Gene-Nutrient Interactions and Breast Cancer

描述（由申请人提供）：Susan Steck-Scott，博士，公共卫生硕士，RD是查佩尔山的北卡罗来纳州大学营养系的研究助理教授。 通过这个职业发展奖，她正在寻求分子流行病学和癌症生存的培训，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，罗伯特密立根，迈克尔谢尔和弗雷德赖特博士是在各自领域的知名调查员，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、致癌作用、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。 该培训将帮助候选人在癌症研究界发展独特的利基，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。 该奖项的主要重点是一个研究项目，以检查十字花科蔬菜摄入量和乳腺癌预防，复发和生存代谢酶编码基因多态性之间的相互作用。 拟议的研究利用了饮食数据，尿液和血液样本，这些样本来自一项已经进行的基于人群的病例对照研究，即长岛乳腺癌研究项目，Gammon博士是该项目的主要研究者。 目前正在对乳腺癌受试者的复发和生存状态进行随访。 本研究的具体目的是：（1）在对照组中检测十字花科蔬菜摄入量、尿中异硫氰酸盐（ITC）排泄量与GSTM 1、GSTT 1和GSTP 1基因多态性之间的关系，以确定GSTM 1、GSTT 1和/或GSTP 1基因型是否导致ITC尿排泄量增加;（2）通过大样本病例对照研究，探讨十字花科蔬菜摄入量与GSTM 1、GSTT 1、GSTP 1和GSTP 1A 1基因多态性之间的交互作用及其与乳腺癌发病风险的关系;以及3）在病例的随访研究中检查与乳腺癌复发和生存相关的相互作用。 这项研究代表了一个独特的机会，以检查十字花科蔬菜是否正在修改遗传多态性在乳腺癌预防，复发和生存中的作用。 通过确定那些可能在遗传上更容易受到十字花科蔬菜摄入益处影响的个体，未来和正在进行的干预措施可能会变得更有效，因为这些干预措施针对的是那些将获得最大益处的人。

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.