食管癌专病队列研究

项目来源

国家重点研发计划(NKRD)

项目主持人

魏文强

项目受资助机构

中国医学科学院肿瘤医院

立项年度

2016

立项时间

未公开

项目编号

2016YFC0901400

项目级别

国家级

研究期限

未知 / 未知

受资助金额

1835.00万元

学科

精准医学研究

学科代码

未公开

基金类别

精准医学研究重点专项

关键词

食管癌 ; 癌前病变 ; 高发区 ; 筛查 ; Esophageal cancer ; Precancerous lesions ; high risk areas ; screening

参与者

陈茹

参与机构

北京市肿瘤防治研究所;汕头大学医学院

项目标书摘要:本课题旨在依据统一的高发现场食管癌及其癌前病变人群队列建立标准规范,建立覆盖人群不少于10万人的前瞻性人群队列。收集人群流行病学基线调查信息、病理诊断信息和治疗随诊信息,采集血液、病变组织等生物样本,建立生物样品库和与之对应的数据信息库,为精准医学重大专项食管癌专病研究共享平台的搭建提供资源。目前,本课题已制定了9个高发区人群队列相关标准规范,出版了《上消化道癌筛查及早诊早治技术方案(2020年试行版)》,编制了《食管癌专病队列数据集》团体标准已正式送审。在8个高发区构建前瞻性队列121503人,收集队列人群的流行病学调查信息,同时收集内镜和病理诊断等诊断信息,并与调查信息进行链接。建成了以林州为中心样本库,磁县、扬中、肥城、盐亭、北肿和汕头为分中心的生物样本库。样本库建筑面积超过1200平方米,配备-80℃超低温冰箱28台,收集血液标本62808例,组织标本39041例,样本信息与流行病学调查信息以唯一编码相链接。在主动随访基础上,依托全国肿瘤登记中心平台,以二代身份证作为个体识别信息,在全国肿瘤登记系统中对队列人群的食管癌发病情况和人群生存情况进行追踪和调查,比对发病和死亡信息,完善随访数据,建立主动随访和被动随访相结合的高效动态随访体系,使随访率达到90%以上。建立食管癌专病队列研究项目数据管理平台,为食管癌防控研究提供了丰富的数据和样本资源。

Application Abstract: This project aims to establish standards for the cohort of esophageal cancer and its precancerous lesions in high-risk areas and establish a prospective cohort that covers a population of no less than 100,000.To collect epidemiological baseline survey information,pathological diagnosis information and treatment follow-up information,and to collect blood and tissue samples to establish a biobank with corresponding database.And to provide resources for the establishment of a shared platform for precision medicine of esophageal cancer research.At present,this project has formulated 9 standards related to esophageal cancer cohort in high-risk areas,published the"Upper Gastrointestinal Cancer Screening and Early Diagnosis and Treatment Technical Program(Trial Version in 2020)",and formulated the group standard of"Esophageal Cancer Special Disease Cohort Data Set"that has been formally submitted for review.This project constructed a prospective cohort of 121,503 subjects from 8 high risk areas,and collected their epidemiological survey information,as well as endoscopic diagnostic information and pathological diagnosis at the same time,and linked with each other.A biological sample bank with Linzhou as the center sample bank and Cixian,Yangzhong,Feicheng,Yanting,Beizhong and Shantou as the sub-centers has been established.The sample library has a building area of over 1,200 square meters,equipped with 28-80℃ ultra-low temperature refrigerators,collecting 62,808 blood samples and 39,041 tissue samples.The sample information and epidemiological survey information are linked with a unique code.On the basis of active follow-up,relying on the platform of the National Cancer Registry,using the second-generation ID card as individual identification information,the incidence death information was compared,and the survival of the cohort populations are tracked and investigated in the national cancer registry to improve the follow-up data,and to establish an efficient and dynamic follow-up system that combines active follow-up and passive follow-up,so that the follow-up rate can reach more than 90%.This project also establish a data management platform for esophageal cancer and provides a wealth of data and sample resources for esophageal cancer prevention and control research.

