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Weight change and all-cause and cause-specific mortality:A 25-year follow-up study

Chinese Medical Journal 2024年第10期137卷 1169-1178页

作者： Huan Yang Jianbing Wang Xiaokun Wang Wanyi Sun Chenyunhao Tong Jinhu Fan Youlin Qiao Christian *** 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 Department of Public Health Zhejiang University School of MedicineNational Clinical Research Center for Children’s HealthHangzhouZhejiang 310058China Metabolic epidemiology Branch Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleMD 20850USA

Background:Whether the dynamic weight change is an independent risk factor for mortality remains *** study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial(NIT)***:Body weight of 21,028 healthy residents of Linxian,Henan province,aged 40-69 years was measured two times from 1986 to *** events were prospectively collected up to *** maintenance group(weight changecancer(HR_(cancer)=1.12,95%CI:1.03-1.21,P=0.009),and heart disease(HR_(Heart diseases)=1.21,95%CI:1.11-1.31,Pcancer)=0.89,95%CI:0.79-0.99,P=0.033)lower risk of cancer mortality and 23%higher risk of stroke mortality(HR_(Stroke)=1.23,95%CI:1.12-1.34,Pcancer death(HR_(Overweight to normal)=1.20,95%CI:1.04-1.39;HR_(Becoming underweight)=1.44,95%CI:1.24-1.67),while stable overweight could increase the risk of total death(HR_(Stable overweight)=1.11,95%CI:1.05-1.17)and death from stroke(HR_(Stable overweight)=1.44,95%CI:1.33-1.56).Interaction effects were observed between age and weight change on cancer mortality,as well as between baseline BMI and weight change on all-cause,heart disease,and stroke mortality(all P_(

关键词： Weight change All-cause mortality cancer Stroke Heart diseases Body mass index

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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 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 Epidemiology Key Laboratory of Prevention and Control of Human Major Diseases Ministry of Education National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin Medical University

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 incidence mortality polygenic risk score screening

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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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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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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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Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia

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Chinese Medical Journal 2024年第8期137卷 980-989页

作者： Zhiyuan Fan Jing Zhou Yuan Tian Yu Qin Zhaojun Liu Liankun Gu Sanford M.Dawsey Wenqiang Wei Dajun Deng National Central cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Carcinogenesis and Translational Research(MOE/Beijing) Division of EtiologyPeking University Cancer Hospital and InstituteBeijing 100142China Division of cancer epidemiology and Genetics National Cancer InstituteBethesdaMDUSA Collaborative Innovation Center for cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsu 211166China

Background:Somatic copy number variations(SCNVs)in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell ***,whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia(ESCdys)is *** study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate(m/M)***:This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China(Ci County,Hebei Province;Yanting,Sichuan Province;Linzhou,Henan Province;Yangzhong,Jiangsu Province;and Feicheng,Shandong Province)from 2005 to *** DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients,and a quantitative polymerase chain reaction assay,P16-Light,was used to detect CDKN2A copy *** cumulative regression and progression rates of ESCdys were evaluated using competing risk ***:A total of 205 patients with baseline m/M ESCdys were *** proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts(18.8%[13/69]vs.35.0%[28/80]vs.51.8%[29/56],P<0.001).In the univariable competing risk analysis,the cumulative regression rate was statistically significantly lower(P=0.008),while the cumulative progression rate was higher(P=0.017)in ESCdys patients with CDKN2A deletion than in those without CDKN2A ***2A deletion was also an independent predictor of prognosis in ESCdys(P=0.004)in the multivariable ***:The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

关键词： Somatic copy number variations Esophageal squamous cell carcinoma Esophageal neoplasms Squamous intraepithelial lesions DNA copy number variations Prognosis Prospective study

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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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EZH2 is a prognostic factor associated with tumor stemness and immune infiltration in skull base chordoma

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Genes & Diseases 2024年第5期11卷 85-87页

作者： Qian Liu Mingxuan Li Yujia Xiong Yutao Shen Tianshun Ma Tianhao Zhang Xiaohong R.Yang Yazhuo Zhang Jiwei Bai Beijing Neurosurgical Institute Capital Medical UniversityBeijing 100070China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Division of cancer epidemiology and Genetics National Cancer InstituteNIHDHHSBethesdaMD 20892USA

Enhancer of zeste homolog 2(EZH2),an epigenetic regulator that inhibits transcription primarily through trimethylation of Lys-27 in histone 3(H3K27me3),has been reported to play an important role in the regulation of cell cycle,autophagy,and apoptosis,and DNA damage repair.1 EZH2 is highly expressed in a variety of cancers including prostate cancer,breast cancer,and renal clear cell carcinoma,and is associated with adverse prognosis.1 Moreover,it has been reported that EZH2 might increase tumor stemness and metastasis capacity and inhibit antitumor immunity by affecting T cells,NK cells,macrophages,and immune checkpoints.2,3 However,the prognostic value and the mechanism of EZH2 have not been investigated in *** this study,RNA sequencing and whole genome sequencing data based on 48 skull base chordomas as well as immunohistochemistry of paraffin sections were analyzed to elucidate the role of EZH2 in skull base *** found copy number gain mediated high EZH2 expression is associated with tumor stemness,M2 macrophage infiltration,and adverse prognosis in ***,we demonstrated that EZH2 promotes the proliferation,migration,and invasion of chordoma cells in in vitro cell experiments.

关键词： EZH2 immunity invasion

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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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Reliability of a computerized system for strabismus screening

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 126-130页

作者： Supaporn Tengtrisorn Alan Frederick Geater Department of Ophthalmology Faculty of MedicinePrince of Songkla UniversityHat-YaiSongkla 90110Thailand epidemiology unit Faculty of MedicinePrince of Songkla UniversityHat-YaiSongkla 90110Thailand

AIM:To evaluate the reliability of Photo-Hirschberg screening for global strabismus performed by non-specialized ***:Participants at three sites were *** person at each site was trained in visual acuity measurement and use of the computerized *** acuity was measured,and strabismus testing was performed using two flash *** data from the three primary observers were sent to an experienced assistant researcher,who was blinded to the primary results,for *** primary and re-evaluation results of the Photo-Hirschberg screenings using weighted kappa for agreement were ***:The study included 181 participants(88 males and 93 females)and the results for primary and re-evaluation screenings were *** participants with contrasting results presented with unclear corneal light *** and specificity were 100%[95%confidence interval(CI):29.0%-100%]and 99.4%(95%CI:96.6%-100%),respectively,based on the Agresti test of the primary evaluation,considering the re-evaluated classification as ***:The computerized system can be used for primary strabismus screening by non-specialized personnel,with 98.8%agreement with ***,it cannot be used as a substitute for professional examination.

关键词： strabismus screening computerized system Photo-Hirschberg screening

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