Mechanisms and Management of Familial Colon Cancer

家族性结肠癌的机制和治疗

基本信息

批准号：
7277837
负责人：
Harvey J. Murff
金额：
$ 13.03万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7277837
关键词：
Adenomatous Polyposis Coli Affect Age-Years Alcohol consumption Award Cancer Biology Cancer Burden Cancer Control Cancer Patient Case-Control Studies Cessation of life Cigarette Clinical Management Clinical Medicine Collaborations Colon Carcinoma Colonic Adenoma Colorectal Cancer Colorectal Polyp Complex Condition Data Death Rate Development Development Plans Diabetes Mellitus Diagnosis Disease Early Diagnosis Early identification Economic Burden Ensure Environmental Risk Factor Epidemiology Etiology Family Family Cancer History Family history of Folate Foundations Future Genetic Genetic Polymorphism Genetic Variation Genomics Goals Grant Health Services Research Hereditary Nonpolyposis Colorectal Neoplasms Individual Inflammatory Inherited Intervention Intestines K-Series Research Career Programs Knowledge Large Intestine Carcinoma Life Style MADH2 gene MADH4 gene Malignant Neoplasms Mentored Clinical Scientist Development Award (K08)Mentors Mentorship Molecular Biology Molecular Epidemiology National Health Interview Survey Pathogenesis Phase Population Sciences Predisposition Prevention Prevention program Range Rate Recording of previous events Relative (related person)Research Research Personnel Research Project Grants Research Proposals Risk Risk Factors Risk Reduction Science Scientist Screening for cancer Screening procedure Services Signal Pathway Specific qualifier value Survival Rate Syndrome Tennessee Transforming Growth Factor beta Transforming Growth Factor beta Receptors Translating United States Work adenoma base burden of illness cancer epidemiology cancer genetics career clinical application colorectal cancer screening cost effectiveness design experience genetic epidemiology human TGFB1 protein improved models and simulation mortality novel red meat consumption skills

项目摘要

DESCRIPTION (provided by applicant): Advances in genomics offer the potential for novel clinical applications designed to identify individuals at greater susceptibility to cancer and develop personalized risk-reduction strategies. As such, the family history assessment is becoming increasingly important for cancer control and prevention. While significant advances have been made in our understanding of the etiology and clinical management in inherited colorectal cancer syndromes, such as familial adenomatous polyposis or hereditary non-polyposis colorectal cancer, most individuals with a family history of colorectal cancer do not have one of these well-described, Mendelian conditions. Our understanding of the mechanisms underlying the familial aggregation of colorectal cancers and the most effective screening strategies for individuals at increased risk for colorectal cancer remains limited. The long-term goals of Dr. Murff is to better delineate the complex genetic and environmental factors associated with familial colorectal cancer and translate these findings into improved management of high-risk individuals. The research aims of this proposal include: 1) To determine the effect of a family history of colon cancer on the initiation of colorectal cancer screening interventions; 2) To determine if an interaction exists between having affected relatives with colorectal cancer and patient lifestyle factors on adenoma risk; 3) To evaluate the relationship of functional genetic polymorphisms within the transforming growth factor beta signaling pathway to colonic adenoma risk and family colon cancer history; 4) To determine the cost-effectiveness of colorectal cancer screening in individuals at increased risk based on their family history. The early phases of this career development award will build on the candidate's prior work and determine current practices for cancer screening in high-risk individuals. Through the candidate's didactic coursework and mentorship plan, Dr. Murff will develop additional skills in genetics, cancer biology, and molecular epidemiology. The latter phases of the award will build on this new knowledge to investigate the genetic underpinnings of familial colon cancer. The experience gained from this career development award will ensure Dr. Murff's transition into an independent researcher in cancer epidemiology.

描述（由申请人提供）：基因组学的进步为新型临床应用提供了潜力，旨在识别对癌症敏感性更大并制定个性化风险降低策略的个人。因此，对癌症控制和预防的家族史评估变得越来越重要。尽管我们对遗传性结直肠癌综合征的病因和临床管理的理解已经取得了重大进展，例如家族性腺瘤性息肉病或遗传性非poly型大肠癌，但大多数患有结直肠癌家族史的人都没有这些描述良好的Mendelian疾病。我们对结直肠癌家族聚集的基础机制以及对大肠癌风险增加的个体最有效的筛查策略的理解仍然有限。 Murff博士的长期目标是更好地描述与家族性结肠癌相关的复杂遗传和环境因素，并将这些发现转化为改善高风险个体的管理。该提案的研究目的包括：1）确定结肠癌家族史对结肠癌筛查干预措施的效果； 2）确定在患有结直肠癌的亲属与患者生活方式因素因腺瘤风险中是否存在相互作用； 3）评估在转化生长因子beta信号传导途径到结肠腺瘤风险和家庭结肠癌史的功能遗传多态性的关系； 4）确定基于家族史，在风险增加的个体中大肠癌筛查的成本效益。该职业发展奖的早期阶段将基于候选人的先前工作，并确定高风险个体癌症筛查的当前做法。通过候选人的教学课程和指导计划，Murff博士将在遗传学，癌症生物学和分子流行病学方面发展其他技能。该奖项的后一个阶段将基于这种新知识，以研究家族性结肠癌的遗传基础。从这个职业发展奖中获得的经验将确保Murff博士转变为癌症流行病学独立研究人员。