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Development and evaluation of the screening performance of a low-cost high-risk screening strategy for breast cancer

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cancer Biology & Medicine 2022年第9期19卷 1375-1384页

作者： Yubei Huang Huan Wang Zhangyan Lyu Hongji Dai Peifang Liu Ying Zhu Fengju Song Kexin Chen Department of Cancer Epidemiology and Biostatistics 2Department of Breast ImagingTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Molecular Epidemiology of TianjinKey Laboratory of Breast Cancer Prevention and TherapyMinistry of EducationTianjin 300060China

Objective:To develop and evaluate the screening performance of a low-cost high-risk screening strategy for breast cancer in low resource areas.Methods:Based on the Multi-modality Independent Screening Trial,6 questionnaire-based risk factors of breast cancer(age at menarche,age at menopause,age at first live birth,oral contraceptive,obesity,family history of breast cancer)were used to determine the women with high risk of breast cancer.The screening performance of clinical breast examination(CBE),breast ultrasonography(BUS),and mammography(MAM)were calculated and compared to determine the optimal screening method for these high risk women.Results:A total of 94 breast cancers were detected among 31,720 asymptomatic Chinese women aged 45–65 years.Due to significantly higher detection rates(DRs)and suitable coverage of the population,high risk women were defined as those with any of 6 risk factors.Among high risk women,the DR for BUS[3.09/1,000(33/10,694)]was similar to that for MAM[3.18/1,000(34/10,696)],while it was significantly higher than that for the CBE[1.73/1,000(19/10,959),P=0.002].Compared with MAM,BUS showed significantly higher specificity[98.64%(10,501/10,646)vs.98.06%(10,443/10,650),P=0.001],but no significant differences in sensitivity[68.75%(33/48)vs.73.91%(34/46)],positive prediction values[18.54%(33/178)vs.14.11%(34/241)],and negative prediction values[99.86%(10,501/10,516)vs.99.89%(10,443/10,455)].Further analyses showed no significant difference in the percentages of early stage breast cancer[53.57%(15/28)vs.50.00%(15/30)],lymph node involvement[22.73%(5/22)vs.28.00%(7/25)],and tumor size≥2 cm[37.04%(10/27)vs.29.03%(9/31)]between BUS and MAM.Subgroup analyses stratified by breast densities or age at enrollment showed similar results.Conclusions:The low-cost high-risk screening strategy based on 6 questionnaire-based risk factors was an easy-to-use method to identify women with high risk of breast cancer.Moreover,BUS and MAM had comparable screening performances among high risk women.

关键词： cancer screening breast cancer high risk mammography ultrasonography

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Trends in mortality of liver disease due to hepatitis B in China from 1990 to 2019: findings from the Global Burden of Disease Study

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Chinese Medical Journal 2022年第17期135卷 2049-2055页

作者： Guiying Cao Jue Liu Min Liu department of epidemiology and biostatistics School of Public HealthPeking UniversityBejing 100191China

Background::Hepatitis B is a viral infection that attacks the liver and can cause both potentially life-threatening acute and chronic liver disease.China has the world’s largest burden of hepatitis B and is considered to be a major contributor toward the goal of World Health Organization(WHO)of eliminating hepatitis B virus(HBV)as a global health threat by 2030.This study aimed to analyze data from the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)to determine the trends in mortality of liver disease due to hepatitis B in China between 1990 and 2019 and the gap with the WHO’s goal.Methods::Annual deaths and age-standardized mortality rates(ASMRs)of liver disease due to hepatitis B in China between 1990 and 2019 were collected from GBD 2019.We calculated the percentage changes in deaths and estimated annual percentage changes(EAPCs)of ASMRs of liver disease due to hepatitis B.Results::In China,deaths of total liver disease due to hepatitis B decreased by 29.13%from 229 thousand in 2016 to 162 thousand in 2019,and ASMR decreased by an average of 4.92%(95%confidence interval[CI]:4.45–5.39%)per year in this period.For the spectrum of liver disease due to hepatitis B,deaths decreased by 74.83%,34.71%,and 23.34%for acute hepatitis,cirrhosis and other chronic liver diseases,and liver cancer from 1990 to 2019,respectively,and ASMRs of acute hepatitis(EAPC=–7.63;95%CI:–8.25,–7.00),cirrhosis and other chronic liver diseases(EAPC=–4.15;95%CI:–4.66,–3.65),and liver cancer(EAPC=–5.17;95%CI:–6.00,–4.33)decreased between 1990 and 2019.The proportions of older adults aged≥70 years among all deaths of the spectrum of liver disease due to hepatitis B increased from 1990 to 2019.Deaths of liver cancer due to hepatitis B increased by 7.05%from 2015 to 2019.Conclusions::Although a favorable trend in the mortality of liver disease due to hepatitis B was observed between 1990 and 2019,China still faces challenges in achieving the WHO’s goal of eliminating HBV as a public threat by 2030.Therefore,efforts to increase the

