Susceptibility Markers for a Breast-Colon Cancer Phenotype

乳腺癌结肠癌表型的易感性标志物

• 批准号: 8706826
• 负责人: Mala Pande
• 金额: $ 12.05万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-05 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8706826
• 关键词: Accounting; Address; Age; Age of Onset; Alcohol consumption; Area; BRCA1 gene; BRCA2 gene; Bioinformatics; Body mass index; Breast; CHEK2 gene; Cancer Biology; Cancer Burden; Cancer Center; Cancer Family; Case-Control Studies; Collaborations; Colon; Colon Carcinoma; Colorectal Cancer; Commit; Data; Development; Development Plans; Early Diagnosis; Educational workshop; Ensure; Epidemiologist; Epidemiology; Family; Family member; Family-Based Registry; Frequencies; Gender; Genes; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genetic Risk; Genome; Goals; Haplotypes; Hereditary Malignant Neoplasm; Hereditary Nonpolyposis Colorectal Neoplasms; Heterogeneity; High-Risk Cancer; Hormones; Individual; Inherited; Institution; K-Series Research Career Programs; Knowledge; Linkage Disequilibrium; Malignant Neoplasms; Mentors; Methods; Mutation; Parents; Pathway interactions; Peutz-Jeghers Syndrome; Phenotype; Physical activity; Predisposition; Prevention; Prevention Research; Principal Investigator; Qualifying; Recruitment Activity; Registries; Research; Research Design; Research Methodology; Research Personnel; Research Project Grants; Research Training; Resources; Risk; Risk Factors; Risk Marker; Sampling; Scientist; Smoking; Susceptibility Gene; Syndrome; Time; Training; Variant; anticancer research; base; cancer genome; cancer prevention; cancer risk; career development; clinical practice; colon cancer family registry; disease phenotype; experience; gene environment interaction; genetic analysis; genetic risk factor; genome wide association study; genome-wide analysis; high risk; lifestyle factors; malignant breast neoplasm; meetings; non-genetic; novel; population based; screening; skills; skills training; tool

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.

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。这项建议建立在她以前作为结直肠癌研究的癌症预防科学家的培训基础上，并概述了乳腺癌研究，遗传学和遗传分析的新兴分析方法的进一步培训。拟议的研究和培训计划将使Pande博士能够发展内容领域的知识，研究方法技能和学术生存技能，其总体目标是成为一名独立的研究者。她将通过课程，讲习班，研讨会和指导研究的结合来实现本提案的目标。该课程将侧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的进展方面的培训。一个高素质的导师和合作者团队将监督她的培训和指导她的研究，以确保她达到她的目标。该机构（MD安德森癌症中心）致力于为她提供实现该职业发展奖目标所需的受保护的时间、空间和资源。该提案的研究部分涉及检查乳腺癌-结肠癌表型的易感性标志物，其特征在于个体和家庭中乳腺癌和结肠癌的共同发生。乳腺癌和结直肠癌占总体癌症负担的重要部分，并且通常在没有已知遗传易感性或综合征的家庭中一起发生。识别这些高风险家庭可以提供显着的癌症预防益处。为了实现本研究的目标，具体的目的是：1）通过检查全基因组关联研究（GWAS）数据，确定与乳腺-结肠癌表型相关的遗传易感性标记物; 2）在潜在遗传风险特征的背景下，确定流行病学风险因素与乳腺-结肠癌表型的关联; 和3）确定含有与疾病表型相关的基因座的区域中可能的功能变体。这些具体目标将使用来自乳腺癌和结肠癌家族登记处（CFR）的二级数据来实现，这两个CFR均已批准。母公司乳腺癌GWAS和结直肠癌GWAS的主要研究者是她研究的顾问，并将为她的项目分享他们的专业知识。拟议的研究将提供关于这种尚不清楚的相当常见的表型的遗传和非遗传风险预测因素的重要知识。此外，这些研究还将为申请人提供初步数据，以制定进一步的假设，用于了解和解决乳腺-结肠癌和多种癌症易感个体和家庭的长期癌症风险。这项研究的癌症预防目标是识别 癌症发展高风险的个人，对他们来说，筛查和早期发现对减少癌症负担最为有益。