项目受资助省

北京市

项目实施周期(年)

5

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  • 1.A systematic review and meta-analysis on the relative and attributable risk of Helicobacter pylori infection and cardia and non-cardia gastric cancer

    • 关键词:
    • Gastric cancer; Helicobacter pylori; Meta-analysis; Prospective study;Population attributable fraction;SERUM PEPSINOGEN-I; FOLLOW-UP; CAGA; ASSOCIATION; IMMUNOBLOT;ADENOCARCINOMA; ERADICATION; ANTIBODIES; SEROPOSITIVITY; ESOPHAGEAL

    Introduction: This study aimed to update the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC).Methods: We searched PubMed, Embase, and Cochrane Library from 1990 to December 2021 to identify prospective studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and GC.Results: Including 27 studies, findings indicated a strong link between H. pylori and non-cardia gastric cancer (NCGC) in both Europe/North America (OR=5.37, 95%CI:4.39-6.57) and Asia (OR = 2.50, 95%CI:1.89-3.32), and a positive association with cardia gastric cancer (CGC) in Asia (OR = 1.74, 95%CI:1.38-2.19), but an inverse association in European/American populations (OR = 0.64, 95%CI: 0.51 to 0.79). Furthermore, the strength of association was greater in studies that detected H. pylori by immunoblotting versus ELISA, and also in studies testing for H. pylori detection further back in time prior to cancer diagnosis (Ptrend<0.05). Approximately 79% of NCGC in Asia and 87% in Europe/North America, along with 62% of CGC in Asia, could be attributable to H. pylori infection.Conclusions: The meta-analysis supports the significant attributable risk of H. pylori infection for GC and underscores the potential impact of targeting H. pylori in GC prevention programs.

    ...
  • 2.Prediction Models for Gastric Cancer Risk in the General Population: A Systematic Review

    • 关键词:
    • SERUM PEPSINOGEN; TOOL; EXPLANATION; VALIDATION; ANTIBODY

    Risk prediction models for gastric cancer could identify high-risk individuals in the general population. The objective of this study was to systematically review the available evidence about the construction and verification of gastric cancer predictive models. We searched PubMed, Embase, and Cochrane Library databases for articles that developed or validated gastric cancer risk prediction models up to November 2021. Data extracted included study characteristics, predictor selection, missing data, and evaluation metrics. Risk of bias (ROB) was assessed using the Prediction model Risk Of Bias Assessment Tool (PROBAST). We identified a total of 12 original risk prediction models that fulfilled the criteria for analysis. The area under the receiver operating characteristic curve (AUC) ranged from 0.73 to 0.93 in derivation sets (n = 6), 0.68 to 0.90 in internal validation sets (n = 5), 0.71 to 0.92 in external validation sets (n = 7). The higher-performing models usually include age, salt preference, Helicobacter pylori, smoking, body mass index, family history, pepsinogen, and sex. According to PROBAST, at least one domain with a high ROB was present in all studies mainly due to methodologic limitations in the analysis domain. In conclusion, although some risk prediction models including similar predictors have displayed sufficient discriminative abilities, many have a high ROB due to methodologic limitations and are not externally validated efficiently. Future prediction models should adherence to well-established standards and guidelines to benefit gastric cancer screening.Prevention Relevance: Through systematical reviewing available evidence about the construction and verification of gastric cancer predictive models, we found that most models have a high ROB due to methodologic limitations and are not externally validated efficiently. Future prediction models are supposed to adherence to well-established standards and guidelines to benefit gastric cancer screening.

    ...
  • 3.A pan-cancer analysis of thioredoxin-interacting protein as an immunological and prognostic biomarker.

    • 关键词:
    • ;

    BACKGROUND: The critical role of thioredoxin-interacting protein (TXNIP) in cellular sulfhydryl redox homeostasis and inflammasome activation is already widely known, however, no pan-cancer analysis is currently available.; METHODS: We thus first explored the potential roles of TXNIP across thirty-three tumors mainly based on The Cancer Genome Atlas and Gene Expression Omnibus datasets.; RESULTS: TXNIP is lowly expressed in most cancers, and distinct associations exist between TXNIP expression and the prognosis of tumor patients. TXNIP expression was associated with tumor mutational burden, microsatellite instability, mismatch repair genes, tumor infiltrating immune cell abundance as well as cancer-associated fibroblasts. Moreover, ubiquitin mediated proteolysis, protein post-translational modification and other related pathways were involved in the functional mechanisms of TXNIP.; CONCLUSIONS: Our first pan-cancer study comprehensively revealed the carcinostatic role of TXNIP across different tumors. And this molecule may be considered as a potential immunological and prognostic biomarker. © 2022. The Author(s).

