Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether k...Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.展开更多
Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through iso...Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.展开更多
Objectives Primary prevention targeting modifiable risk factors would reduce the global burden of colorectal cancer,but the quantitative results are uncertain.We aimed to assess the global burden of colorectal cancer ...Objectives Primary prevention targeting modifiable risk factors would reduce the global burden of colorectal cancer,but the quantitative results are uncertain.We aimed to assess the global burden of colorectal cancer attributed to modifiable lifestyle factors and quantify the potential increase in life expectancy resulting from the elimination of these risk factors.Methods Based on the Global Burden of Disease Study 2021,we examined colorectal cancer deaths and disability-adjusted life years attributed to modifiable risk factors(including smoking,diet low in whole grains,diet low in milk,diet high in red meat,diet low in calcium,diet high in processed meat,and diet low in fiber)at the global,regional,and national levels from 1990 to 2021.The abridged period life table method was utilized to quantify the potential gain in life expectancy from eliminating these risk factors.Results Globally in 2021,57.1%of colorectal cancer deaths and 56.4%of disability-adjusted life years were preventable,with rates of 7.55(4.94–9.64)and 174.67(114.54–222.24)per 100,000 population,respectively.The modifiable burden has diminished in the high,high-middle,and low socio-demographic index quintiles and remained steady in the middle one.However,there is a concerning increase in the low-middle one.In 2021,the elimination of global colorectal cancer attributed to modifiable factors would increase the life expectancy for males and females by 0.107 and 0.109 years,respectively.Conclusion Our results quantitatively demonstrate the substantial burden reduction in colorectal cancer and the significant gain in life expectancy that can be achieved by eliminating modifiable lifestyle factors.展开更多
Objective:To understand the current status and changing trends in the lifetime risk of residents in Henan Province,China to develop and die from cancer.Methods:Lifetime risk was estimated using the Adjusted for Multip...Objective:To understand the current status and changing trends in the lifetime risk of residents in Henan Province,China to develop and die from cancer.Methods:Lifetime risk was estimated using the Adjusted for Multiple Primaries(AMP)method,incorporating cancer incidence,mortality,and all-cause mortality data from 55 cancer registries in Henan Province,China.Estimates were calculated overall and stratified by gender and area.The annual percent change(APC)in lifetime risk from 2010 to 2020,stratified by gender and cancer site,was estimated using a log-linear model.Results:In 2020,the lifetime risk of developing and dying from cancer was 30.19%(95%CI:29.63%-30.76%)and 23.62%(95%CI:23.28%-23.95%),respectively.These estimates were higher in men,with values of 31.22%(95%CI:30.59%-31.85%)for developing cancer and 26.73%(95%CI:26.29%-27.16%)for dying from cancer,compared with women,who had values of 29.02%(95%CI:28.12%-29.91%)and 20.08%(95%CI:19.51%-20.64%),respectively.There were also geographical differences,with higher estimates in urban areas compared with rural areas.Residents had the highest lifetime risk of developing lung cancer,with a rate of 6.94%,followed by breast cancer(4.14%),stomach cancer(3.95%),esophageal cancer(3.75%),and liver cancer(2.86%).Similarly,the highest lifetime risk of dying from cancer was observed for the following sites:lung(5.99%),stomach(3.60%),esophagus(3.39%),liver(2.78%),and colorectum(1.55%).Overall,the lifetime risk of developing cancer increased,with an APC of 0.75%(P<0.05).Varying trends were observed across different cancer sites.There were gradual decreases in nasopharynx,esophagus,stomach,and liver cancers.Conversely,increasing trends were noted for most other sites,with the highest APCs observed in thyroid,prostate,lymphoma,kidney,and gallbladder cancers.Conclusion:The lifetime risks of developing and dying from cancer were 30.19%and 23.62%,respectively.Variations in cancer risk across different regions,genders,specific cancer sites,and over calendar years provide important information for cancer prevention and policy making in the population.展开更多
Objective:To evaluate the impact of government-organized screening on the economic burden among patients with cervical cancer and precancerous lesions,and explore mediating pathways across diagnosis,initial treatment,...Objective:To evaluate the impact of government-organized screening on the economic burden among patients with cervical cancer and precancerous lesions,and explore mediating pathways across diagnosis,initial treatment,radiotherapy/chemotherapy,follow-up,and recurrence/progression/metastasis.Methods:A multicentre,nationwide survey across 5 disease courses was conducted from 26 hospitals in China.Multivariable regression and structural equation modeling were used to assess the effects of government-organized screening on economic burden by comparing government-organized screening with workplace check-up,self-paid check-up,and symptom-based detection.Results:Workplace check-up,self-paid check-up,and symptom-based detection were associated with progressively higher costs across diagnosis[β:1.10,95%confidence interval(CI):0.54±1.67;β:1.46,95%CI:1.00±1.92;andβ:1.68,95%CI:1.25±2.11,respectively],initial treatment(β:0.36,95%CI:0.18±0.55;β:0.51,95%CI:0.35±0.66;andβ:0.56,95%CI:0.42±0.70,respectively),and follow-up(β:0.63,95%CI:0.38±0.88;β:0.83,95%CI:0.61±1.04;andβ:0.85,95%CI:0.65±1.06,respectively)compared to government-organized screening(all P<0.05).Earlier clinical staging and greater use of lower-level hospitals mediated 44.74%±54.97%of cost differences in diagnosis,73.27%±85.04%in initial treatment,and 30.38%±54.73%in follow-up.Fifteen percent of the cost differences during initial treatment were related to lower overtreatment for precancerous lesions.Conclusions:Government-led cervical cancer screening was associated with lower economic burden with pathways involving earlier-stage diagnosis,reduced overtreatment,and decreased reliance on higher-level hospitals,suggesting potential clinical benefits,efficient resource use,and improved equity in cancer care.展开更多
