Breast and Other Cancers in the California Teachers Cohort

描述（由申请人提供）：在过去十年中，三个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，该研究积极跟踪了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，该研究理想地评估了体力活动减少、肥胖增加和阿司匹林使用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、可改变的癌症风险因素的生命过程中暴露数据的独特存储库。我们的三个目标解决了这些变化的暴露与乳腺癌风险之间的关联;乳腺癌亚型由激素受体状态，HER-2状态，组织学和分期定义;其他癌症，亚型由肿瘤位置或组织学定义。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性（SNP）以及来自全基因组关联研究的高度显著、重复的SNP进行基因分型来评估基因-环境相互作用。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，调查参与健身或运动能力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所改变。我们还研究了如何终身和不断变化的模式的身体脂肪和肥胖（目标2）和阿司匹林的使用（目标3），在一个女人的寿命影响妇女的乳腺癌，子宫内膜癌，卵巢癌或结肠癌的风险整体和亚型，调查效果修改，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的癌症和其他结果的随访，这些结果与数据库相链接，这些数据库在加州居民中捕获100%的这些终点。我们将收集和更新随时间变化的暴露数据，以扩大我们现有的关于从青少年到老年的主要暴露的信息。我们将扩大乳腺癌病例和对照组的血液采集，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标本资源。我们将继续使用统计方法分析癌症的关键病因学预测因子，这些方法可以解释缺失数据和暴露的长期变化，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经历了十年的深刻转变之后，这些目标的成功完成将允许评估这些变化对妇女癌症发病率的人口影响，并提供对基因和乳腺癌暴露的相互作用的深入了解。该应用程序侧重于主要女性癌症的病因学，并强调常见的，可改变的，行为风险因素的方式，可以促进未来人口范围内的癌症预防工作。 公共卫生相关性： 这项加州教师研究跨越了十多年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，以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，这些知识可以作为行为公共卫生干预的基础，使女性受益。

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.