关键词： Hepatitis B Acute hepatitis B Chronic liver disease Liver cirrhosis Liver neoplasms Global Burden of Disease Global Health China

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Global Trends and Regional Differences in Hepatitis C Virus Infection Prevalence and Implications for Prevention--Worldwide,1990−2017

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China CDC weekly 2020年第30期2卷 564-569,I0001-I0004页

作者： Wenzhan Jing Jue Liu Min Liu department of epidemiology and biostatistics School of Public HealthPeking UniversityBeijingChina

What is already known on this topic?The global prevalence of hepatitis C virus(HCV)infection in 2015 has been modeled to assess the disease burden in 21 Global Burden of Disease(GBD)regions.However,there is no study to clarify the global long-term trends and regional differences in HCV infection prevalence.What is added by this report?This report clarified the global temporal trends and regional differences in HCV infection prevalence.Global HCV infection age-standardized prevalence rate(ASR)gradually decreased from 1990 to 2017 except in Eastern Europe,and liver cancer due to hepatitis C ASR increased worldwide with drastic shifts in lowmiddle Socio-Demographic Index(SDI)regions in the last decade.What are the implications for public health practice?HCV is still prevalent worldwide despite the development of highly effective direct-acting antivirals(DAAs)and showed a reemergence concurrent with the opioid crisis.HCV infection prevention might involve at least 3 aspects:first,prohibiting HCV widespread transmission among general populations;second,increasing global DAAs coverage;and third,continuously investing in the development of the HCV vaccine.

关键词： prevalence prevention Eastern

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福清市农村居民对新型冠状病毒疫情及预防认知的调查研究

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International Journal of Nursing Sciences 2022年第2期9卷 196-202,I0006页

作者：刘晓君杜珊珊冯瑞梅鄢灵君黄毅敏叶为民 department of Health Management School of Public HealthFujian Medical UniversityFuzhouChina department of epidemiology and Health Statistics&Key Laboratory of Ministry of Education for Gastrointestinal cancer Fujian Medical UniversityFuzhouChina department of Medical epidemiology and biostatistics Karolinska InstitutetStockholmSweden

目的了解福清市农村居民对新型冠状病毒疫情及自我防护的认知情况。方法本研究为横断面研究,采用自行设计的新型冠状病毒疫情及自我防护认知问卷,2020年5—6月共调查福清市农村1426名18岁以上常住居民。采用二元logistic回归模型鉴别新... 详细信息

目的了解福清市农村居民对新型冠状病毒疫情及自我防护的认知情况。方法本研究为横断面研究,采用自行设计的新型冠状病毒疫情及自我防护认知问卷,2020年5—6月共调查福清市农村1426名18岁以上常住居民。采用二元logistic回归模型鉴别新型冠状病毒疫情及其预防不同认知水平居民的主要社会人口学特征。结果福清市农村居民对新型冠状病毒疫情认知的平均得分和中位数得分分别为5.53分和6分;对新型冠状病毒疫情自我保护知识的平均得分和中位数得分分别为10.34分和11分。二元Logistic回归模型显示,年长人群(Adjusted OR 45~59=2.26,95%CI=1.20~4.27;Adjusted OR 60~69=3.13,95%CI=1.63~5.98;Adjusted OR≥70=4.68,95%CI=2.35~9.33)对新型冠状病毒疫情的了解更为缺乏;受教育程度、家庭平均年收入较高的人群对新型冠状病毒疫情的认知水平和相关自我防护知识水平均较高(P<0.05);单身、离异或丧偶人群(Adjusted OR=1.67,95%CI=1.13~2.46)更缺乏对新型冠状病毒疫情自我保护的知识。结论研究表明,福清市农村居民对新型冠状病毒疫情认知水平一般,但相关自我保护知识水平较高。研究建议在面对类似新冠这类重大疫情时,对居民实施相关自我防护知识的宣传教育或更为重要,尤其要加强对无配偶、年龄较大、受教育水平和/或收入较低的重点人群进行自我防范措施的宣传教育。

关键词：新型冠状病毒疫情知识疾病流行农村居民自我防护问卷调查

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Associations between cancer family history and esophageal cancer and precancerous lesions in high-risk areas of China

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Chinese Medical Journal 2022年第7期135卷 813-819页

作者： Jiachen Zhou Kexin Sun Shaoming Wang Ru Chen Minjuan Li Jianhua Gu Zhiyuan Fan Guihua Zhuang Wenqiang Wei department of epidemiology and biostatistics School of Public HealthXl’an Jiaotong University Health Science CenterXi’anShaanxi 710061China 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