1.Introduction With an estimate of 19,976,499 newly diagnosed cases and 9,743,832 deaths occurred in 2022 worldwide,cancer continues to impose a significant health and economic burden worldwide.1 The development of ca...1.Introduction With an estimate of 19,976,499 newly diagnosed cases and 9,743,832 deaths occurred in 2022 worldwide,cancer continues to impose a significant health and economic burden worldwide.1 The development of cancer is a complex interplay between genetic and environmental factors.2 In addition to genetic modifications,there is a growing body of evidence suggesting that epigenetic changes,which influence gene expression without modifying the DNA sequence,are playing an increasingly significant role in the development of cancer.DNA methylation,a key epigenetic mechanism,has been notably implicated in the early stages of cancer development,positioning it as a potential biomarker for cancer risk assessment.3 Studies have identified a diverse array of DNA methylation biomarkers for the early detection and diagnosis of cancer,utilizing DNA extracted from tissues,blood,stool,urine,and bowel lavage fluid.4 Research of DNA methylation has focused on two primary sources:peripheral blood mononuclear cell or white blood cell(WBC)DNA methylation,5 linked to cancer susceptibility and tumor-derived cell-free DNA(cfDNA)methylation,6 which has gained significant attention in recent years as a promising biomarker for cancer screening and diagnosis.展开更多
Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesio...Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.展开更多
BACKGROUND Pancreatic cancer has an extremely poor prognosis.Although surgery is the firstline treatment for pancreatic cancer,its role is ultimately limited because patients often present too late for resection.Thus,...BACKGROUND Pancreatic cancer has an extremely poor prognosis.Although surgery is the firstline treatment for pancreatic cancer,its role is ultimately limited because patients often present too late for resection.Thus,multidisciplinary treatment approaches are needed.In particular,chemotherapy,targeted therapy,and immunotherapy can be ineffective for locally advanced pancreatic cancer(LAPC)because of its resistance to these modalities,but cryoablation has shown significant promise for treating this entity and prolonging survival.AIM To investigate the safety and efficacy of cryoablation for LAPC.METHODS Clinical and laboratory data,including surgical procedure,postoperative complications,immunobiochemical markers(e.g.,carbohydrate antigen 19-9),and followup visits,of 24 LAPC patients treated with cryoablation at the department of hepatobiliary and pancreatic surgery of our hospital from January 2023 to December 2024 were retrospectively analyzed.RESULTS Surgery was smooth in all patients,with no perioperative deaths.Postoperative pancreatic fistulas occurred in 18 patients(75.0%),including biochemical leak in 14 cases and grade B(fistula)in 4 cases.Three patients(12.5%)had delayed gastric emptying.The carbohydrate antigen 19-9 level remained low on postoperative day 30(P<0.05).Immune markers(natural killer cells and tumor necrosis factor-alpha)significantly increased on days 7 and 30(P<0.01 or P<0.05),whereas cluster of differentiation CD4+T cells levels on day 30 significantly differed from baseline.Day 30 pain scores were significantly lower than preoperative ones(P<0.01).Tumor volume was reduced on postoperative computed tomography.Survival was prolonged.The overall survival time of LAPC patients treated with cryoablation was 16.8 months.CONCLUSION Cryoablation can directly inactivate LAPC and boost immunity,thus delaying tumor progression,alleviating pain,improving quality of life,and prolonging survivals.Therefore,it is a safe and effective treatment option for LAPC.展开更多
BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth fac...BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.展开更多
Objective:To describe temporal changes associated with deployment of an optical character recognition(OCR)-enabled OneIdentity(One-ID)digital platform for rural cervical cancer screening,focusing on over-screening rat...Objective:To describe temporal changes associated with deployment of an optical character recognition(OCR)-enabled OneIdentity(One-ID)digital platform for rural cervical cancer screening,focusing on over-screening rates,CIN2+detection,colposcopy follow-up,and CIN2+management.Methods:A multi-county pre-post observational study was conducted in six rural counties in Shanxi,Yunnan,and Sichuan Provinces(2021±2024),encompassing 153,978 encounters.The digital platform integrates OCR identity capture,deterministic One-ID linkage,and real-time duplicate alerts.Over-screening proportions before and after digital deployment were compared,changes in CIN2+detection rate were evaluated,and colposcopy follow-up and CIN2+management were assessed.Differences were tested withχ2 or Fisher's exact tests.Results:Among 153,978 encounters,the proportion of over-screening decreased from 12.64%in 2023 to 0.17%in 2024 with an absolute reduction of 12.17%(95%CI:11.94±12.40;P<0.001).The share of women receiving a first screening within the preceding 3 y increased from 78.3%to 88.2%(P<0.001).Colposcopy completion improved from 64.1%to 84.9%.The CIN2+detection rate rose from 0.35%(2021±2023 pooled)to 0.67%in 2024(P<0.001)and CIN2+management completion increased from 56.0%to 76.2%(95%CI:13.3±27.2;P<0.001).These improvements were consistent across age groups,counties,and screening strategies.Conclusions:The OCR-enabled One-ID platform substantially reduced over-screening,increased CIN2+detection rate,and strengthened case follow-up/management,particularly where baseline tracking was weak,supporting scalable digital reinforcement of rural screening programmes.展开更多
