Breast and Other Cancers in the California Teachers Cohort

描述(由申请人提供)：在过去十年中，三种癌症风险因素的重大变化正在改变女性癌症风险的概况。加州教师研究(CTS)是一项前瞻性队列研究，自1995年以来一直积极跟踪调查133,479名加州公立学校女性专业人员的癌症发病率和其他结果，该研究理想地评估身体活动减少、肥胖增加和阿司匹林使用量增加的社会转型如何影响乳腺癌和其他癌症的风险。CTS是关于这些重要的、可修改的癌症风险因素的生命过程中暴露数据的独特储存库。我们的三个目标是解决这些不断变化的暴露与乳腺癌总体风险之间的关系；由激素受体状态、HER-2状态、组织学和分期定义的乳腺癌亚型；以及由肿瘤位置或组织学定义的其他癌症。对于乳腺癌，将通过对关键机制途径(特别是炎症、免疫功能和胰岛素抵抗途径)中基因的单核苷酸多态(SNPs)以及来自全基因组关联研究的高度显著的复制SNPs进行基因分型来评估基因与环境的相互作用。在目标1中，我们试图更好地了解体力活动如何降低乳腺癌风险，调查与健康或运动能力有关的基因变异是否与年龄和新近定义的体力活动模式相互作用，以及与体力活动的任何关联是否被其他环境或遗传风险因素改变。我们还研究了在女性的一生中，身体脂肪和肥胖(目标2)和阿司匹林使用(目标3)的终生和变化模式如何影响女性乳腺癌、子宫内膜癌、卵巢癌或结肠癌的总体风险和亚型，调查效果改变，以及对于乳腺癌，基因-环境相互作用。为了实现这些目标，我们将继续我们目前对癌症和其他结果的跟踪，这些结果链接到数据库，这些数据库捕获了加州居民中100%的这些终点。我们将收集和更新与时间相关的接触数据，以拓宽我们现有的从青少年到老年的关键接触信息。我们将扩大乳腺癌病例和对照的血液采集，采用新的采集方法，以确保高参与度，并建立新的科学合作，以充分利用这一生物样本资源。我们将继续使用统计方法来分析癌症的关键病因预测因素，这些方法可以解释缺失的数据和暴露中的长期变化，并将高维遗传数据纳入现有模型。公共卫生相关性：在体力活动、肥胖和阿司匹林使用方面经历了十年的深刻转变后，这些目标的成功完成将使人们能够评估这些变化对女性癌症发病率的人口影响，并提供对乳腺癌基因和暴露的相互作用的洞察。这项应用侧重于主要女性癌症的病因学，并强调常见的、可改变的行为风险因素，以促进未来全人群的癌症预防工作。 公共卫生相关性： 加州教师的研究跨越了十多年来女性健康行为的深刻转变，包括越来越多的身体不活动、肥胖和阿司匹林的使用。通过研究这些常见的、可改变的风险因素如何与其他环境和遗传风险因素相互作用，影响女性乳腺癌和其他癌症的发展，这项研究将提供关键的新知识，作为在全人口范围内造福女性的行为公共卫生干预的基础。

DESCRIPTION (provided by applicant): Major shifts in three cancer risk factors over the past decade are changing the profile of women's cancer risks. The California Teachers Study (CTS), a prospective cohort study that has actively followed 133,479 female California public school professionals for incidence of cancer and other outcomes since 1995, is ideally poised to evaluate how the societal transitions of decreasing physical activity, increasing obesity, and increasing aspirin use affect risk of breast and other cancers. The CTS is a unique repository of exposure data over the life course on these important, modifiable cancer risk factors. Our three aims address associations between these shifting exposures and risk for breast cancer overall; breast cancer subtypes defined by hormone receptor status, HER-2 status, histology and stage; and other cancers, with subtypes defined by tumor location or histology. For breast cancer, gene-environment interactions will be assessed by genotyping single nucleotide polymorphisms (SNPs) in genes in key mechanistic pathways (particularly in inflammation, immune function, and insulin resistance pathways), as well as highly significant, replicated SNPs from genome-wide association studies. In Aim 1, we seek to understand better how physical activity reduces breast cancer risk, investigating whether variation in genes involved in fitness or athletic ability interacts with physical activity patterns defined by age and recency, and whether any associations with physical activity are modified by other environmental or genetic risk factors. We also examine how lifelong and changing patterns of body fat and obesity (Aim 2) and aspirin use (Aim 3), over a woman's lifespan influence women's breast, endometrial, ovarian or colon cancer risk overall and by subtype, investigating effect modification, and, for breast cancer, gene-environment interactions. To accomplish these aims, we will continue our current follow-up for cancer and other outcomes, which link to databases that capture 100% of these endpoints among California residents. We will collect and update time-dependent exposure data to broaden our existing information on key exposures from teenage years to old age. We will expand blood collection among breast cancer cases and controls, employing new collection approaches to ensure high participation and forging new scientific collaborations to fully utilize this biospecimen resource. We will continue analyzing key etiologic predictors of cancer using statistical approaches that account for missing data and secular changes in exposures and incorporate high-dimensional genetic data into existing models. Public Health Relevance: Successful completion of these aims, following a decade of profound transition in physical activity, obesity, and aspirin use, will permit evaluation of the population impact of these changes on women's cancer incidence, and provide insight into the interplay of genes and exposures for breast cancer. This application focuses on the etiology of major women's cancers and emphasizes common, modifiable, behavioral risk factors in ways that can facilitate future population-wide cancer prevention efforts. PUBLIC HEALTH RELEVANCE: The California Teachers Study spans more than a decade of profound transitions in women's health behaviors, including increasing physical inactivity, obesity, and aspirin use. By examining how these common, modifiable risk factors interact with other environmental and genetic risk factors to influence development of breast and other cancers in women, this study will provide critical new knowledge that can serve as the basis for behavioral public health interventions that benefit women on a population-wide scale.