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Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data

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cancer Biology & Medicine 2024年第8期21卷 712-723页

作者： Yu Zhang Chao Sheng Zhangyan Lyu Hongji Dai Fangfang Song Fengju Song Yubei Huang Kexin Chen department of epidemiology and Biostatistics Key Laboratory of Molecular Cancer EpidemiologyKey Laboratory of Prevention and Control of Human Major DiseasesMinistry of EducationNational Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin Medical UniversityTianjin 300060China

Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(Qcancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and ***: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk ***: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94;0.81, 0.73±0.90;mortality: 0.75, 0.64±0.87;0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk ***: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

关键词： Colorectal cancer screening polygenic risk score incidence mortality

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Plant-based dietary patterns and risk of esophageal cancer:A prospective cohort study spanning 17 years

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Chinese Journal of cancer Research 2024年第1期36卷 36-45页

作者： Xiaorui Zhang Feifan He Jiayue Li Ru Chen Xinqing Li Li Li Fen Liu Shaoming Wang Wenqiang Wei department of epidemiology and Health Statistics School of Public HealthBeijing Municipal Key Laboratory of Clinical EpidemiologyCapital Medical UniversityBeijing 100069China National Central cancer Registry office National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China department of cancer epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of ***: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by ***: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity ***: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

关键词： Esophageal cancer diet dietary pattern epidemiology nutrition prospective cohort study

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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

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Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao department of epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research Center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China department of cancer epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China department of epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation Center for cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly ***,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics *** a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in *** the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in *** subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras ***,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 ***,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC *** summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

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Deep insight into the B-cell associated tertiary lymphoid structure and tumor immunotherapy

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cancer Biology & Medicine 2024年第2期21卷 125-131页

作者： Jilong Yang Jin Xu Haotian Liu Wanyi Xiao Gengpu Zhang department of Bone and Soft Tissue Tumor Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Molecular Cancer EpidemiologyTianjin 300060China department of Anaesthesiology Tianjin University Tianjin HospitalTianjin 300211China

Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other *** a promising supplemental immunotherapy to mainstream method... 详细信息

关键词： immunotherapy immunity

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The Relationship Between the Atmospheric Environment and Road Traffic Fatalities — Shandong Province, China, 2012–2021

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China CDC weekly 2024年第13期6卷 267-271页

作者： Tao Wang Jie Chu Zhiying Yao Li Yang Zilong Lu Ge Tian Xiaolei Guo Cunxian Jia department of epidemiology School of Public HealthCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department for Chronic and Non-Communicable Disease control and Prevention Shandong Center for Disease Control and PreventionJinanShandong ProvinceChina

Introduction:This study aims to analyze the potential impact of the meteorological environment and air pollutants on road traffic ***:Road traffic fatality data in Shandong Province from 2012 to 2021 were obtained from the Population Death Information Registration Management *** and air pollutant data for the same period were collected from the *** Oceanic and Atmospheric Administration and the Ecological Environment Monitoring Center of Shandong Province,***’s correlation and ridge regression were used to analyze the impact of the meteorological environment and air pollutants on road traffic ***:From 2012 to 2021,there were 163,863 road traffic fatality *** results of the ridge regression analysis showed that the daily average temperature was negatively correlated with total fatalities and passengers and positively correlated with pedestrians,nonmotorized drivers,and motorized *** daily minimum temperature was negatively correlated with total fatalities and positively correlated with motorized *** daily maximum temperature was positively correlated with both pedestrian and nonmotorized *** daily accumulated precipitation was negatively correlated with *** duration was positively correlated with both nonmotorized and motorized *** particulate matter(PM_(10))and nitrogen dioxide(NO_(2))were positively correlated with total fatalities,pedestrians,and nonmotorized *** dioxide(SO_(2))was positively correlated with total fatalities but negatively correlated with nonmotorized drivers,passengers,and motorized ***:Atmospheric factors associated with the occurrence of road traffic fatalities include air temperature,daily accumulated precipitation,sunshine duration,and air pollutants such as PM_(10),NO_(2),and SO_(2).