Objective:Ozone(O_(3))is recognized as a predominant and increasingly prevalent gaseous pollutant contributing to the Global Burden of Disease.However,its effect on the development of lung cancer has not been adequate...Objective:Ozone(O_(3))is recognized as a predominant and increasingly prevalent gaseous pollutant contributing to the Global Burden of Disease.However,its effect on the development of lung cancer has not been adequately acknowledged.Methods:Based on Health Evaluation And risk Reduction through nationwide Teamwork(ChinaHEART),a nationwide,population-based cohort study,2,006,878 participants living in 20,159 communities or villages were passively followed for the incidence of lung cancer through a linkage of data with the National Central Cancer Registry.The average O_(3) levels over ten years from the year of enrolment in their respective localities were determined based on geographic coordinates.We conducted Cox proportional-hazards regression models to assess the independent hazard ratios(HRs)associated with O_(3) exposure and the development of lung cancer.Results:During the follow-up of 4.93 million person-years,4555 new cases of lung cancer were identified.After adjusting for participant characteristics and other environmental factors,we observed a significant positive association between ambient O_(3) exposure and lung cancer.Compared with participants in the quartile 1 of O_(3),HRs and 95%confidence intervals(CI)for the other three quartiles were 1.09(95%CI:1.00-1.17),1.17(95%CI:1.06-1.29)and 1.42(95%CI:1.26-1.59),respectively.Conclusions:Long-term exposure to ambient O_(3) is associated with a substantially higher risk of lung cancer.Further studies are needed to explore its pathogenic mechanisms,as well as to evaluate measures for exposure protection or harm mitigation at the individual or population level.展开更多
Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic ...Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
Ovarian cancer(OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that d...Ovarian cancer(OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination,pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy,pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology,primary prevention, early detection, and possibly even therapeutic strategies.展开更多
Objective： Colorectal cancer is the third most common type of cancer and the fourth leading cause of cancer-related death in the world. This article provides the most up-to-date overview of colorectal cancer burden i...Objective： Colorectal cancer is the third most common type of cancer and the fourth leading cause of cancer-related death in the world. This article provides the most up-to-date overview of colorectal cancer burden in China. Methods： Totally 234 cancer registries submitted data of 2011 to the National Central Cancer Registry （NCCR）. Qualified data from 177 registries was pooled and analyzed. The crude incidence and mortality rates of colorectal cancer were calculated by age, gender and geographic area. The numbers of new cases and deaths were estimated using the 5-year age-specific cancer incidence/mortality rates and the corresponding populations. China census in 2000 and Segi＇s world population were applied for age standardized rates. Results： The estimate of new cases diagnosed with colorectal cancer of China in 2011 was 310,244 （178,404 for males and 131,840 for females, 195,117 in urban areas and 115,128 in rural areas）, accounting for 9.20% of overall new cancer cases. The crude incidence of colorectal cancer ranked fourth in all cancer sites with rate of 23.03/100,000 （25.83/100,000 for males and 20.08/100,000 for female, 28.25/100,000 in urban areas and 17.54/100,000 in rural areas）. The age-standardized rates by China population and by World population were 16.79/100,000 and 16.52/100,000, respectively. The estimated number of colorectal cancer deaths of China in 2011 was 149,722 （86,427 for males and 63,295 for females, 91,682 in urban areas and 58,040 in rural areas）, accounting for 7.09% of overall cancer deaths. The crude mortality rate for colorectal cancer ranked fifth leading cause of cancer-related death in all cancer sites with rate of 11.11/100,000 （12.51/100,000 for males and 9.64/100,000 for female, 13.27/100,000 in urban areas and 8.84/100,000 in rural areas）. The age-standardized rates by China population and by World population for mortality were 7.77/100,000 and 7.66/100,000, respectively. For both of incidence and mortality, the rates of colorectal cancer were much higher in males than in females, and in rural areas than in urban areas. The rate of colorectal cancer increased greatly with age, especially after 40 or 45 years old. Conclusions： Colorectal cancer is a relative common cancer in China, especially for males in urban areas. Targeted prevention and early detection programs should be carried out.展开更多