Background:Family clustering of esophageal cancer(EC)has been found in high-risk areas of China.However,the relationships between cancer family history and esophageal cancer and precancerous lesions(ECPL)have not been comprehensively reported in recent years.This study aimed to provide evidence for identification of high-risk populations.Methods:This study was conducted in five high-risk areas in China from 2017 to 2019,based on the National Cohort of Esophageal cancer.The permanent residents aged 40 to 69 years were examined by endoscopy,and pathological examination was performed for suspicious lesions.Information on demographic characteristics,environmental factors,and cancer family history was collected.Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL.Results:Among 33,008 participants,6143(18.61%)reported positive family history of EC.The proportion of positive family history varied significantly among high-risk areas.After adjusting for risk factors,participants with a family history of positive cancer,gastric and esophageal cancer or EC had 1.49-fold(95%confidence interval[CI]:1.36-1.62),1.52-fold(95%CI:1.38-1.67),or 1.66-fold(95%CI:1.50-1.84)higher risks of ECPL,respectively.Participants with single or multiple first-degree relatives(FDR)of positive EC history had 1.65-fold(95%CI:1.47-1.84)or 1.93-fold(95%CI:1.46-2.54)higher risks of ECPL.Participants with FDRs who developed EC before 35,45,and 50 years of age had 4.05-fold(95%CI:1.30-12.65),2.11-fold(95%CI:1.37-3.25),and 1.91-fold(95%CI:1.44-2.54)higher risks of ECPL,respectively.Conclusions:Participants with positive family history of EC had significantly higher risk of ECPL.This risk increased with the number of EC positive FDRs and EC family history of early onset.Distinctive genetic risk factors of the population in high-risk areas of China require further investigation.Trial registration:ChiCTR-EOC-17010553.

关键词： Esophageal cancer Family history High-risk area Cross-sectional study

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Systematic analysis on expression quantitative trait loci identifies a novel regulatory variant in ring finger and WD repeat domain 3 associated with prognosis of pancreatic cancer

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Chinese Medical Journal 2022年第11期135卷 1348-1357页

作者： Ying Zhu Xiating Peng Xiaoyang Wang Pingting Ying Haoxue Wang Bin Li Yue Li Ming Zhang Yimin Cai Zequn Lu Siyuan Niu Nan Yang Rong Zhong Jianbo Tian Jiang Chang Xiaoping Miao department of epidemiology and biostatistics School of Public HealthWuhan UniversityWuhanHubei 430072China department of epidemiology and biostatistics Key Laboratory for Environment and HealthSchool of Public HealthTongji Medical CollegeHuazhong University of Sciences and TechnologyWuhanHubei 430030China.

Background:Pancreatic adenocarcinoma(PAAD)is an extremely lethal malignancy.Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging.Previously identified prognostic genes from several expression profile analyses were inconsistent.The regulatory genetic variants that affect PAAD prognosis were largely unknown.Methods:Firstly,a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD.Next,to identify the regulatory variants for those candidate genes,expression quantitative trait loci analysis was implemented with PAAD data resources from The cancer Genome Atlas.Then,a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus.Finally,a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.Results:A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis.Fourteen regulatory loci in 12 of the 128 genes were discovered,among which,only rs4887783,the functional variant in the promoter of Ring Finger and WD Repeat Domain 3(RFWD3),presented significant association with PAAD prognosis in both stages of the population study.Dualluciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele,which predicts the worse prognosis,enhanced the binding of transcript factor REST,thus elevating RFWD3 expression.Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate.RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process.Conclusions:RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.

关键词： Pancreatic cancer Survival RFWD3 Genetic variation Quantitative trait loci

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MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression

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Chinese Journal of cancer 2016年第12期35卷 666-672页

作者： Run-Fen Cheng Jian Wang Jing-Yi Zhang Lin Sun Yan-Rui Zhao Zhi-Qiang Qiu Bao-Cun Sun Yan Sun department of Pathology Tianjin Medical University Cancer Institute and Hospital department of Pancreatic Oncology Tianjin Medical University Cancer Institute and Hospital department of epidemiology and biostatistics Tianjin Medical University Cancer Institute and Hospital department of Pathology Tianjin Medical University

