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.

项目概要 早发性乳腺癌 (BC) 的发病率在全球范围内急剧增加，其中包括美国 增幅最大的是年轻的非西班牙裔黑人 (NHB) 女性。确定可改变的原因 早发 BC 对于减少健康不平等至关重要，这是公共卫生和 BC 预防的首要任务，并且 解决了 NCI 2020 年关于 40 岁以下成人癌症病因学的挑衅性问题之一。 成年期的体力活动是癌症的既定危险因素，而且肿瘤发生的潜伏期较长 表明青春期的体力活动可能在早发 BC 的发展中发挥重要作用。 然而，目前支持这一点的流行病学数据有限，尤其是来自不同种族群体的数据。它 我们必须解决证据基础上的这一重大差距。这项研究的总体目标是阐明 青少年体力活动在早发 BC 的风险和结果中的作用，包括是否 体力活动影响少女和年轻女性的乳腺组织生物标志物。目标 1 (K99) 将评估 青少年体力活动与年轻女性早发 BC 风险和诊断后结果的关系 使用生存建模方法与因果方法相结合，跨越 BC 易感性的连续体， 包括孟德尔随机化和兄弟集分析。该目标将使用来自不同种族的现有数据 基于家庭的 31,640 名女性队列，丰富了 BC 家族史 (BCFH)，其中包括 7,703 名 (1,422 NHB 或西班牙裔）在 50 岁之前诊断出患有 BC 的女性（3,108 名在 40 岁之前诊断出）。目标 2 (K99) 将 确定体力活动是否与青春期女孩 BC 风险的中间标志相关，包括 通过光谱 (OS) 测量乳房发育时间和乳房组织成分 (BTC)。这 Target 将使用两个青少年队列的现有前瞻性数据，其中包括 1,040 名女孩的多种族队列 这对于 BCFH 以及纽约市的 216 名 NHB 和西班牙裔女孩来说是丰富的。目标 3 (R00) 将评估是否 青少年体力活动与青少年乳腺组织的结构和代谢差异有关 40 岁以下的女性，并确定这些改变是否与早发 BC 风险相关。这个目标将是 在独立 R00 阶段通过对 150 名 40 岁以下女性进行病例对照研究完成， 新诊断为 BC 的患者以及 300 名匹配的对照者（样本≥50% NHB 或西班牙裔）。 BTC将以 使用 OS 和乳房 X 线摄影的病例和对照。总而言之，本研究将提供最全面的 迄今为止对青少年体力活动和早发 BC 的评估，这是推动 BC 领域发展所必需的 预防研究的进展，为早期感染风险增加的人群制定新的干预策略 发病的疾病。这项研究将得到分子和遗传学方面的体验和教学培训的补充 流行病学、先进的统计方法、身体活动研究和干预设计以及职业 发展活动。因此，这个 K99/R00 奖项将有助于实现领导一个 研究适合早期生命干预的癌症风险调节因素的独立研究项目。