Screening and early diagnosis of gastric cancer play important roles in reducing the mortality of gastric cancer. A vast amount of study data on gastric cancer screening and early diagnosis has been accumulated in and...Screening and early diagnosis of gastric cancer play important roles in reducing the mortality of gastric cancer. A vast amount of study data on gastric cancer screening and early diagnosis has been accumulated in and out of China in the past decades. The practice of gastric cancer screening has also been efficiently carried out in different countries and regions. However, no widely accepted principle of population screening for gastric cancer has been developed yet. Screening for gastric cancer requires extensive exploration both theoretically and practically. This article focuses on the method and program of gastric cancer screening based on population. Moreover, the current situation of gastric cancer screening and its evaluation are evaluated.展开更多
The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, ...The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound sys-temic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma(PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.展开更多
Objective: Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics...Objective: Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics,management and outcomes of young breast cancer patients over time.Methods: Females under 40 years of age diagnosed with breast cancer during the periods 1999-2017 and1999-2015 were identified in the Fudan University Shanghai Cancer Center(FUSCC) and the population-based Surveillance, Epidemiology, and End Results(SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up.Results: The proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ(DCIS)(from 8.8% to 16.9%;P<0.0001) and it remained stable in SEER cohort. The proportion of T1-stage tumors increased dramatically in the FUSCC cohort(from 35.3% to 41.9%;P=0.008), whereas it decreased in SEER cohort(from 42.4% to 33.0%;P<0.0001). The percentage of estrogen receptor(ER)-positive cancers was consistently increased in both the invasive ductal carcinoma(IDC) and DCIS patients in the two cohorts. Breastconserving surgery and immediate implant reconstruction after mastectomy both exhibited increased use over time in the FUSCC cohort. Both the FUSCC and SEER cohorts showed a significantly better prognosis in the recent time period.Conclusions: With the increased early-stage and ER-positive diseases in young patients as well as better systemic treatment strategies, improved survival has been observed in recent years. There has been a substantial deescalation in surgical therapies in young breast cancer patients.展开更多
In this review,we offer a concise overview of liver cancer epidemiology in China and worldwide from the official databases of GLOBOCAN 2020 and the National Cancer Registry in China.We also summarized the evidence for...In this review,we offer a concise overview of liver cancer epidemiology in China and worldwide from the official databases of GLOBOCAN 2020 and the National Cancer Registry in China.We also summarized the evidence for the main risk factors associated with liver cancer risk and discuss strategies implemented in China to control the liver cancer burden.Overall,liver cancer was the sixth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020.Although China contributed to nearly half of cases across the world alone,the incidence and mortality rates of liver cancer presented a declining trend owing to the persistent efforts from the governments at all levels.The current liver cancer burden in China still faces an arduous challenge due to the relatively large population base as well as the substantially low survival rate(12.1%).To better control the liver cancer burden with the lowest cost,specific measures should be conducted by reducing exposure to established risk factors such as hepatitis B infection and aflatoxin.The promotion of surveillance is also an important method to prolong the survival of liver cancer.This review will provide basic information for future direction on the control of liver cancer burden.展开更多
China is faced with heavy burdens caused by lung cancer,which has climbed to the top of both cancer incidence and mortality spectrums.The age-standardized rates of incidence and mortality have shown a trend of gradual...China is faced with heavy burdens caused by lung cancer,which has climbed to the top of both cancer incidence and mortality spectrums.The age-standardized rates of incidence and mortality have shown a trend of gradual uptrends in the last decades,while the crude rates rise much quickly due to the aging of population.Although the improvement in health care has contributed to better survival of lung cancer,its prognosis is still challenging.Apart from the common risk factors such as tobacco use,air pollution,and occupational hazards,some specific factors like Chinese-style cooking also have posed great threats to human health.In light of such national conditions,specific interventions should be conducted to curb the burden of lung cancer including smoking cessation,improvement of air quality,early detection and effective treatment of lung cancer.展开更多
基金funded by the National Natural Science Foundation of China(No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501400-2023ZD0501402)+4 种基金Beijing Hospitals Authority’s Ascent Plan(DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZLRK202325)China Postdoctoral Science Foundation(2024M760152)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(No.BMU2022XKQ004)Science Foundation of Peking University Cancer Hospital(Nos.BJCH2024BJ02,XKFZ2410,BJCH2025CZ04,and 2022-27)。
文摘Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.
基金supported by the National Natural Science Foundation of China(Grant No.32170738)the National Medical Research Council of Singapore(Grant No.NMRC/CBRG/0013/2012).
文摘Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.
基金supported by the National Natural Science Foundation of China(grant number:82404340)the CAMS Innovation Fund for Medical Science(grant number:2021-I2M-1–067)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(grant number:LTGY23H260004)the Beijing Natural Science Foundation(grant number:Z240004).
