Gene-Nutrient Interactions and Breast Cancer

描述(由申请人提供)：苏珊·斯特克-斯科特，博士，公共卫生硕士，RD，北卡罗来纳大学教堂山分校营养学系研究助理教授。通过这一职业发展奖，她正在寻求分子流行病学和癌症生存方面的培训，以补充她在营养科学和癌症预防方面的强大背景。Steck-Scott博士这项建议的主要导师Marilie Gammon博士是一位著名的乳腺癌流行病学家，在指导年轻研究人员方面拥有丰富的经验。此外，丽莎·凯里博士、罗伯特·米利根博士、迈克尔·谢尔博士和弗雷德·赖特博士都是各自领域的知名研究人员，并已同意成为该项目的共同导师。培训将包括伦理学、分子流行病学、癌症发生学、药理学和生物统计学方面的课程和讲习班，以及学习基因分型技术的实验室经验。这一培训将帮助候选人在癌症研究界开拓独特的利基市场，并在癌症预防和控制中的基因-营养相互作用领域建立独立的研究计划。该奖项的主要焦点是一项研究项目，该项目旨在研究十字花科蔬菜的摄入量与编码代谢酶基因在乳腺癌预防、复发和生存中的多态之间的相互作用。这项拟议的研究利用了一项已经进行的以人群为基础的病例对照研究--长岛乳腺癌研究项目的饮食数据、尿液和血液样本，甘蒙博士是该项目的首席研究员。乳腺癌受试者目前正在接受复发和生存状况的跟踪调查。这项研究的具体目的是：1)在一项基于人群的大型病例对照研究中，检测十字花科蔬菜摄入量、尿中异硫氰酸酯(ITC)排泄与GSTM1、GSTT1和GSTP1基因多态之间的关系，以确定GSTM1、GSTT1和/或GSTP 1基因的非零或激活基因型是否导致ITC尿液排泄增加；以及2)在一项基于人群的大型病例对照研究中，研究十字花科蔬菜消费与GSTM1、GSTT1、GSTP1和CYP 1A1基因多态之间的相互作用与乳腺癌风险的关系；以及3)在一项后续病例研究中，探讨GSTM1、GSTT1和/或GSTP 1基因的非零或激活基因型是否会导致ITC排泄增加。这项研究代表了一个独特的机会，可以检验十字花科蔬菜是否正在改变基因多态在乳腺癌预防、复发和生存中的作用。通过确定哪些人可能在基因上更容易受到十字花科蔬菜摄取的好处的影响，未来和正在进行的干预措施可能会变得更有效，因为目标是那些将获得最大好处的人。

DESCRIPTION (provided by applicant): Susan Steck-Scott, PhD, MPH, RD is a research assistant professor in the Department of Nutrition at the University of North Carolina at Chapel Hill. Through this Career Development Award, she is seeking training in molecular epidemiology and cancer survivorship to complement her strong background in the nutritional sciences and cancer prevention. Dr. Steck-Scott's primary mentor for this proposal, Dr. Marilie Gammon, is a renowned breast cancer epidemiologist with extensive experience in mentoring young investigators. In addition, Drs. Lisa Carey, Robert Millikan, Michael Schell and Fred Wright are well established investigators in their fields and have agreed to be co-mentors on this project. Training will include coursework and workshops in ethics, molecular epidemiology, carcinogenesis, pharmacology, and biostatistics, as well as a laboratory experience to learn the techniques of genotyping. This training will help the candidate to develop a unique niche in the cancer research community and establish an independent research program in the area of gene-nutrient interactions in cancer prevention and control. The primary focus of the award is a research project to examine the interaction between cruciferous vegetable intake and polymorphisms in genes encoding metabolizing enzymes in breast cancer prevention, recurrence and survival. The proposed research capitalizes on dietary data, urine and blood samples available from an already conducted population-based, case-control study, the Long Island Breast Cancer Study Project of which Dr. Gammon is the Principal Investigator. Breast cancer subjects are currently being followed up for recurrence and survival status. The specific aims of the research are 1) to examine the associations between cruciferous vegetable intake, urinary isothiocyanate (ITC) excretion, and polymorphisms in GSTM1, GSTT1 and GSTP1 in control subjects to determine whether having the non-null or active genotype for GSTM1, GSTT1 and/or GSTP 1 results in increased urinary excretion of ITC; and 2) to examine the interaction between cruciferous vegetable consumption and polymorphisms in GSTM 1, GSTT 1, GSTP 1 and CYP 1A 1 in relation to breast cancer risk in a large population-based case-control study; and 3) to examine the interaction in relation to breast cancer recurrence and survival in a follow-up study of the cases. This study represents a unique opportunity to examine whether cruciferous vegetables are modifying the effect of genetic polymorphisms in breast cancer prevention, recurrence and survival. By identifying those individuals who may be genetically more susceptible to the benefits of cruciferous vegetable intake, future and ongoing interventions may become more effective by being targeted to those people who will receive the most benefit.