Modeling Colon Cancer, Intervention and Prevention

结肠癌建模、干预和预防

• 批准号: 7360317
• 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
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7360317
• 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

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）：致癌作用的数学模型旨在捕捉多阶段过程的重要特征，从正常细胞，通过扩大中间细胞群，到恶性肿瘤的出现，提供了更详细地研究影响致癌作用中关键生物过程的特定干预措施的效果的机会。因此，该提案的主要重点是开发工具和方法，用于定量评估可能的预防和干预策略，并将其应用于结直肠癌。这些工具和方法将基于致癌作用的随机模型，这些模型反映了过去十年来对结肠癌发病机制的认识，以及这些模型的扩展，这些模型允许纳入与基因组不稳定性相关的其他（推定）途径。为了有信心地实现这一目标，重要的是用于此目的的模型提供了令人满意的描述在一般人群中的结肠癌的发病率。一个挑战，迄今尚未满足的是，这些模型也与腺瘤性息肉的患病率和大小分布的观察结果一致，病理学特征良好的前体病变的结直肠肿瘤。这些息肉也是特定癌症筛查和干预策略的对象。这激发了统计和计算工具的数学发展，以分析相关数据集：（1）关于结直肠癌（CRC）发病率的SEER登记数据，（2）大型前瞻性女性队列中的CRC发病率（上海研究），（3）明尼苏达州癌症预防研究单位（CPRU）息肉数据，（4）来自Fred哈钦森癌症研究中心进行的结直肠癌病例对照研究和乙状结肠镜检查的数据。从这些分析和开发的计算工具中得出的模型将有助于预测与特定筛查、预防和干预策略相关的益处。