Mechanisms and Management of Familial Colon Cancer

描述(由申请人提供)：基因组学的进步为新的临床应用提供了潜力，旨在识别更容易患癌症的个人，并开发个性化的风险降低策略。因此，家族史评估对于癌症控制和预防正变得越来越重要。虽然我们对遗传性结直肠癌综合征(如家族性腺瘤性息肉病或遗传性非息肉病性结直肠癌)的病因和临床处理方面的了解已经取得了重大进展，但大多数有结直肠癌家族史的人并没有这些描述良好的孟德尔条件。我们对结直肠癌家族聚集的机制以及对结直肠癌高危个体最有效的筛查策略的了解仍然有限。默夫博士的长期目标是更好地描述与家族性结直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对高危个体的管理。这项建议的研究目的包括：1)确定结肠癌家族史对启动结直肠癌筛查干预措施的影响；2)确定受影响的结直肠癌亲属和患者生活方式因素对腺瘤风险是否存在交互作用；3)评估转化生长因子β信号通路功能基因多态性与结肠腺瘤风险和结肠癌家族史的关系；4)根据家族史确定在高危人群中进行结直肠癌筛查的成本效益。这一职业发展奖的早期阶段将建立在候选人以前的工作基础上，并确定目前在高危个人中进行癌症筛查的做法。通过候选人的授课课程和导师计划，默夫博士将在遗传学、癌症生物学和分子流行病学方面发展更多的技能。该奖项的后几个阶段将建立在这一新知识的基础上，以调查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默夫博士过渡到癌症流行病学的独立研究人员。

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.