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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

Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression

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World Journal of Gastroenterology 2014年第28期20卷 9392-9404页

作者： Ying-Yi Li Naofumi Mukaida cancer research Institute Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical CollegeFudan University Division of Molecular Bioregulation Cancer Microenvironment Research ProgramCancer Research InstituteKanazawa University

Pim-3 is a member of the provirus integration site for Moloney murine leukemia virus(Pim)family proteins that exhibit serine/threonine kinase *** to the other Pim kinases(Pim-1 and Pim-2),Pim-3 is involved in many cellular processes,including cell proliferation,survival,and protein *** Pim-3is expressed in normal vital organs,it is overexpressed particularly in tumor tissues of endoderm-derived organs,including the liver,pancreas,and *** of Pim-3 expression can retard in vitro cell proliferation of hepatocellular,pancreatic,and colon carcinoma cell lines by promoting cell ***-3 lacks the regulatory domains similarly as Pim-1 and Pim-2 lack,and therefore,Pim-3 can exhibit its kinase activity once it is ***-3 expression is regulated at transcriptional and post-transcriptional levels by transcription factors(e.g.,Ets-1)and post-translational modifiers(e.g.,translationally-controlled tumor protein),***-3 could promote growth and angiogenesis of human pancreatic cancer cells in vivo in an orthotopic nude mouse ***,a Pim-3 kinase inhibitor inhibited cell proliferation when human pancreatic cancer cells were injected into nude mice,without inducing any major adverse ***,Pim-3 kinase may serve as a novel molecular target for developing targeting drugs against pancreatic and other types of cancer.

关键词： Serine/threonine kinase Pancreatic cancer Ets-1 Translationally controlled tumor protein c-Myc Vascular endothelium growth factor Apoptosis Cell cycle

Oral cancer incidence and mortality in China, 2011

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Chinese Journal of cancer research 2015年第1期27卷 44-51页

作者： Shao-Kai Zhang Rongshou Zheng Qiong Chen Siwei Zhang Xibin Sun Wanqing Chen Department of cancer epidemiology Henan Cancer Hospital/Institute Affiliated cancer Hospital of Zhengzhou University National Central cancer Registry National Cancer Center

Objective： To descript the incidence and mortality rates of oral cancer among Chinese population in 2011, and provide valuable data for oral cancer prevention and research. Methods： Data from 177 population-based cancer registries distributed in 28 provinces were accepted for this study after evaluation based on quality control criteria, covering a total of 175,310,169 populations and accounting for 13.01% of the overall national population in 2011. Incidence and mortality rates were calculated by area, gender and age groups. The numbers of new cases and deaths were estimated using the 5-year age-specific cancer incidence/mortality rates and the corresponding populations. The Chinese population in 2000 and World Segi＇s population were used for age-standardized rates. Results： The estimate of new cases diagnosed with oral cancer was 39,450 including 26,160 males and 13,290 females. The overall crude incidence rate for oral cancer was 2.93/100,000. The age-standardized rates by China （ASRcN） population and by World population （ASRwld） were 2.22/100,000 and 2.17/100,000, respectively. Among subjects aged 0-74 years, the cumulative incidence rate was 0.25%. The estimated number of oral cancer deaths of China in 2011 was 16,933, including 11,794 males and 5,139 females. The overall crude mortality rate was 1.26/I00,000, accounting for 0.80% of all cancer deaths. The ASRcN and ASP^Id for mortality were 0.90/100,000 and 0.89/100,000, respectively. Among subjects aged 0-74 years, the cumulative mortality rate was 0.10%. The incidence and mortality rates of oral cancer were much higher in males and urban areas than in females and rural areas. In addition, the incidence and mortality rates were increased by the raising of ages. Conclusions： Results in the study may have important roles for oral cancer prevention and research. Although oral cancer burden of China is not high, we must pay attention to this malignancy as well. In addition, further researches need to be done for

关键词： Incidence mortality oral cancer China

Global burden of thyroid cancer in 2022: Incidence and mortality estimates from GLOBOCAN

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中华医学杂志(英文版) 2024年第21期137卷 2567-2576页

作者： Lyu Zhangyan Zhang Yu Sheng Chao Huang Yubei Zhang Qiang Chen Kexin 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 Tianjin China Department of Maxillofacial and Otorhinolaryngology Oncology National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital Tianjin China

Background: Thyroid cancer (TC) is the most common malignancy of the endocrine system. This study aimed to assess the global distribution of TC incidence and mortality in 2022, as well as to predict the burden for the year ***: Data from the GLOBOCAN 2022 database were used to analyze the age-standardized incidence and mortality rates of TC by sex, age group (cancer worldwide with disparities across regions, genders, and age groups. Our results provide light on the worldwide TC disease burden and facilitate regionally customized prevention measures.

