer ranks 13th in terms of deaths ranks, with mortality rates decreasing particularly in the most developed countries; the exceptions are countries undergoing rapid economic transition, including in Central and South America, some central, southern, and eastern European countries, and the Baltic countries.
Conclusions:
The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking, although infection with Schistosoma haematobium and other risk factors are major causes in selected populations. Differences in coding and registration practices need to be considered when comparing bladder cancer statistics geographically or over time.
Patient summary:
The main risk factor for bladder cancer is tobacco smoking. The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking.
Purpose:
A dramatic improvement in the survival of patients with chronic myeloid leukemia (CML) occurred after the introduction of imatinib mesylate, the first tyrosine kinase inhibitor (TKI). We assessed how these changes affected the life expectancy of patients with CML and life-years lost as a result of CML between 1973 and 2013 in Sweden.
Materials and methods:
Patients recorded as having CML in the Swedish Cancer Registry from 1973 to 2013 were included in the study and followed until death, censorship, or end of follow-up. The life expectancy and loss in expectation of life were predicted from a flexible parametric relative survival model.
Results:
A total of 2,662 patients with CML were diagnosed between 1973 and 2013. Vast improvements in the life expectancy of these patients were seen over the study period; larger improvements were seen in the youngest ages. The great improvements in life expectancy translated into great reductions in the loss in expectation of life. Patients of all ages diagnosed in 2013 will, on average, lose < 3 life-years as a result of CML.
Conclusion:
Imatinib mesylate and new TKIs along with allogeneic stem cell transplantation and other factors have contributed to the life expectancy in patients with CML approaching that of the general population today. This will be an important message to convey to patients to understand the impact of a CML diagnosis on their life. In addition, the increasing prevalence of patients with CML will have a great effect on future health care costs as long as continuous TKI treatment is required.