文摘Objectives Primary prevention targeting modifiable risk factors would reduce the global burden of colorectal cancer,but the quantitative results are uncertain.We aimed to assess the global burden of colorectal cancer attributed to modifiable lifestyle factors and quantify the potential increase in life expectancy resulting from the elimination of these risk factors.Methods Based on the Global Burden of Disease Study 2021,we examined colorectal cancer deaths and disability-adjusted life years attributed to modifiable risk factors(including smoking,diet low in whole grains,diet low in milk,diet high in red meat,diet low in calcium,diet high in processed meat,and diet low in fiber)at the global,regional,and national levels from 1990 to 2021.The abridged period life table method was utilized to quantify the potential gain in life expectancy from eliminating these risk factors.Results Globally in 2021,57.1%of colorectal cancer deaths and 56.4%of disability-adjusted life years were preventable,with rates of 7.55(4.94–9.64)and 174.67(114.54–222.24)per 100,000 population,respectively.The modifiable burden has diminished in the high,high-middle,and low socio-demographic index quintiles and remained steady in the middle one.However,there is a concerning increase in the low-middle one.In 2021,the elimination of global colorectal cancer attributed to modifiable factors would increase the life expectancy for males and females by 0.107 and 0.109 years,respectively.Conclusion Our results quantitatively demonstrate the substantial burden reduction in colorectal cancer and the significant gain in life expectancy that can be achieved by eliminating modifiable lifestyle factors.
基金supported by Henan Province Science and Technology Tackling Key Issues Project(grant number:232102310166).
文摘Objective:To understand the current status and changing trends in the lifetime risk of residents in Henan Province,China to develop and die from cancer.Methods:Lifetime risk was estimated using the Adjusted for Multiple Primaries(AMP)method,incorporating cancer incidence,mortality,and all-cause mortality data from 55 cancer registries in Henan Province,China.Estimates were calculated overall and stratified by gender and area.The annual percent change(APC)in lifetime risk from 2010 to 2020,stratified by gender and cancer site,was estimated using a log-linear model.Results:In 2020,the lifetime risk of developing and dying from cancer was 30.19%(95%CI:29.63%-30.76%)and 23.62%(95%CI:23.28%-23.95%),respectively.These estimates were higher in men,with values of 31.22%(95%CI:30.59%-31.85%)for developing cancer and 26.73%(95%CI:26.29%-27.16%)for dying from cancer,compared with women,who had values of 29.02%(95%CI:28.12%-29.91%)and 20.08%(95%CI:19.51%-20.64%),respectively.There were also geographical differences,with higher estimates in urban areas compared with rural areas.Residents had the highest lifetime risk of developing lung cancer,with a rate of 6.94%,followed by breast cancer(4.14%),stomach cancer(3.95%),esophageal cancer(3.75%),and liver cancer(2.86%).Similarly,the highest lifetime risk of dying from cancer was observed for the following sites:lung(5.99%),stomach(3.60%),esophagus(3.39%),liver(2.78%),and colorectum(1.55%).Overall,the lifetime risk of developing cancer increased,with an APC of 0.75%(P<0.05).Varying trends were observed across different cancer sites.There were gradual decreases in nasopharynx,esophagus,stomach,and liver cancers.Conversely,increasing trends were noted for most other sites,with the highest APCs observed in thyroid,prostate,lymphoma,kidney,and gallbladder cancers.Conclusion:The lifetime risks of developing and dying from cancer were 30.19%and 23.62%,respectively.Variations in cancer risk across different regions,genders,specific cancer sites,and over calendar years provide important information for cancer prevention and policy making in the population.
基金supported by the Bill&Melinda Gates Foundation(Grant no.OPP1216421)CAMS Innovation Fund for Medical Sciences[CIFMS](Grant no.2021-I2M-1-004)。
文摘Objective:To evaluate the impact of government-organized screening on the economic burden among patients with cervical cancer and precancerous lesions,and explore mediating pathways across diagnosis,initial treatment,radiotherapy/chemotherapy,follow-up,and recurrence/progression/metastasis.Methods:A multicentre,nationwide survey across 5 disease courses was conducted from 26 hospitals in China.Multivariable regression and structural equation modeling were used to assess the effects of government-organized screening on economic burden by comparing government-organized screening with workplace check-up,self-paid check-up,and symptom-based detection.Results:Workplace check-up,self-paid check-up,and symptom-based detection were associated with progressively higher costs across diagnosis[β:1.10,95%confidence interval(CI):0.54±1.67;β:1.46,95%CI:1.00±1.92;andβ:1.68,95%CI:1.25±2.11,respectively],initial treatment(β:0.36,95%CI:0.18±0.55;β:0.51,95%CI:0.35±0.66;andβ:0.56,95%CI:0.42±0.70,respectively),and follow-up(β:0.63,95%CI:0.38±0.88;β:0.83,95%CI:0.61±1.04;andβ:0.85,95%CI:0.65±1.06,respectively)compared to government-organized screening(all P<0.05).Earlier clinical staging and greater use of lower-level hospitals mediated 44.74%±54.97%of cost differences in diagnosis,73.27%±85.04%in initial treatment,and 30.38%±54.73%in follow-up.Fifteen percent of the cost differences during initial treatment were related to lower overtreatment for precancerous lesions.Conclusions:Government-led cervical cancer screening was associated with lower economic burden with pathways involving earlier-stage diagnosis,reduced overtreatment,and decreased reliance on higher-level hospitals,suggesting potential clinical benefits,efficient resource use,and improved equity in cancer care.
