Genetic and Epidemiological Approaches to Breast Density and Breast Cancer Risk

描述（由申请人提供）：申请人Elad Ziv博士是加州大学旧金山分校的医学副教授，领导一个以患者为导向的研究项目，研究常见癌症和血液学特征的遗传易感性。Ziv博士项目的一个主要重点是研究乳腺癌易感性的遗传因素。作为这项计划的一部分，博士。 Ziv将寻找乳腺密度和乳腺癌风险之间联系的遗传因素。乳房X线摄影乳腺密度已知是乳腺癌的一个强有力的危险因素，也是一个高度遗传的性状。Ziv博士将分析他的团队正在进行的一项大型全基因组关联研究（GWAS），将年龄和BMI调整的乳腺密度最高的五分之一的500名女性与最低的五分之一的500名女性进行比较。他将对年龄和BMI调整密度的另外500名女性和500名女性的复制数据集中的前1500个变异进行复制分析。此外，他的研究小组将寻找与乳腺密度和乳腺癌风险相关的遗传变异。他们将对乳腺密度和乳腺癌GWAS数据集进行综合分析，使用他的团队生成的乳腺癌易感性GWAS数据集和公开可用的乳腺癌GWAS数据集。Ziv博士及其同事还将使用下一代测序技术来寻找可能解释这些特征之间重叠的罕见变异。特别是，具有乳腺癌家族史且年龄和BMI调整的乳腺密度也处于前五分位的女性将被选择用于全外显子组测序。作为这项提议的一部分，Ziv博士将扩大他指导初级研究人员的能力，并发展额外的技能，以最大限度地发挥他作为导师的潜力。Ziv博士指导了超过15名初级教师，研究员，居民和学生。他隶属于3个T32项目的指导研究员。Ziv博士将在博士后水平上接受更多的学员，并继续指导目前与他一起工作的初级教师。他还将继续接受额外的培训，以提高他的指导和科学技能。

DESCRIPTION (provided by applicant): The applicant, Dr. Elad Ziv, is an associate professor of medicine at UCSF and leads a patient oriented research program that investigates genetic susceptibility to common cancers and hematological traits. A major focus of Dr. Ziv's program is the study of genetic factors underlying breast cancer susceptibility. As part of this proposal, Dr. Ziv will search for genetic factors underlying the association between mammographic breast density and breast cancer risk. Mammographic breast density is known to be a strong risk factor for breast cancer and is also a highly heritable trait. Dr. Ziv will analyze a large genome wide association study (GWAS) that his group is generating, comparing 500 women from the top quintile of age and BMI-adjusted breast density to 500 women from the bottom quintile. He will perform a replication analysis of the top 1500 variants in a replication dataset of another 500 women from the top and 500 women from the bottom quintile of age and BMI adjusted density. In addition, his group will search for genetic variants that are associated with both breast densit and breast cancer risk. They will perform a combined analysis of breast density and breast cancer GWAS datasets, using GWAS datasets of breast cancer susceptibility that his group has generated and a publicly available breast cancer GWAS datasets. Dr. Ziv and colleagues will also use next generation sequencing to search for rare variants that may explain the overlap between these traits. In particular, women with a strong family history of breast cancer who are also in the top quintile of age and BMI-adjusted breast density will be selected for whole exome sequencing. As part of this proposal, Dr. Ziv will expand his capacity to mentor junior investigators and develop additional skills to maximize his potential as a mentor. Dr. Ziv has mentored over 15 junior faculty members, fellows, residents and students. He is affiliated with 3 T32 programs for mentoring fellows. As part of this proposal, Dr. Ziv will take on additional mentees at the post-doctoral level and continue to mentor the junior faculty, fellows currently working with him. He will also pursue additional training that will enhance his mentoring and scientific skills.