    ...
  • 4.Prediction Models for Gastric Cancer Risk in the General Population: A Systematic Review

    • 关键词:
    • SERUM PEPSINOGEN; TOOL; EXPLANATION; VALIDATION; ANTIBODY

    Risk prediction models for gastric cancer could identify high-risk individuals in the general population. The objective of this study was to systematically review the available evidence about the construction and verification of gastric cancer predictive models. We searched PubMed, Embase, and Cochrane Library databases for articles that developed or validated gastric cancer risk prediction models up to November 2021. Data extracted included study characteristics, predictor selection, missing data, and evaluation metrics. Risk of bias (ROB) was assessed using the Prediction model Risk Of Bias Assessment Tool (PROBAST). We identified a total of 12 original risk prediction models that fulfilled the criteria for analysis. The area under the receiver operating characteristic curve (AUC) ranged from 0.73 to 0.93 in derivation sets (n = 6), 0.68 to 0.90 in internal validation sets (n = 5), 0.71 to 0.92 in external validation sets (n = 7). The higher-performing models usually include age, salt preference, Helicobacter pylori, smoking, body mass index, family history, pepsinogen, and sex. According to PROBAST, at least one domain with a high ROB was present in all studies mainly due to methodologic limitations in the analysis domain. In conclusion, although some risk prediction models including similar predictors have displayed sufficient discriminative abilities, many have a high ROB due to methodologic limitations and are not externally validated efficiently. Future prediction models should adherence to well-established standards and guidelines to benefit gastric cancer screening.Prevention Relevance: Through systematical reviewing available evidence about the construction and verification of gastric cancer predictive models, we found that most models have a high ROB due to methodologic limitations and are not externally validated efficiently. Future prediction models are supposed to adherence to well-established standards and guidelines to benefit gastric cancer screening.

    ...
  • 5.Association between oral microflora and gastrointestinal tumors

    • 关键词:
    • oral microorganisms; upper gastrointestinal cancer; chronicinflammation; carcinogens; host metabolism;SQUAMOUS-CELL CARCINOMA; RIBOSOMAL-RNA GENE; NF-KAPPA-B; ESOPHAGEALCANCER; ACETALDEHYDE PRODUCTION; MICROBIOME COMPOSITION;BARRETTS-ESOPHAGUS; MOLECULAR ANALYSIS; GUT MICROBIOTA; RISK

    The oral cavity contains the highest density and the most species of microorganisms compared with other parts of the body. Recent studies have determined that the species and abundance of oral microflora are closely associated with the development of upper gastrointestinal tumors, including oral, esophageal and gastric cancer. Additionally, differential abundant microbiota in patients with cancer and abnormal microorganisms inside the tumor tissue have been identified as critical markers of tumorigenesis. There is evidence to suggest that certain genera, including Firmicutes, along with various species, such as Porphyromonas, can increase the risk of oral cancer. Furthermore, Porphyromonas gingivalis is a risk factor for esophageal carcinoma, while Helicobacter pylori infections are a main cause of gastric cancer. Currently, as far as carcinogenic mechanisms of oral microorganisms are concerned, it has been hypothesized that the production of carcinogenic substances, chronic inflammation and altered cell metabolisms may be mechanisms by which oral microorganisms influence the development of upper gastrointestinal cancer. Certain phrases, including 'oral microbes', 'oral microorganism', 'oral microbiology', 'oral microflora', 'oral cancer', 'oral carcinoma', 'carcinoma of mouth', 'esophagus cancer', 'esophageal cancer', 'esophageal carcinoma', 'carcinoma of esophagus', 'gastric cancer', 'gastric carcinoma', 'stomach cancer', 'cancer of the stomach', 'carcinogenic mechanism' and 'carcinogenesis', were searched as key words in PubMed and Web of Science for articles published between 1975 to 2020. A total of 1,512 studies were obtained. After further searching the abstracts for key words, such as oral microorganisms, oral cancer, esophagus cancer, gastric cancer and carcinogenic mechanisms, 137 studies were selected. The current review systematically and comprehensively summarized the association between the oral microbiota and oral, esophageal and gastric cancer. Additionally, the current review described the carcinogenic mechanisms of oral microbes and attempted to identify common molecular mechanisms among different types of tumor. The association between upper gastrointestinal cancer therapy and oral microflora was also assessed. The present review may be used as a reference for future diagnosis and therapeutics for upper gastrointestinal tumors.

    ...
  • 6.[Analysis of the effects of esophageal cancer screening in Henan rural areas with cancer screening program, 2014-2018].