基金supported by the Beijing Nova Program of Science and Technology(grant number:20230484397)the National Natural Science Foundation of China(grant number:82273726).
文摘1.Introduction With an estimate of 19,976,499 newly diagnosed cases and 9,743,832 deaths occurred in 2022 worldwide,cancer continues to impose a significant health and economic burden worldwide.1 The development of cancer is a complex interplay between genetic and environmental factors.2 In addition to genetic modifications,there is a growing body of evidence suggesting that epigenetic changes,which influence gene expression without modifying the DNA sequence,are playing an increasingly significant role in the development of cancer.DNA methylation,a key epigenetic mechanism,has been notably implicated in the early stages of cancer development,positioning it as a potential biomarker for cancer risk assessment.3 Studies have identified a diverse array of DNA methylation biomarkers for the early detection and diagnosis of cancer,utilizing DNA extracted from tissues,blood,stool,urine,and bowel lavage fluid.4 Research of DNA methylation has focused on two primary sources:peripheral blood mononuclear cell or white blood cell(WBC)DNA methylation,5 linked to cancer susceptibility and tumor-derived cell-free DNA(cfDNA)methylation,6 which has gained significant attention in recent years as a promising biomarker for cancer screening and diagnosis.
基金funded by the National Natural Science Foundation of China(Grant No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant Nos.2023ZD0501400-2023ZD0501402)+3 种基金Beijing Hospitals Authority’s Ascent Plan(Grant No.DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(Grant No.ZLRK202325)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(Grant No.BMU2022XKQ004)the Science Foundation of Peking University Cancer Hospital(Grant Nos.BJCH2024BJ02,XKFZ2410,and 2022-27).
文摘Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.
文摘BACKGROUND Pancreatic cancer has an extremely poor prognosis.Although surgery is the firstline treatment for pancreatic cancer,its role is ultimately limited because patients often present too late for resection.Thus,multidisciplinary treatment approaches are needed.In particular,chemotherapy,targeted therapy,and immunotherapy can be ineffective for locally advanced pancreatic cancer(LAPC)because of its resistance to these modalities,but cryoablation has shown significant promise for treating this entity and prolonging survival.AIM To investigate the safety and efficacy of cryoablation for LAPC.METHODS Clinical and laboratory data,including surgical procedure,postoperative complications,immunobiochemical markers(e.g.,carbohydrate antigen 19-9),and followup visits,of 24 LAPC patients treated with cryoablation at the department of hepatobiliary and pancreatic surgery of our hospital from January 2023 to December 2024 were retrospectively analyzed.RESULTS Surgery was smooth in all patients,with no perioperative deaths.Postoperative pancreatic fistulas occurred in 18 patients(75.0%),including biochemical leak in 14 cases and grade B(fistula)in 4 cases.Three patients(12.5%)had delayed gastric emptying.The carbohydrate antigen 19-9 level remained low on postoperative day 30(P<0.05).Immune markers(natural killer cells and tumor necrosis factor-alpha)significantly increased on days 7 and 30(P<0.01 or P<0.05),whereas cluster of differentiation CD4+T cells levels on day 30 significantly differed from baseline.Day 30 pain scores were significantly lower than preoperative ones(P<0.01).Tumor volume was reduced on postoperative computed tomography.Survival was prolonged.The overall survival time of LAPC patients treated with cryoablation was 16.8 months.CONCLUSION Cryoablation can directly inactivate LAPC and boost immunity,thus delaying tumor progression,alleviating pain,improving quality of life,and prolonging survivals.Therefore,it is a safe and effective treatment option for LAPC.
文摘BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.
