Susceptibility Markers for a Breast-Colon Cancer Phenotype

描述（由申请人提供）：该职业发展奖的目的是为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。该建议建立在她之前作为结直肠癌研究的癌症预防科学家的培训基础上，并概述了在乳腺癌研究，遗传学和遗传分析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Pande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，成为一名独立研究者的总体目标。她将通过课程作业、工作坊、研讨会和指导研究的结合来完成该提案的目标。课程将着重于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。一个高素质的导师和合作者团队将监督她的培训并指导她的研究，以确保她实现自己的目标。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项的目标。该提案的研究部分包括检查乳腺癌和结肠癌表型的易感性标记，其特征是乳腺癌和结肠癌在个人和家庭中共同发生。总的来说，乳腺癌和结直肠癌是一个重要的癌症负担，通常在没有已知遗传易感性或综合征的家庭中同时发生。确定这些高风险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，具体目的是：1)通过检测全基因组关联研究（genome-wide association study， GWAS）数据，确定与乳腺癌表型相关的遗传易感标志物；2)在潜在遗传风险背景下，确定流行病学危险因素与乳腺癌结肠表型的关系；

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.