    • 关键词:
    • ;

    Objective: To analyze the effects of esophageal cancer screening in Henan rural areas with cancer screening program from 2014 to 2018. Methods: From July 2014 to June 2019, according to the National Early Diagnosis and Treatment of Upper Gastrointestinal Cancer in Rural Areas Project, cluster sampling method was adopted in 16 counties/county-level cities in rural areas with high incidence of esophageal cancer in Henan province. Endoscopic iodine staining and indicative biopsy were used to screen esophageal cancer. The patients with mild and moderate dysplasia confirmed in screening were followed up. The distribution of esophageal diseases in the screening population was calculated, and Chi-square test was used to compare the differences of detection rate and early diagnosis rate between the primary screening population and the follow-up population. Results: The age of 116 630 primary screening population was (54.29±7.70) years old, and the proportion of males was 41.2% (48 108). In the primary screening population, patients with normal esophagus, mild to moderate dysplasia, severe dysplasia and above accounted for 92.91% (108 363), 6.03% (7 035) and 1.06% (1 232), respectively. The detection rate of esophageal cancer was 1.06% (1 232/116 630), and the rate of early diagnosis was 85.80% (1 057). Among the follow-up population of 6 154 people, those with normal esophagus, mild to moderate dysplasia, severe dysplasia and above diseases accounted for 63.45% (3 905), 33.13% (1 519) and 3.41% (210), respectively. The detection rate of esophageal cancer was 3.41% (210/6 154), and the rate of early diagnosis was 91.90% (1 939). Compared with the primary screening population, the risk of esophageal cancer was higher in the overall follow-up population, people either with mild or with moderate dysplasia diagnosed in primary screening, with OR values (95%CI) of 3.23 (2.78, 3.75), 1.85 (1.49, 2.29) and 8.13 (6.69, 9.88), respectively. Conclusion: From 2014 to 2018, in the early diagnosis and early treatment of upper digestive tract cancer project in rural areas of Henan Province, the detection rate of the follow-up population is significantly higher than that of the primary screening population. Improving follow-up rate and paying more attention to the screening of people who need follow-up could further improve the screening effect.

    ...
  • 7.Association between oral microflora and gastrointestinal tumors

    • 关键词:
    • oral microorganisms; upper gastrointestinal cancer; chronicinflammation; carcinogens; host metabolism;SQUAMOUS-CELL CARCINOMA; RIBOSOMAL-RNA GENE; NF-KAPPA-B; ESOPHAGEALCANCER; ACETALDEHYDE PRODUCTION; MICROBIOME COMPOSITION;BARRETTS-ESOPHAGUS; MOLECULAR ANALYSIS; GUT MICROBIOTA; RISK

    The oral cavity contains the highest density and the most species of microorganisms compared with other parts of the body. Recent studies have determined that the species and abundance of oral microflora are closely associated with the development of upper gastrointestinal tumors, including oral, esophageal and gastric cancer. Additionally, differential abundant microbiota in patients with cancer and abnormal microorganisms inside the tumor tissue have been identified as critical markers of tumorigenesis. There is evidence to suggest that certain genera, including Firmicutes, along with various species, such as Porphyromonas, can increase the risk of oral cancer. Furthermore, Porphyromonas gingivalis is a risk factor for esophageal carcinoma, while Helicobacter pylori infections are a main cause of gastric cancer. Currently, as far as carcinogenic mechanisms of oral microorganisms are concerned, it has been hypothesized that the production of carcinogenic substances, chronic inflammation and altered cell metabolisms may be mechanisms by which oral microorganisms influence the development of upper gastrointestinal cancer. Certain phrases, including 'oral microbes', 'oral microorganism', 'oral microbiology', 'oral microflora', 'oral cancer', 'oral carcinoma', 'carcinoma of mouth', 'esophagus cancer', 'esophageal cancer', 'esophageal carcinoma', 'carcinoma of esophagus', 'gastric cancer', 'gastric carcinoma', 'stomach cancer', 'cancer of the stomach', 'carcinogenic mechanism' and 'carcinogenesis', were searched as key words in PubMed and Web of Science for articles published between 1975 to 2020. A total of 1,512 studies were obtained. After further searching the abstracts for key words, such as oral microorganisms, oral cancer, esophagus cancer, gastric cancer and carcinogenic mechanisms, 137 studies were selected. The current review systematically and comprehensively summarized the association between the oral microbiota and oral, esophageal and gastric cancer. Additionally, the current review described the carcinogenic mechanisms of oral microbes and attempted to identify common molecular mechanisms among different types of tumor. The association between upper gastrointestinal cancer therapy and oral microflora was also assessed. The present review may be used as a reference for future diagnosis and therapeutics for upper gastrointestinal tumors.

