Susceptibility Markers for a Breast-Colon Cancer Phenotype

描述(由申请人提供)：该职业发展奖的目标是为Mala Pande博士提供必要的知识和经验，使其成为癌症预防研究领域的独立遗传流行病学家，专门研究遗传性和家族性癌症。这项建议建立在她之前在结直肠癌研究方面作为癌症预防科学家的培训基础上，并概述了在乳腺癌研究、遗传学和用于基因分析的新兴分析方法方面的进一步培训。拟议的研究和培训计划将使潘德博士能够发展内容领域知识、研究方法技能和学术生存技能，最终目标是成为一名独立的研究人员。她将通过课程作业、研讨会、研讨会和有指导的研究相结合的方式来实现这项提案的目标。课程的重点将是加强她在癌症生物学、统计遗传学和全基因组关联分析方面的培训。一个由高素质的导师和合作者组成的团队将监督她的培训并指导她的研究，以确保她达到目标。该机构(MD安德森癌症中心)致力于为她提供必要的保护时间、空间和资源，以实现这一职业发展奖的目标。这项建议的研究内容包括检查乳腺癌-结肠癌表型的易感标记物，这种表型的特征是乳腺癌和结肠癌在个人和家庭中共同发生。乳腺癌和结直肠癌总体上占癌症负担的很大一部分，通常被认为是同时发生在没有已知遗传倾向或症状的家庭中。识别这些高危家庭可以提供显著的癌症预防益处。为了实现本研究的目标，本研究的具体目标是：1)通过检查全基因组关联研究数据，确定与乳腺-结肠癌表型相关的遗传易感标记；2)在潜在的遗传风险描述的背景下，确定流行病学危险因素与乳腺-结肠癌表型的关联； 3)确定含有与疾病表型相关的基因座的区域中可能存在的功能变异。这些具体目标将使用乳腺癌和结肠癌家庭登记(CFR)的二次数据来实现，这两个CFR都已获得批准。母体乳腺癌和结直肠癌GWAS的主要研究人员是她研究的顾问，并将为她的项目分享他们的专业知识。这项拟议的研究将提供关于这种尚未被很好理解的相当常见的表型的风险的遗传和非遗传预测因素的重要知识。此外，这些研究将为申请者提供初步数据，以开发进一步的假设，以了解和解决乳腺癌-结肠癌和多发性癌症易感性个人和家庭的长期癌症风险。这项研究的癌症预防目标是确定 癌症高危人群，对他们来说，筛查和早期发现最有利于减轻癌症负担。

DESCRIPTION (provided by applicant): The objective of this career development award is to provide Dr. Mala Pande with the knowledge and experience necessary to become an independent genetic epidemiologist in the field of cancer prevention research, specializing in hereditary and familial cancers. This proposal builds upon her previous training as a cancer prevention scientist in colorectal cancer research, and outlines further training in breast cancer research, genetics and emerging analytic approaches for genetic analyses. The proposed research and training plan will allow Dr. Pande to develop content area knowledge, research methods skills and academic survival skills with the overarching goal of becoming an independent investigator. She will accomplish the goals of this proposal through a combination of coursework, workshops, seminars and mentored research. The coursework will be focused on enhancing her training in cancer biology, statistical genetics and advances in genome-wide association analyses. A highly qualified team of mentors and collaborators will supervise her training and guide her research to ensure that she meets her goals. The institution (MD Anderson Cancer Center) is committed to providing her with the protected time, space and resources necessary to achieve the goals of this career development award. The research component of this proposal involves examining susceptibility markers for a breast-colon cancer phenotype, which is characterized by co-occurrence of breast and colon cancer among individuals and families. Breast and colorectal cancer account for a significant cancer burden overall and are often seen to occur together in families with no known genetic predisposition or syndromes. Identifying these high risk families can provide a significant cancer prevention benefit. To achieve the goals of this research, the specific aims are: 1) To determine genetic susceptibility markers associated with the breast-colon cancer phenotype by examining genome-wide association study (GWAS) data; 2) To determine the association of epidemiologic risk factors with the breast-colon phenotype in the context of the underlying genetic risk profile; and 3) To ascertain possible functional variants in the regions containing loci associated with the disease phenotype. These specific aims will be accomplished using secondary data from the Breast and Colon Cancer Family Registries (CFRs) for which approvals are in place from both CFRs. The principal investigators of the parent breast cancer GWAS and colorectal cancer GWAS are consultants for her study and will share their expertise for her project. The proposed research will provide important knowledge regarding the genetic and non-genetic predictors of risk for this fairly common phenotype that is not well understood. In addition, these studies will provide the applicant with preliminary data to develop further hypothesis for understanding and addressing cancer risk in the breast-colon and multiple cancer predisposed individuals and families over the longer term. The cancer prevention goal of this research is the identification of individuals at high risk for cancer development for whom screening and early detection would be most beneficial in reducing the burden of cancer.