Modeling Colon Cancer, Intervention and Prevention

结肠癌建模、干预和预防

基本信息

批准号：
7183594
负责人：
Georg E. Luebeck
金额：
$ 25.92万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7183594
关键词：
Aberrant crypt foci Accounting Adenomatous Polyps Affect Age Anti-Inflammatory Agents Anti-inflammatory Appearance Area Ascending colon Biological Biological Process Boxing Breast Calendar Caliber Cancer Intervention Cancer Model Carcinoma Carcinoma in Situ Case-Control Studies Cecum Cells Censuses Cessation of life Cities Clinic Code Cohort Studies Colon Colon Carcinoma Colonoscopy Colorectal Colorectal Adenocarcinoma Colorectal Cancer Colorectal Neoplasms Communities Control Groups Data Data Set Data Sources Databases Descending colon Development Diagnosis Diagnostic Disease Distal Eligibility Determination Employee Enrollment Environmental Carcinogens Event Excision Facility Construction Funding Category Failure Family history of Family-Based Registry Female Fred Hutchinson Cancer Research Center Gastroenterology Gender General Population Genetic Genomic Instability Genomics Genus Cola Goals Hemorrhage Histologic Hyperplasia Hyperplastic Polyp Incidence Individual Individual Cancer History Inflammatory Bowel Diseases Intervention Interview Invasive Knowledge Lead Lesion Location Malignant Neoplasms Medical Records Medical Surveillance Methods Minnesota Modeling Mutation Natural History Nature Neoplasms Normal Cell Numbers Odds Ratio Participant Pathogenesis Pathologist Pathology Pathway interactions Patients Persons Pharmaceutical Preparations Polypectomy Polyps Population Predisposition Prevalence Prevention Prevention Research Prevention intervention Prevention strategy Principal Investigator Probability Process Prophylactic treatment Public Health Purpose Quantitative Evaluations Questionnaires Race Range Recording of previous events Recruitment Activity Rectal Adenoma Rectum Registries Reproductive History Research Ethics Committees Risk Factors Role Schedule Screening for cancer Screening procedure Shapes Sigmoid colon Sigmoidoscopy Site Skin Carcinoma Stem cells Study Subject Symptoms Syndrome Testing Textile Industry Time Transverse colon Twin Multiple Birth Universities Woman adenoma age group base blind cancer prevention cancer statistics carcinogenesis case control cohort colorectal cancer screening computerized tools design desire follow-up improved insight male mathematical model member metropolitan models and simulation mortality neoplasm registry programs prospective sex size sound tool tool development trend tumor

项目摘要

DESCRIPTION (provided by applicant): Mathematical models of carcinogenesis that are designed to capture important features of the multistage process, from normal cells, via expanding intermediate cell populations, to the appearance of malignant tumors, offer the opportunity to study in greater detail the effects of specific interventions that affect critical biological processes involved in carcinogenesis. The main focus of this proposal is therefore the development of tools and methods for the quantitative evaluation of possible prevention and intervention strategies and to apply them to colorectal cancer. These tools and methods will be based on stochastic models of carcinogenesis that reflect insights gained into the pathogenesis of colon cancer over the past decade, as well as extensions of these models that allow for the incorporation of additional (putative) pathways associated with genomic instability. To achieve this goal with confidence, it is important that the models used for this purpose give satisfactory descriptions of the incidence of colon cancer in the general population. A challenge, so far unmet, is that these models also be consistent with observations on the prevalence and size distribution of adenomatous polyps, pathologically well-characterized precursor lesions to colorectal tumors. These polyps are also the subject of specific cancer screening and intervention strategies. This motivates the mathematical development of statistical and computational tools to analyze relevant data sets: (1) the SEER registry data on colorectal cancer (CRC) incidence, (2) CRC incidence in a large prospective cohort of women (the Shanghai study), (3) the Minnesota Cancer Prevention Research Unit (CPRU) polyp data, and (4) data from a case-control study of CRC and the role of sigmoidoscopy conducted at the Fred Hutchinson Cancer Research Center. Models derived from these analyses and the computational tools developed will facilitate the prediction of benefits associated with specific screening, prevention and intervention strategies.

描述（由申请人提供）：旨在捕获从正常细胞（通过扩大中间细胞种群到恶性肿瘤的出现）捕获多阶段过程的重要特征的癌变的数学模型，提供了更详细研究影响涉及癌变的关键生物学过程的特定干预措施的效果。因此，该提案的主要重点是开发用于定量评估可能的预防和干预策略的工具和方法，并将其应用于结直肠癌。这些工具和方法将基于癌变的随机模型，这些模型反映了过去十年中结肠癌发病机理的见解，以及这些模型的扩展，这些模型允许融合与基因组不稳定性相关的其他（推定）途径。为了信心实现这一目标，重要的是，用于此目的的模型对一般人群中结肠癌的发生率的描述令人满意。到目前为止，尚未满足的挑战是，这些模型也与观察到腺瘤息肉的患病率和尺寸分布，病理学良好的前体病变对结直肠肿瘤的观察。这些息肉也是特定的癌症筛查和干预策略的主题。这促使统计和计算工具的数学开发以分析相关数据集：（1）SEER注册表关于结直肠癌（CRC）发病率的数据，（2）CRC的发病率（上海研究）（上海研究）（3）（3）（3）明尼苏达州预防研究单位（CPRU）CRC数据和CRC数据（4）CRC的角色（4）CRC的角色（4）在弗雷德·哈钦森癌症研究中心进行的乙状结肠镜检查。从这些分析中得出的模型和开发的计算工具将有助于预测与特定筛查，预防和干预策略相关的收益。