    ...
  • 8.Risk Prediction Model for Esophageal Cancer Among General Population: A Systematic Review

    Objective: The risk prediction model is an effective tool for risk stratification and is expected to play an important role in the early detection and prevention of esophageal cancer. This study sought to summarize the available evidence of esophageal cancer risk predictions models and provide references for their development, validation, and application.Methods: We searched PubMed, EMBASE, and Cochrane Library databases for original articles published in English up to October 22, 2021. Studies that developed or validated a risk prediction model of esophageal cancer and its precancerous lesions were included. Two reviewers independently extracted study characteristics including predictors, model performance and methodology, and assessed risk of bias and applicability with PROBAST (Prediction model Risk Of Bias Assessment Tool).Results: A total of 20 studies including 30 original models were identified. The median area under the receiver operating characteristic curve of risk prediction models was 0.78, ranging from 0.68 to 0.94. Age, smoking, body mass index, sex, upper gastrointestinal symptoms, and family history were the most commonly included predictors. None of the models were assessed as low risk of bias based on PROBST. The major methodological deficiencies were inappropriate date sources, inconsistent definition of predictors and outcomes, and the insufficient number of participants with the outcome.Conclusions: This study systematically reviewed available evidence on risk prediction models for esophageal cancer in general populations. The findings indicate a high risk of bias due to several methodological pitfalls in model development and validation, which limit their application in practice.

    ...
  • 9.Precision screening for esophageal squamous cell carcinoma in China

    • 关键词:
    • Esophageal cancer; organized screening; opportunistic screening;cost-effectiveness; risk stratification;HIGH-RISK; CANCER-RISK; FOLLOW-UP; POPULATION; LINXIAN; LESIONS;MORTALITY; PROSTATE; REGIONS; TRIAL

    Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in China, and this neoplasm is associated with high morbidity and mortality as well as clear geographical heterogeneity. Since primary prevention for ESCC lacks a clear intervention target, secondary prevention, also known as screening and early diagnosis and early treatment, has become the mainstay of ESCC prevention and control in China. ESCC screening in China has been subject to decades of evaluation and practice. However, the ESCC screening strategy currently adopted in China has encountered a developmental bottleneck. In this review, we have summarized studies and significant findings for ESCC screening and proposed advancement of screening strategies as follows: 1) evidence from randomized controlled trials is needed to support the effectiveness and health economic value of endoscopic screening for ESCC; 2) the current traditional screening and surveillance strategies warrant reform, and a risk-prediction-based precision strategy should be established; and 3) a deeper understanding of the value of opportunistic screening in the prevention and control of ESCC in China is called for. Due to the low absolute prevalence of precancerous lesions, substantial investment of resources and nonnegligible risks of invasive screening techniques, precision and individualization should be the main direction of cancer screening programs for the future. We advocate cooperation on the part of Chinese scientists to solve this major China-specific health problem in the next decades.

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  • 10.Exosome-Derived LncRNAs in Lung Cancer

    • 关键词:
    • exosome; lncRNA; lung cancer; biomarkers; intercellular communication;LONG NONCODING RNAS; PRE-METASTATIC NICHES; EXTRACELLULAR VESICLES;LYSOSOMAL DEGRADATION; TRANSFERRIN RECEPTOR; PROMOTES; CELLS;BIOGENESIS; RESISTANCE; BIOMARKERS

    As extracellular vesicles, exosomes are released from most cells to perform cell-cell communication. Recent studies have shown that exosomes could be released into tumor microenvironment and blood to promote tumor progression through packaging and transmitting various bioactive molecules, such as cholesterol, proteins, lipids, miRNAs, mRNAs, and long non-coding RNAs (lncRNAs) to distant cells. LncRNAs have emerged as a major class of non-coding transcripts. A lot of LncRNAs have been discovered during the past few years of research on genomics. They have been proven to participate in various biological functions and disease processes through multiple mechanisms. In this review, we analyzed the role of exosome-derived lncRNAs in lung carcinogenesis and metastasis. We also highlight opportunities for the clinical potential of exosomes with specific lncRNAs as biomarkers and therapeutic intervention in lung cancer.

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