Body Size in Early Like and Insulin-Like Growth Factor in Adulthood

早期体型大小和成年期胰岛素样生长因子

• 批准号: 7876784
• 负责人: Heather Joanne Baer
• 金额: $ 8.9万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7876784
• 关键词: Address; Adolescence; Adult; Affect; Age; Apoptosis; Area; Binding Proteins; Birth Weight; Blood; Body Size; Body mass index; Cell Proliferation; Cells; Cheek structure; Childhood; Colorectal Cancer; Data; Data Quality; Development; Environment; Epidemiologic Studies; Etiology; Future; Genes; Genetic Polymorphism; Genetic Variation; Genotype; Grant; Growth and Development function; Haplotypes; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Life; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Measures; Nurses' Health Study; Obesity; Ovarian; Participant; Pathway interactions; Plasma; Play; Postmenopause; Premenopause; Prevention strategy; Principal Investigator; Prostate; Public Health; Questionnaires; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Shapes; Somatomedins; Time; Variant; Woman; abstracting; cancer prevention; cancer risk; career development; cost effective; in utero; malignant breast neoplasm; modifiable risk; public health relevance

DESCRIPTION (provided by applicant): PROJECT SUMMARY/ABSTRACT There is substantial evidence from epidemiologic studies indicating that early life factors play an important role in the etiology of adult cancers. In particular, body size in early life - including birth weight and adiposity during childhood and adolescence - consistently has been associated with risk of several common cancers in adulthood. Currently, the underlying mechanisms behind these associations are not understood; however, the insulin-like growth factor (IGF) axis, which has been implicated in cancer development and progression, represents a biologic pathway that could provide a unifying explanation. In this application, we propose to evaluate whether birth weight and adiposity during childhood and adolescence have long-term influences on circulating levels of IGF-I and IGFBP-3 in adulthood, and whether common variation in the IGF-I and IGFBP-3 genes is related to these measures of body size in early life. We will utilize previously collected questionnaire data, blood, and cheek cell samples from over 4200 participants in the Nurses' Health Study (NHS). Plasma levels of IGF-I and IGFBP-3 and IGF genotype data for these women are already available. We will assess the cross-sectional relations of IGF-I and IGFBP-3 levels with birth weight, body shape at ages 5 and 10, and body mass index at age 18. In addition, we will examine associations of IGF polymorphisms and haplotypes with body size in early life. The NHS represents a unique resource for addressing these questions, given that it brings together high-quality data on early life factors, circulating IGF concentrations, IGF genotype, and other potential confounding factors for a large number of women. This will be the largest and most comprehensive study of body size in early life and the IGF pathway to date. The proposed study will help to elucidate the biologic mechanisms underlying associations observed in epidemiologic studies, including our own, between body size in early life and risk of cancer in adulthood. Clarifying these mechanisms is important from a public health standpoint to identify and develop effective strategies for cancer prevention, particularly since body size is a modifiable risk factor. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE Birth weight and adiposity during childhood and adolescence have been associated with risk of several common cancers in adulthood, and the insulin-like growth factor (IGF) axis represents a potential biologic pathway. This application aims to evaluate whether birth weight and adiposity during childhood and adolescence have long-term influences on circulating IGF levels in adulthood and whether genetic variation in IGF is related to these body size measures, using data from the Nurses' Health Study. Clarifying the mechanisms that explain the associations of early life factors with adult cancer risk is important to identify effective prevention strategies, particularly since body size is a modifiable risk factor.

描述（由申请人提供）： 流行病学研究的大量证据表明，早期生活因素在成人癌症的病因学中起着重要作用。特别是，生命早期的体型-包括出生体重和儿童和青少年时期的肥胖-一直与成年后几种常见癌症的风险相关。目前，这些关联背后的潜在机制尚不清楚;然而，与癌症发展和进展有关的胰岛素样生长因子（IGF）轴代表了一种生物学途径，可以提供统一的解释。在本申请中，我们建议评估儿童期和青春期的出生体重和肥胖是否对成年期IGF-I和IGFBP-3的循环水平具有长期影响，以及IGF-I和IGFBP-3基因的常见变异是否与生命早期的这些身体大小测量相关。我们将利用以前收集的问卷数据，血液和脸颊细胞样本，从超过4200名参与者在护士健康研究（NHS）。这些妇女的IGF-I和IGFBP-3的血浆水平和IGF基因型数据已经可用。我们将评估IGF-I和IGFBP-3水平与出生体重、5岁和10岁时的体型以及18岁时的体重指数的横截面关系。此外，我们还将研究IGF多态性和单倍型与早期生活中体型的关系。NHS代表了解决这些问题的独特资源，因为它汇集了大量女性的早期生活因素，循环IGF浓度，IGF基因型和其他潜在混杂因素的高质量数据。这将是迄今为止最大和最全面的关于生命早期体型和IGF途径的研究。这项拟议的研究将有助于阐明流行病学研究中观察到的潜在关联的生物学机制，包括我们自己的研究，早期生活中的身体大小和成年后患癌症的风险之间的关系。从公共卫生的角度来看，澄清这些机制对于确定和制定有效的癌症预防策略非常重要，特别是因为体型是一个可改变的风险因素。 公共卫生关系： 儿童和青少年时期的出生体重和肥胖与成年后几种常见癌症的风险有关，胰岛素样生长因子（IGF）轴代表了一种潜在的生物学途径。该应用旨在评估儿童和青少年时期的出生体重和肥胖是否对成年后的循环IGF水平产生长期影响，以及IGF的遗传变异是否与这些身体尺寸测量相关，使用来自护士健康研究的数据。阐明解释早期生活因素与成人癌症风险之间关系的机制对于确定有效的预防策略非常重要，特别是因为体型是一个可改变的风险因素。