关键词： Ecological dioxide sunshine

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Disease and Economic Burden of Kashin-Beck Disease—China,2021

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China CDC weekly 2024年第2期6卷 40-44页

作者： Silu Cui Wenjun Que Zhe Jiao Qing Deng Xufeng Zhang Yanhong Cao Ning Liu Ailin Li Alphonse Sowanou Zhe Li Tuo Wang Yang Li Jun Yu Junrui Pei NHC Key Laboratory of Etiology and epidemiology(Harbin Medical University) Key Laboratory of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceInstitute of Kashin-Beck Disease ControlCenter for Endemic Disease ControlChinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina NHC Key Laboratory of Etiology and epidemiology(Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human HealthKey Laboratory of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceInstitute of Endemic Fluorosis ControlCenter for Endemic Disease ControlChinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina

What is already known about this topic?Kashin-Beck disease(KBD)is a chronic and degenerative osteoarthropathy characterized by cartilage *** is an endemic disease that is highly prevalent among the Chinese population and poses a significant health *** is added by this report?This is the first national report on the economic burden of KBD in *** to the data from 2021,KBD has caused significant disease and economic *** most substantial reduction in healthy life expectancy was observed among patients with degree II severity and those aged 60 years and older,resulting in a total indirect economic burden of 112.74 million Chinese Yuan(CNY).What are the implications for public health practice?The results of this study will contribute to informing the development of tailored prevention and control strategies by the *** strategies will include targeted policies and recommendations for appropriate healthcare and financial subsidies,which will be based on the demographic characteristics of the endemic areas.

关键词： prevention degeneration burden

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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Cervical cancer prevention in China: where are we now, and what's next?

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cancer Biology & Medicine 2024年第3期21卷 213-217页

作者： Huijiao Yan Qiankun Wang Youlin Qiao School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100730China department of cancer epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100021China

Cervical cancer(CC) epidemiology CC, the fourth most frequently diagnosed malignancy in women worldwide, is a major global health challenge, particularly in low-resource regions. Approximately 88.1% of the 604,000 CC new cases occurred in low-and middle-income countries in 2020, and more than 90% of the 342,000 CC deaths occurred in low-and middle-income countries in 2020~1.

关键词： prevention Cervical epidemiology

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2024年

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian cancer Institute Linzhou cancer Hospital Center for Disease control and Prevention of Sheyang County department of cancer Prevention and control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Luoshan Center for Disease control and Prevention Office for cancer control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer(GC) in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates(CIRs) of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic(atrophic gastritis/intestinal metaplasia) and neoplastic lesions(low-grade/high-grade dysplasia), respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients(≥3 risk factors) with non-neoplastic lesions showed higher GC risks(adjusted HR=7.73, 95%CI: 4.29–13.92), and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions(aHR=3.07, 95%CI: 1.67–5.64) and high-risk patients with mild lesions(aHR=7.29, 95%CI: 3.58–14.86) showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway

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Current Medical Science 2024年第1期44卷 93-101页

作者： Li-wei ZHANG Hong-qi FENG Song-bo FU Dian-jun SUN Center for Endemic Disease control Chinese Center for Disease Control and PreventionHarbin Medical UniversityNHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University)Key Lab of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceHarbin 150086China

Objective Keshan disease(KD)is a myocardial mitochondrial disease closely related to insufficient selenium(Se)and protein *** induced putative kinase 1(PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the *** study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial *** A low Se and low protein animal model was *** hundred Wistar rats were randomly divided into 5 groups(control group,low Se group,low protein group,low Se+low protein group,and corn from KD area group).The JC-1 method was used to detect the mitochondrial membrane potential(MMP).ELISA was used to detect serum creatine kinase MB(CK-MB),cardiac troponin I(cTnI),and mitochondrial-glutamicoxalacetic transaminase(M-GOT)***-PCR and Western blot analysis were used to detect the expression of PINK1,Parkin,sequestome 1(P62),and microtubule-associated proteins1A/1B light chain 3B(MAP1LC3B).Results The MMP was significantly decreased and the activity of CK-MB,cTnI,and M-GOT significantly increased in each experimental group(low Se group,low protein group,low Se+low protein group and corn from KD area group)compared with the control group(Pcontrol group(P<0.05 for all).Conclusion Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

关键词： Keshan disease low selenium and low protein myocardial mitochondrial injury PTEN induced putative kinase 1(PINK1)/Parkin mitochondrial autophagy

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