Genes, Hormones and Breast Cancer Risk

基因、激素和乳腺癌风险

• 批准号: 7918112
• 负责人: VERONICA WENDY SETIAWAN
• 金额: $ 13.08万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-18 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7918112
• 关键词: Affect; African American; Age; Age at Menarche; Alcohol consumption; Anabolism; Androgens; Androstenedione; Binding Proteins; Biological Availability; Biometry; Breast; Breast Cancer Risk Factor; CYP11A1 gene; CYP17A1 gene; CYP19A1 gene; Candidate Disease Gene; Characteristics; Cohort Studies; Collaborations; Complex; Cross-Sectional Studies; Diet; Doctor of Philosophy; Educational workshop; Effectiveness; Environment; Environmental Risk Factor; Epidemiology; Estradiol; Estrogens; Estrone; Ethnic group; Exposure to; Fatty acid glycerol esters; Fiber; First Births; Genes; Genetic; Genetic Determinism; Genetic Predisposition to Disease; Genetic Variation; Genome; Genomics; Goals; Gonadal Steroid Hormones; Growth Factor; HSD17B2 gene; Haplotypes; Hawaiian population; Head; High Risk Woman; Hormones; Individual; Institutes; Intake; Investigation; Japanese Population; K-Series Research Career Programs; Knowledge; Latina; Life Style; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Menopause; Mentors; Pathway interactions; Physical activity; Plasma; Population; Postmenopause; Prevention strategy; Preventive Medicine; Qualifying; Reproductive History; Research; Research Personnel; Research Project Grants; Research Proposals; Resources; Risk; Risk Factors; Role; Sex Hormone-Binding Globulin; Smoking; Statistical Models; Structure; Testosterone; Training; Underserved Population; United States; Variant; Woman; Work; base; cancer epidemiology; cancer genetics; cancer risk; carcinogenesis; career development; cohort; dehydroepiandrosterone; design; experience; gene environment interaction; interest; malignant breast neoplasm; novel; parity; planetary Atmosphere; population based; post-doctoral training; racial and ethnic; reproductive; skills; soy; steroid hormone biosynthesis; trait

DESCRIPTION (provided by applicant): Dr. Wendy Setiawan received her Ph.D. in epidemiology from UCLA in 2002. She completed a year of postdoctoral training at Harvard and is currently at the Department of Preventive Medicine at USC where she is part of the highly interactive population/cancer genetics group headed by Dr. Brian E. Henderson. The goal of this career development award is to provide Dr. Setiawan with the knowledge and necessary skills to become an independent cancer researcher. A combination of research project, structured courses, seminars, workshops, and mentoring has been designed to accomplish this goal. Two highly qualified and experienced mentors with relevant expertise, Dr. Henderson (cancer epidemiology) and Dr. Duncan Thomas (biostatistics and genetics), will supervise her training. The scientific culture and collaborative research atmosphere in the department provide an ideal environment for the candidate's academic career development. The objective of Dr. Setiawan's research project is to identify environmental and genetic determinants of circulating endogenous sex-steroid hormone levels, because there are substantial inter-individual variations in circulating hormone levels and postmenopausal women with elevated estrogens and androgens are at an increased risk of breast cancer. A cross-sectional study of healthy postmenopausal women from the Multiethnic Cohort Study (MEC) will be conducted to 1) determine whether known/potential breast cancer risk factors are associated with plasma hormone levels, 2) characterize genetic variation of estrogen biosynthesis genes (CYP11A, CYP17, CYP19, HSD3B1, HSD3B2, HSD17B1, HSD17B2, and SHBG) using a two-pronged approach (putative functional variants and inferred haplotypes) and evaluate these in relation to hormone levels; 3) develop and implement a Bayesian hierarchical statistical model that allows for an efficient and pathway-driven examination of multiple gene-gene and a priori gene-environment interactions in influencing hormone levels. The unique feature of the proposed study is that it integrates a large multiethnic population-based study, cutting edge genomic resources, and novel statistical approaches to identify genetic and environmental factors responsible for inter-individual variations in endogenous hormone levels. Identification of these factors is important to understand the mechanisms by which they could influence breast cancer risk and ultimately to identify high-risk women for prevention strategies.

描述（由申请人提供）：Wendy Setiawan博士获得博士学位。她于2002年获得加州大学洛杉矶分校（UCLA）的流行病学。该职业发展奖的目标是为Setiawan博士提供成为独立癌症研究员的知识和必要技能。研究项目，结构化课程，研讨会，研讨会和指导的结合旨在实现这一目标。两位具有相关专业知识的高素质和经验丰富的导师Henderson博士（癌症流行病学）和Duncan Thomas博士（生物统计学和遗传学）将监督她的培训。该部门的科学文化和协作研究氛围为候选人的学术职业发展提供了理想的环境。 Setiawan博士的研究项目的目的是确定循环内源性性类固醇激素水平的环境和遗传决定因素，因为循环激素水平和绝经后妇女的雌激素和雄激素升高的循环激素水平和雄激素升高的妇女存在实质性的差异。 A cross-sectional study of healthy postmenopausal women from the Multiethnic Cohort Study (MEC) will be conducted to 1) determine whether known/potential breast cancer risk factors are associated with plasma hormone levels, 2) characterize genetic variation of estrogen biosynthesis genes (CYP11A, CYP17, CYP19, HSD3B1, HSD3B2, HSD17B1, HSD17B2和SHBG）使用两管齐下的方法（假定的功能变体和推断的单倍型），并根据激素水平评估这些方法； 3）开发和实施一个贝叶斯分层统计模型，该模型允许对多个基因基因和先验基因 - 环境相互作用进行有效且驱动途径驱动的统计模型。拟议的研究的独特特征是，它整合了一项大型基于多种族的研究，最先进的基因组资源以及新型的统计方法，以鉴定负责内源激素水平的个体间变异的遗传和环境因素。这些因素的识别对于了解它们可以影响乳腺癌风险的机制很重要，并最终确定高危女性以预防策略。

项目成果

Menstrual and reproductive factors and risk of renal cell cancer in the Multiethnic Cohort.

• DOI: 10.1158/1055-9965.epi-08-0790
• 发表时间: 2009-01
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Setiawan VW;Kolonel LN;Henderson BE
• 通讯作者: Henderson BE

Alcohol consumption and endometrial cancer risk: the multiethnic cohort.

饮酒和子宫内膜癌风险：多种族队列。

• DOI: 10.1002/ijc.23072
• 发表时间: 2008
• 期刊: International journal of cancer
• 影响因子: 6.4
• 作者: Setiawan,VeronicaWendy;Monroe,KristineR;Goodman,MarcT;Kolonel,LaurenceN;Pike,MalcolmC;Henderson,BrianE
• 通讯作者: Henderson,BrianE

Body size, adult BMI gain and endometrial cancer risk: the multiethnic cohort.

• DOI: 10.1002/ijc.24718
• 发表时间: 2010-01-15
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Park, Sungshim Lani;Goodman, Marc T.;Zhang, Zuo-Feng;Kolonel, Laurence N.;Henderson, Brian E.;Setiawan, Veronica Wendy
• 通讯作者: Setiawan, Veronica Wendy