Energy Homeostasis and Cancer: Biomarkers and Lifestyles

能量稳态和癌症：生物标志物和生活方式

• 批准号: 6815891
• 负责人: CHARLES E MATTHEWS
• 金额: $ 13.17万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-29 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6815891
• 关键词: adenomatous polyps; bioenergetics; biomarker; body composition; breast neoplasms; caloric dietary content; cancer risk; exercise; gene environment interaction; genetic polymorphism; genetic susceptibility; homeostasis; human data; insulin; insulinlike growth factor; leptin; lifestyle; neoplasm /cancer epidemiology; nutrition related tag

DESCRIPTION (provided by applicant): This career development plan provides a roadmap for the candidate and his mentors to follow in filling gaps in his training that will assist him in achieving independence as a cancer researcher. New knowledge and skills in molecular/genetic epidemiology obtained in the training portion of this award will be applied directly to research examining genetic susceptibility, lifestyle, and cancer risk. Recognition that adipose tissue is both an energy reservoir and a source of proteins with endocrine functions (adipokines), suggests that these proteins, and the genes controlling them, are part of the homeostatic control mechanisms that regulate cell growth. To advance our understanding of the role of energy homeostasis and cancer, epidemiologic studies examining the role of genes involved in energy regulation in humans, as well as the interactions of these exposures with lifestyle factors associated with energy balance are needed. Accordingly, the four aims of this research are as follows. In a case-control study of breast cancer (N=2,500), Aim 1 will examine the effect of polymorphisms in genes involved in energy homeostasis (insulin, IGF-1, leptin, and adiponectin), and Aim 2 will examine gene-environment interactions between these genes and lifestyle factors associated with energy balance (physical activity, energy intake, body size). In a case-control study of adenomatous polyps (N=1,400), Aim 3 will examine the effect of lifestyle factors associated with energy balance (as above), and (Aim 4) will examine the effect of polymorphisms in genes involved in energy homeostasis (as above). Primary research support will come from existing molecular epidemiology studies of the candidate's mentor. Resources from this award will support genotyping of adipokines not originally examined in these studies. This work will extend our understanding of links between energy homeostasis and cancer, as well as interactions between genetic susceptibility, lifestyle factors, and cancer. This work will also serve as the basis for submission of competitive R01 proposals by the candidate in latter years of this award.

描述（由申请人提供）：这项职业发展计划为候选人及其导师提供了路线图，以填补他的培训空白，这将有助于他实现独立的癌症研究员。 在该奖项的培训部分获得的分子/遗传流行病学的新知识和技能将直接应用于研究遗传易感性，生活方式和癌症风险的研究。 认识到脂肪组织既是能量库，又是具有内分泌功能（脂肪因子）的蛋白质的来源，这表明这些蛋白质和控制它们的基因是调节细胞生长的稳态控制机制的一部分。 为了促进我们对能量稳态和癌症作用的理解，需要研究与人类能量调节相关的基因作用的流行病学研究，以及这些暴露与与能量平衡相关的生活方式因素的相互作用。 因此，这项研究的四个目标如下。 在一项乳腺癌的病例对照研究中（n = 2,500），AIM 1将检查与能量稳态有关的基因中多态性的影响（胰岛素，IGF-1，瘦素和脂联素），而AIM 2将检查这些基因和能量平衡之间的基因 - 环境相互作用（物理能量的能量，体力，体现物质，体积），体积，体积，体积，体积，体积，体积。 在一项对腺瘤息肉的病例对照研究（n = 1,400），AIM 3将检查与能量平衡相关的生活方式因素的影响（如上所述），并且（AIM 4）将研究涉及能量稳态基因的多态性的影响（如上）。 主要的研究支持将来自候选人导师的现有分子流行病学研究。 该奖项中的资源将支持这些研究最初未检查的脂肪因子的基因分型。 这项工作将扩展我们对能量稳态与癌症之间的联系，以及遗传易感性，生活方式因素和癌症之间的相互作用。 这项工作还将作为该奖项后期候选人提交竞争性R01提案的基础。