关键词： Thyroid cancer Incidence Mortality Trend analysis GLOBOCAN 2022

Meta-Analysis of the Association between Mir-196a-2 Polymorphism and cancer Susceptibility

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Clinical oncology and cancer researeh 2012年第1期9卷 63-72页

作者： Huan Zhang Yu-liang Su Herbert Yu Bi-yun Qian Department of epidemiology and Biostatistics Tianjin Medical University Cancer Institute and Hospital Key Laboratory of cancer Prevention and Therapy Tianjin Medical UniversityMinistry of Education epidemiology program University of Hawaii Cancer CenterHonolulu 96813HIUSA

Objective MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis. The miR- 196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility. This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. Methods A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism. Results A significant association was found between rs11614913 polymorphism and cancer risk in four genetic models （CT vs. TT, OR-1.15, 95%CI=1.05-1.27; CC vs. TT, OR=1.23, 95%CI=1.08-1.39; Dominant model, OR=1.17, 95%CI=1.06-1.30; Additive model, OR-1.08, 95%CI=1.01-1.14）. In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectat cancer, but not with liver, gastric, or esophageal cancer. In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup. Conclusions The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations.

关键词： MIRN196 microRNA human polymorphism neoplasms meta-analysis

Human papilloma virus and esophageal carcinoma in a Latin-American region

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World Journal of Gastroenterology 2009年第25期15卷 3142-3147页

作者： Roberto Herrera-Goepfert Marcela Lizano Suminori Akiba Adela Carrillo-García Mauricio Becker-D'Acosta Department of Pathology National Cancer Institute Unit of Biomedical research in cancer National Cancer Institute and Biomedical Research InstituteNational Autonomous University of Mexico Department of epidemiology and Preventive Medicine Kagoshima University Graduate School of Medical and Dental Sciences

AIM:To investigate the presence of high-risk human papilloma virus (HPV) in esophageal squamous cell carcinomas (ESCCs) in a non-selected Mexican ***: Cases with a pathological diagnosis of squamous cell carcinoma of the esophagus were obtained from Department of Pathology files, at the National cancer Institute in Mexico City during the period between 2000 and 2008. Slides from each case were reviewed and cases with sufficient neoplastic tissue were selected for molecular analysis. DNA was extracted from paraffin-embedded tissue samples for polymerase chain reaction analysis to detect HPV DNA sequences. Demographic and clinical data of each patient were retrieved from corresponding clinical ***: HPV was detected in 15 (25%) of ESCCs. HPV-16 was the most frequently observed genotype, followed by HPV-18; HPV-59 was also detected in one case. Unfortunately, HPV genotype could not be established in three cases due to lack of material for direct sequencing, although universal primers detected the presence of HPV generic sequences. No low-risk HPV genotypes were found nor was HPV-16/18 co-infection. HPV presence in ESCC was not significantly associated with gender, age, alcohol consumption, smoking, anatomic location, or histologic grade. All patients belonged to low and very low socioeconomic strata, and were diagnosed at advanced disease stage. Male patients were most commonly affected and the male:female ratio in HPV-positive ESCC increased two- fold in comparison with HPV-negative cases (6.5:1 vs 3.1:1).CONCLUSION: High prevalence of high-risk HPV in ESCC in Mexico does not support the hypothesis that HPV-associated ESCC is more common in areas with higher ESCC incidence rates.