Background: MicroRNA?506(miR?506) has been reported to function in several tumors as a tumor suppressor gene or oncogene. However, the expression and role of miR?506 in pancreatic ductal adenocarcinoma(PDAC) remains unclear. In this study, we aimed to evaluate the phenotype of miR?506 in PDAC.Methods: Using mi RNA in situ hybridization, we examined the expression of miR?506 in 113 PDACs and 87 paired normal pancreatic tissues. We evaluated mi R?506 expression in PDAC cells, normal pancreatic ducts, and acinus/islands, and we analyzed the associations between miR?506 expression and the clinicopathologic characteristics of PDAC patients.Results: miR?506 expression was higher in PDAC than in matched normal pancreatic ductal cells(P < 0.001). On the other hand, the combined group of well and moderately diferentiated PDACs showed higher levels of mi R?506 than the poorly diferentiated ones(P = 0.023). Moreover, mi R?506 expression was negatively associated with pathologic T category(P = 0.004) and lymph node metastasis(P = 0.033), suggesting that mi R?506 might inhibit the progression of PDAC.Conclusions: Our results suggest that mi R?506 either plays a role as an oncogene in the tumorigenesis and a tumor suppressor in the progression or serves as a house?keeping, tumor?suppressing mi RNA, whose expression can be activated by oncogenic signals in early development to hinder the progression of PDAC.

关键词： Pancreatic ductal adenocarcinoma miR?506 Tumor suppressor Development Progression

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An exploration for quantification of overdiagnosis and its effect for breast cancer screening

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Chinese Journal of cancer Research 2020年第1期32卷 26-35页

作者： Lei Yang Shengfeng Wang Yubei Huang Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Beijing Office for Cancer Prevention and ControlPeking University Cancer Hospital&InstituteBeijing 100142China department of epidemiology&biostatistics School of Public HealthPeking UniversityBeijing 100191China department of epidemiology and biostatistics Key Laboratory of Cancer Prevention and TherapyTianjinKey Laboratory of Breast Cancer Prevention and TherapyMinistry of EducationNational Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

Objective: To redefine overdiagnosis and reestimate the proportion of overdiagnosis of breast cancer caused by screening based on the Surveillance, epidemiology, and End Results(SEER, 1973-2015) Program data.Methods: The breast cancer diagnosed before 1977 was defined as the no-screening cohort since America had initiated breast cancer screening from 1977. The breast cancer diagnosed in 1999 was defined as the screening cohort due to no increases in both the proportion of early-stage breast cancer until 1999 and the overall survival of early-stage breast cancer diagnosed over the three years since 1999. The magnitude of overdiagnosis was calculated as the difference in the proportions of early-stage breast cancer patients with long-time(15-year) survival to all breast cancer patients between two cohorts.Results: Over 23 years before and after widespread screening in America, the proportion of early-stage breast cancer patients increased from 52.1%(16,891/32,443) to 72.7%(16,021/22,025)(Pcancer patients increased from 51.1% to 61.5%(Pcancer patients with long-time survival to all breast cancer patients increased from 26.6%(52.1%×51.1%) to 44.7%(72.7%×61.5%). Assuming no improvements in cancer screening technology and treatment technology, 18.1%(44.7%-26.6%) of breast cancer patients were overdiagnosed associated with screening. The age-specific overdiagnosis rates were 18.9%, 24.7%, 24.5%, 20.5%, and 8.3% for breast cancer patients aged 40-49, 50-59, 60-69, 70-74, and ≥75 years old, respectively.Conclusions: Overdiagnosis caused by mammographic screening is probably overestimated in current screening practices. Further trials with more sophisticated designs and analyses are needed to validate our findings in the future.

关键词： Breast cancer screening overdiagnosis

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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 understood.Here,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics data.As 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 CRC.Among the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in cancer.Our 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 signaling.Next,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 controls.Mechanistically,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 risk.In 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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预后因素研究中常见的统计错误--偏倚

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中国肺癌杂志 2014年第2期17卷 137-141页

作者：付浩中国胸腺瘤协作组全体成员 Mithat G?nen 北京大学肿瘤医院 department of epidemiology and biostatistics Memorial Sloan-Kettering Cancer Center

预后因素是患者诊治中非常重要的内容，大多数肿瘤患者的治疗决策取决于各种危险因素的存在与否。最突出的例子就是TNM（即肿瘤，淋巴结，远处转移）分期，但很多疾病都不能简单通过分期一个指标解决所有问题，而是要具体分析每个患者... 详细信息

预后因素是患者诊治中非常重要的内容，大多数肿瘤患者的治疗决策取决于各种危险因素的存在与否。最突出的例子就是TNM（即肿瘤，淋巴结，远处转移）分期，但很多疾病都不能简单通过分期一个指标解决所有问题，而是要具体分析每个患者的综合预后因素。目前在判断胸腺瘤预后的临床研究中，一个主要的困难是缺乏实践指南，以至于到底哪些是预后因素尚不明确。本文叙述了临床实践中的一些问题并指出了临床研究中存在的各种偏倚，并试图提供解决方案，其中有许多方面在其它文献中作了详细讨论，但忽视了偏倚的存在。

关键词：预后因素偏倚统计错误肿瘤患者临床研究危险因素远处转移实践指南

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