基金supported by the Chongqing Tencent Sustainable Development Foundation through the project"Comprehensive Prevention and Control Demonstration Project for Eliminating Cervical Cancer and Breast Cancer in Low Health Resource Areas of China"(Project No.SD20240904145730)by the Tencent Sustainable Social Value(SSV)Inclusive Health Lab(Project No.SSVPJ202307060001)。
文摘Objective:To describe temporal changes associated with deployment of an optical character recognition(OCR)-enabled OneIdentity(One-ID)digital platform for rural cervical cancer screening,focusing on over-screening rates,CIN2+detection,colposcopy follow-up,and CIN2+management.Methods:A multi-county pre-post observational study was conducted in six rural counties in Shanxi,Yunnan,and Sichuan Provinces(2021±2024),encompassing 153,978 encounters.The digital platform integrates OCR identity capture,deterministic One-ID linkage,and real-time duplicate alerts.Over-screening proportions before and after digital deployment were compared,changes in CIN2+detection rate were evaluated,and colposcopy follow-up and CIN2+management were assessed.Differences were tested withχ2 or Fisher's exact tests.Results:Among 153,978 encounters,the proportion of over-screening decreased from 12.64%in 2023 to 0.17%in 2024 with an absolute reduction of 12.17%(95%CI:11.94±12.40;P<0.001).The share of women receiving a first screening within the preceding 3 y increased from 78.3%to 88.2%(P<0.001).Colposcopy completion improved from 64.1%to 84.9%.The CIN2+detection rate rose from 0.35%(2021±2023 pooled)to 0.67%in 2024(P<0.001)and CIN2+management completion increased from 56.0%to 76.2%(95%CI:13.3±27.2;P<0.001).These improvements were consistent across age groups,counties,and screening strategies.Conclusions:The OCR-enabled One-ID platform substantially reduced over-screening,increased CIN2+detection rate,and strengthened case follow-up/management,particularly where baseline tracking was weak,supporting scalable digital reinforcement of rural screening programmes.
基金supported by the CAMS Innovation Fund for Med-ical Science(grant number:2021-1-I2M-011)National High Level Hospital Clinical Research Funding(grant number:2022-GSP-GG-4)Ministry of Finance of China and National Health Commission of China,the 111 Project from the Ministry of Education of China(grant number:B16005)。
文摘Objective:Ozone(O_(3))is recognized as a predominant and increasingly prevalent gaseous pollutant contributing to the Global Burden of Disease.However,its effect on the development of lung cancer has not been adequately acknowledged.Methods:Based on Health Evaluation And risk Reduction through nationwide Teamwork(ChinaHEART),a nationwide,population-based cohort study,2,006,878 participants living in 20,159 communities or villages were passively followed for the incidence of lung cancer through a linkage of data with the National Central Cancer Registry.The average O_(3) levels over ten years from the year of enrolment in their respective localities were determined based on geographic coordinates.We conducted Cox proportional-hazards regression models to assess the independent hazard ratios(HRs)associated with O_(3) exposure and the development of lung cancer.Results:During the follow-up of 4.93 million person-years,4555 new cases of lung cancer were identified.After adjusting for participant characteristics and other environmental factors,we observed a significant positive association between ambient O_(3) exposure and lung cancer.Compared with participants in the quartile 1 of O_(3),HRs and 95%confidence intervals(CI)for the other three quartiles were 1.09(95%CI:1.00-1.17),1.17(95%CI:1.06-1.29)and 1.42(95%CI:1.26-1.59),respectively.Conclusions:Long-term exposure to ambient O_(3) is associated with a substantially higher risk of lung cancer.Further studies are needed to explore its pathogenic mechanisms,as well as to evaluate measures for exposure protection or harm mitigation at the individual or population level.
基金supported by the National Science Fund for Excellent Young Scholars(NSFC-82322058)the Program of National Natural Science Foundation of China(NSFC-82103929,NSFC-82273713)+10 种基金the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the National Science Fund for Distinguished Young Scholars of Hubei Province of China(2023AFA046)the Fundamental Research Funds for the Central Universities(WHU:2042022kf1205)Fundamental Research Funds for the Central Universities(WHU:2042022kf1031)for Ying Zhuthe Fundamental Research Funds for the Central Universities(2042022rc0026,2042023kf1005)for Xiao-Ping Miaothe Knowledge Innovation Program of Wuhan(whkxjsj011,2023020201010073)for Jian-Bo Tianthe Science and Technology Innovation Seed Fund of Zhongnan Hospital of Wuhan University(znpy2019060)for Yong-Chang Weithe Distinguished Young Scholars of China(NSFC-81925032)the Key Program of National Natural Science Foundation of China(NSFC-82130098)the Youth Program of National Natural Science Foundation of China(NSFC-82003547)the Program of Health Commission of Hubei Province(WJ2023M045)。
文摘Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
文摘Ovarian cancer(OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination,pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy,pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology,primary prevention, early detection, and possibly even therapeutic strategies.