关键词： Esophagus Squamous cell carcinoma virusHuman papilloma virus High-risk human papilloma virus

Effect of dietary vitamin C on gastric cancer risk in the Korean population

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World Journal of Gastroenterology 2016年第27期22卷 6257-6267页

作者： Bach Viet Hoang Jeonghee Lee Il Ju Choi Young-Woo Kim Keun Won Ryu Jeongseon Kim Department of cancer Control and Policy Graduate School of Cancer Science and Policy National Cancer Center Molecular epidemiology Branch Research Institute National Cancer Center Center for Gastric cancer National Cancer Center Hospital National Cancer Center

AIM: To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer ***: Our study included 830 control subjects and 415 patients. Data regarding demographics, medical history, and lifestyle, including dietary and nutrient intake, were collected using reliable selfadministered questionnaires. Dietary intake information was collected from the participants using a food frequency questionnaire that has been previously reported as reliable and valid. A rapid urease test and a histological evaluation were used to determine the presence of Helicobacter pylori(H. pylori) infection. Twenty-three vitamin C-contributing foods were selected, representing over 80% of the cumulative vitamin C contribution. RESULTS: In analyses adjusted for first-degree family history of gastric cancer, education level, job, household income, smoking status, and regular exercise, an inverseassociation between vitamin C intake and gastric cancer risk was observed for the highest(≥ 120.67 mg/d) vs the lowest(cancer incidence was found in either men or women infected with H. pylori. Vitamin C-contributing foods, including cabbage [0.45(0.32-0.63), 0.50(0.34-0.75), 0.45(0.25-0.81)], strawberries [0.56(0.40-0.78), 0.49(0.32-0.74), 0.52(0.29-0.93)], and bananas [0.40(0.29-0.57), 0.41(0.27-0.62), 0.34(0.19-0.63)], were protective factors against the risk of gastric cancer based on the results of the overall adjusted analyses and the results for men and women, ***: A protective effect of vitamin C and vitamin C-contributing foods against gastric cancer was observed. Further studies using larger sample sizes are required to replicate our results.

关键词： Vitamin C Vitamin C-contributing foods Helicobacter pylori Gastric cancer Korean population

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael S.Wolfe Computational Medicine program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

The efficacies and biomarker investigations of antiprogrammed death-1 (anti-PD-1)-based therapies for metastatic bone and soft tissue sarcoma

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cancer Biology & Medicine 2022年第6期19卷 910-930页

作者： Jia Lu Ting Li Zhichao Liao Hui Yu Yongtian Zhao Haixiao Wu Zhiwu Ren Jun Zhao Ruwei Xing Sheng Teng Yun Yang Xiangchun Li Kexin Chen Jonathan Trent Jilong Yang 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 CancerTianjin 300060China Department of Infection Management Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Key Laboratory of Molecular cancer epidemiology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China YuceBio Technology Co. Ltd.Shenzhen 518172China Department of epidemiology and Biostatistics Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Sarcoma Multidisciplinary program Sylvester Comprehensive Cancer CenterThe University of MiamiMiamiFL 33136USA

Objective:Sarcomas are a group of rare malignancies with various *** with metastatic sarcoma who have failed traditional treatments can possibly achieve better prognoses from using novel therapies,including anti-programmed death-1(PD-1)-based ***:We retrospectively analyzed clinical data of 24 metastatic sarcoma patients from June 15,2016 to December 30,*** patients mainly received angiogenesis inhibitors combined with anti-PD-1 therapy after they became resistant to traditional ***,8 patients underwent panel DNA and whole transcript ***:Six patients received 2 cycles of anti-PD-1 therapy and were included in the safety evaluation only *** median follow-up time was 5.77 *** median progression-free survival was 7.59 months,the overall response rate was 16.7%and the disease control rate was 55.6%.Based on whole exome and transcript sequencing data,there was no association between TMB,TNB,MSI,HLA-LOH,and PD-L1 expressions and sarcoma types with clinical *** efficacy and bioinformatics analyses indicated higher intratumoral heterogeneity(ITH)in progressive disease(PD)patients and lower ITH in partial response(PR)and stable disease patients.A higher percentage of immune cell infiltration,especially monocytes,was observed in PR *** stromal gene expression was increased in PD patients but decreased in PR *** analysis revealed that an increased TGF-βsignaling pathway was reversely correlated with anti-PD-1 efficacy,while a decreased inflammatory response signaling pathway was positively correlated with anti-PD-1 ***:Our study showed PD-1 inhibitors combined with anti-angiogenesis agents were effective and ***,monocyte ratio,stroma subtypes,and the status of immune-associated signaling pathways may be related with anti-PD-1 based therapy.

关键词： Sarcoma PD-1 PD-L1 immunotherapy angiogenesis safety efficacy biomarker