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

描述(由申请人提供)： 项目摘要/摘要流行病学研究有大量证据表明，早期生活因素在成人癌症的病因中起着重要作用。特别是，早年的体型--包括童年和青春期的出生体重和肥胖--一直与成年后患上几种常见癌症的风险有关。目前，这些关联背后的潜在机制尚不清楚；然而，胰岛素样生长因子(IGF)轴与癌症的发生和发展有关，它代表了一种生物途径，可以提供统一的解释。在这项应用中，我们建议评估儿童和青春期的出生体重和肥胖是否对成年后IGF-I和IGFBP-3的循环水平有长期影响，以及IGF-I和IGFBP-3基因的共同变异是否与早期身体大小的测量有关。我们将利用之前从护士健康研究(NHS)的4200多名参与者收集的问卷数据、血液和颊细胞样本。这些妇女的血浆IGF-I和IGFBP-3水平以及IGF基因数据已经可用。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岁时体重指数的横断面关系。此外，我们还将检查IGF多态和单倍型与早期体重的关系。NHS是解决这些问题的独特资源，因为它汇集了关于早期生活因素、循环中的IGF浓度、IGF基因型和其他潜在混杂因素的高质量数据，适用于大量女性。这将是迄今为止关于早期生命体型和IGF途径的最大规模和最全面的研究。这项拟议的研究将有助于阐明流行病学研究(包括我们自己的研究)中观察到的早期身体尺寸与成年后患癌症风险之间的联系的生物学机制。从公共卫生的角度来看，阐明这些机制对于确定和制定有效的癌症预防策略是很重要的，特别是因为身体尺寸是一个可改变的危险因素。 公共卫生相关性： 项目叙述儿童期和青春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途径。这项应用旨在评估儿童和青春期出生体重和肥胖是否对成年后循环IGF水平有长期影响，以及IGF的遗传变异是否与这些体型测量有关，使用护士健康研究的数据。澄清早期生活因素与成人癌症风险之间的关系的机制对于确定有效的预防策略非常重要，特别是因为身体大小是一个可改变的风险因素。

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.