文摘Objective： Colorectal cancer is the third most common type of cancer and the fourth leading cause of cancer-related death in the world. This article provides the most up-to-date overview of colorectal cancer burden in China. Methods： Totally 234 cancer registries submitted data of 2011 to the National Central Cancer Registry （NCCR）. Qualified data from 177 registries was pooled and analyzed. The crude incidence and mortality rates of colorectal cancer were calculated by age, gender and geographic area. The numbers of new cases and deaths were estimated using the 5-year age-specific cancer incidence/mortality rates and the corresponding populations. China census in 2000 and Segi＇s world population were applied for age standardized rates. Results： The estimate of new cases diagnosed with colorectal cancer of China in 2011 was 310,244 （178,404 for males and 131,840 for females, 195,117 in urban areas and 115,128 in rural areas）, accounting for 9.20% of overall new cancer cases. The crude incidence of colorectal cancer ranked fourth in all cancer sites with rate of 23.03/100,000 （25.83/100,000 for males and 20.08/100,000 for female, 28.25/100,000 in urban areas and 17.54/100,000 in rural areas）. The age-standardized rates by China population and by World population were 16.79/100,000 and 16.52/100,000, respectively. The estimated number of colorectal cancer deaths of China in 2011 was 149,722 （86,427 for males and 63,295 for females, 91,682 in urban areas and 58,040 in rural areas）, accounting for 7.09% of overall cancer deaths. The crude mortality rate for colorectal cancer ranked fifth leading cause of cancer-related death in all cancer sites with rate of 11.11/100,000 （12.51/100,000 for males and 9.64/100,000 for female, 13.27/100,000 in urban areas and 8.84/100,000 in rural areas）. The age-standardized rates by China population and by World population for mortality were 7.77/100,000 and 7.66/100,000, respectively. For both of incidence and mortality, the rates of colorectal cancer were much higher in males than in females, and in rural areas than in urban areas. The rate of colorectal cancer increased greatly with age, especially after 40 or 45 years old. Conclusions： Colorectal cancer is a relative common cancer in China, especially for males in urban areas. Targeted prevention and early detection programs should be carried out.
文摘Screening and early diagnosis of gastric cancer play important roles in reducing the mortality of gastric cancer. A vast amount of study data on gastric cancer screening and early diagnosis has been accumulated in and out of China in the past decades. The practice of gastric cancer screening has also been efficiently carried out in different countries and regions. However, no widely accepted principle of population screening for gastric cancer has been developed yet. Screening for gastric cancer requires extensive exploration both theoretically and practically. This article focuses on the method and program of gastric cancer screening based on population. Moreover, the current situation of gastric cancer screening and its evaluation are evaluated.
基金Supported by The National Institute of Health(NIH/NCI R01CA140290-3 to Murray NR)
文摘The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound sys-temic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma(PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.
基金supported in part by grants from the Shenkang center city hospital emerging frontier technology joint research project (No. SHDC12015119)National Key R&D Program of China (No. 2017YFC1311004)
文摘Objective: Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics,management and outcomes of young breast cancer patients over time.Methods: Females under 40 years of age diagnosed with breast cancer during the periods 1999-2017 and1999-2015 were identified in the Fudan University Shanghai Cancer Center(FUSCC) and the population-based Surveillance, Epidemiology, and End Results(SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up.Results: The proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ(DCIS)(from 8.8% to 16.9%;P<0.0001) and it remained stable in SEER cohort. The proportion of T1-stage tumors increased dramatically in the FUSCC cohort(from 35.3% to 41.9%;P=0.008), whereas it decreased in SEER cohort(from 42.4% to 33.0%;P<0.0001). The percentage of estrogen receptor(ER)-positive cancers was consistently increased in both the invasive ductal carcinoma(IDC) and DCIS patients in the two cohorts. Breastconserving surgery and immediate implant reconstruction after mastectomy both exhibited increased use over time in the FUSCC cohort. Both the FUSCC and SEER cohorts showed a significantly better prognosis in the recent time period.Conclusions: With the increased early-stage and ER-positive diseases in young patients as well as better systemic treatment strategies, improved survival has been observed in recent years. There has been a substantial deescalation in surgical therapies in young breast cancer patients.
基金supported by the National Natural Science Foundation of China(No.81974492)the National Natural Science Foundation of China(No.82273721)the Sanming project of Medicine in Shenzhen(No.SZSM201911015)。
文摘In this review,we offer a concise overview of liver cancer epidemiology in China and worldwide from the official databases of GLOBOCAN 2020 and the National Cancer Registry in China.We also summarized the evidence for the main risk factors associated with liver cancer risk and discuss strategies implemented in China to control the liver cancer burden.Overall,liver cancer was the sixth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020.Although China contributed to nearly half of cases across the world alone,the incidence and mortality rates of liver cancer presented a declining trend owing to the persistent efforts from the governments at all levels.The current liver cancer burden in China still faces an arduous challenge due to the relatively large population base as well as the substantially low survival rate(12.1%).To better control the liver cancer burden with the lowest cost,specific measures should be conducted by reducing exposure to established risk factors such as hepatitis B infection and aflatoxin.The promotion of surveillance is also an important method to prolong the survival of liver cancer.This review will provide basic information for future direction on the control of liver cancer burden.
基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-2-004)Sanming Project of Medicine in Shenzhen(No.SZSM201911015)。
文摘China is faced with heavy burdens caused by lung cancer,which has climbed to the top of both cancer incidence and mortality spectrums.The age-standardized rates of incidence and mortality have shown a trend of gradual uptrends in the last decades,while the crude rates rise much quickly due to the aging of population.Although the improvement in health care has contributed to better survival of lung cancer,its prognosis is still challenging.Apart from the common risk factors such as tobacco use,air pollution,and occupational hazards,some specific factors like Chinese-style cooking also have posed great threats to human health.In light of such national conditions,specific interventions should be conducted to curb the burden of lung cancer including smoking cessation,improvement of air quality,early detection and effective treatment of lung cancer.
