Characterizing the role of adolescent physical activity in early onset breast cancer risk for women across the familial risk continuum

描述青少年体力活动在整个家庭风险连续体中女性早发乳腺癌风险中的作用

• 批准号: 10447949
• 负责人: Rebecca D Kehm
• 金额: $ 17.09万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-18 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10447949
• 关键词: Accelerometer; Address; Adolescence; Adolescent; Adult; Affect; Age; Award; Biological Markers; Black race; Body Composition; Body Size; Breast; Breast Cancer Prevention; Breast Cancer Risk Factor; Cancer Etiology; Carcinogens; Case-Control Studies; Color; Communities; Complement; Coupled; Data; Development; Diagnosis; Ethnic Origin; Evaluation; Family; Family Cancer History; Female Adolescents; Genetic; Goals; Habits; Hispanic; Hormones; Incidence; Intervention; Interviewer; Investments; Life; Malignant Neoplasms; Mammary Gland Parenchyma; Mammography; Measures; Mediation; Mendelian randomization; Metabolic; Metabolic Marker; Methods; Modeling; Modification; Molecular Epidemiology; Newly Diagnosed; Not Hispanic or Latino; Onset of illness; Optics; Outcome; Phase; Physical activity; Play; Population; Predisposition; Prevention Research; Prognosis; Questionnaires; Race; Recording of previous events; Recurrence; Reporting; Research; Research Design; Risk; Risk Factors; Role; Sampling; Siblings; Spectrum Analysis; Statistical Methods; Surveys; Testing; Time; Training; Undifferentiated; Woman; adverse outcome; base; black women; breast cancer diagnosis; breast cancer family; cancer prevention; cancer risk; cancer subtypes; career; career development; case control; cohort; digital; early onset; emerging adult; epidemiologic data; evidence base; genetic epidemiology; girls; health equity; health inequalities; insight; malignant breast neoplasm; molecular subtypes; mortality; multi-ethnic; novel; older women; parity; physical inactivity; programs; prospective; public health priorities; racial disparity; racial diversity; routine screening; screening; therapy design; tissue biomarkers; trend; tumor; tumorigenesis; young woman

PROJECT SUMMARY Early onset breast cancer (BC) incidence has increased dramatically worldwide, including in the U.S. where the greatest increase has occurred in young non-Hispanic Black (NHB) women. Identifying the modifiable causes of early onset BC is critical for reducing health inequities, a top priority for public health and BC prevention, and addresses one of the NCI’s 2020 provocative questions on the etiology of cancers in adults under age 40. Physical activity in adulthood is an established risk factor for cancer, and the long latency of tumorigenesis suggests that physical activity in adolescence may play an important role in the development of early onset BC. However, there is currently limited epidemiologic data, especially from racially diverse cohorts, to support this. It is essential that we address this major gap in the evidence-base. The overarching goal of this study is to elucidate the role of adolescent physical activity in the risk of and outcomes from early onset BC, including whether physical activity impacts breast tissue biomarkers in adolescent girls and young women. Aim 1 (K99) will evaluate adolescent physical activity in association with early onset BC risk and outcomes after diagnosis in young women across the continuum of BC susceptibility using survival modeling approaches coupled with causal methods, including Mendelian randomization and sibling set analyses. This aim will use existing data from a racially diverse family-based cohort of 31,640 women that is enriched for BC family history (BCFH) and includes 7,703 (1,422 NHB or Hispanic) women diagnosed with BC before age 50 (3,108 diagnosed before age 40). Aim 2 (K99) will determine if physical activity is associated with intermediate markers of BC risk in adolescent girls, including timing of breast development and breast tissue composition (BTC) measured by optical spectroscopy (OS). This aim will use existing prospective data from two adolescent cohorts, including a multiethnic cohort of 1,040 girls that is enriched for BCFH and a cohort of 216 NHB and Hispanic girls in NYC. Aim 3 (R00) will evaluate if adolescent physical activity is associated with structural and metabolic differences in the breast tissue of young women under age 40 and determine if these alterations are associated with early onset BC risk. This aim will be completed during the independent R00 phase by conducting a case-control study in 150 women under age 40, newly diagnosed with BC, and 300 matched controls (sample ≥50% NHB or Hispanic). BTC will be measured in cases and controls using OS and mammography. Taken together, this study will provide the most comprehensive evaluation of adolescent physical activity and early onset BC to date, which is needed to move the field of BC prevention research forward in developing novel intervention strategies for populations at increased risk of early onset disease. This research will be complemented by experiential and didactic training in molecular and genetic epidemiology, advanced statistical methods, physical activity research, and intervention design, as well as career development activities. This K99/R00 award will thus facilitate the long-term career objective of leading an independent research program studying modifiers of cancer risk that are amenable to early life intervention.

项目摘要 早期发作乳腺癌（BC）发病率在全球范围内急剧增加，包括在美国 年轻的非西班牙裔黑人（NHB）妇女发生了最大的增长。确定可修改的原因 BC早期发作对于减少健康不平等，公共卫生和卑诗省预防的首要任务至关重要，以及 谈到了NCI 2020年关于40岁以下成年人癌症病因的挑衅性问题之一。 成年中的体育活动是癌症的确定危险因素，肿瘤发生的长期潜伏期 表明青少年的体育锻炼可能在早期发作BC的发展中起重要作用。 但是，目前存在有限的流行病学数据，尤其是从大致多样的人群来支持这一点。它 我们必须解决循证库中的这一主要差距。这项研究的总体目标是阐明 青少年体育锻炼在早期发作的风险和结果中的作用，包括是否是否 体育活动会影响青春期女孩和年轻女性的乳房组织生物标志物。 AIM 1（K99）将评估 青少年体育活动与年轻女性诊断后的早期发作风险和结果相关 在BC易感性的连续性中，使用生存模型方法加上因果方法， 包括孟德尔随机化和兄弟姐妹集分析。该目标将使用来自种族多样的现有数据 以家庭历史（BCFH）丰富的31,640名妇女为基础家庭的队列，包括7,703（1,422 NHB或西班牙裔）妇女在50岁之前被诊断出患有BC的妇女（40岁之前被诊断出3,108名）。 AIM 2（K99）将 确定体育锻炼是否与青少年女孩的BC风险中间标记有关，包括 通过光谱法（OS）测得的乳房发育和乳房组织组成（BTC）的时间。这 AIM将使用来自两个青春期队列的现有数据，包括1,040个女孩的多民族队列 这对BCFH和纽约市的216 NHB和西班牙裔女孩的队列丰富了。 AIM 3（R00）将评估是否 青少年的体育活动与幼体组织的结构和代谢差异有关 40岁以下的妇女确定这些改变是否与BC早期发作风险有关。这个目标将是 通过对150名40岁以下的女性进行病例对照研究，在独立R00阶段完成 新诊断为BC和300个匹配的对照（样本≥50％NHB或西班牙裔）。 BTC将在 使用OS和乳房X线摄影的病例和对照。综上所述，这项研究将提供最全面的 迄今为止的青少年体育锻炼和早期发作的评估，这是移动BC领域所需的 预防研究在制定新的干预策略以增加早期风险的新干预策略方面 发作疾病。这项研究将由分子和遗传的专家和教学培训完成 流行病学，高级统计方法，体育活动研究和干预设计以及职业 发展活动。因此，该K99/R00奖将促进领导的长期职业目标 独立研究计划研究癌症风险的修饰符，这些风险适合早期生活干预。