LEGACY: A Cohort of Youth in Families from the Breast Cancer Family Registry

遗产：来自乳腺癌家庭登记处的一群年轻人

• 批准号: 8408766
• 负责人: ESTHER M. JOHN
• 金额: $ 72.88万
• 依托单位: CANCER PREVENTION INSTIT OF CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-18 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8408766
• 关键词: Adolescence; Adolescent; Adolescent Development; Adult; Affect; Age; Age at Menarche; Behavior; Biological Markers; Body Composition; Body Size; Breast; Breast Cancer Prevention; Breast Cancer Risk Factor; Characteristics; Child; Childhood; Clinical; Collection; DNA Methylation; Data; Daughter; Development; Diet; Enrollment; Environment; Epidemiologic Studies; Epidemiology; Epigenetic Process; Exposure to; Family; Family history of; Funding; Genes; Genetic; Genomics; Growth; Health; Individual; Insulin; International; Intervention; Ionizing radiation; Knowledge; Leptin; Life; Life Style; Malignant Neoplasms; Mammary Gland Parenchyma; Measures; Mediating; Melatonin; Molecular; Mothers; Mutation; Names; Pathway interactions; Pattern; Physical activity; Play; Predisposition; Prevention program; Prevention strategy; Recording of previous events; Recruitment Activity; Resources; Risk; Risk Factors; Risk Reduction; Role; Time; Translations; Vitamin D; Woman; Youth; aged; biopsychosocial; breast cancer family; breast cancer family registry; cancer risk; cohort; early life exposure; follow-up; genetic epidemiology; girls; lifestyle factors; malignant breast neoplasm; novel; nutrition; offspring; prevent; prospective; psychosocial; psychosocial adjustment; public health relevance; risk perception

DESCRIPTION (provided by applicant): The identification of risk factors for breast cancer has tremendous clinical importance. One of the strongest risk factors is a family history of breast cancer. Most studies have focused on genetics and lifestyle factors in adult women. However, there is growing evidence that young girls may be particularly sensitive to exposures that either initiate or protect against breast cancer. These include ionizing radiation exposure, childhood and adolescent growth, body composition, and physical activity. It remains unknown whether effects of early life and childhood exposures are greater in individuals with a family history of breast cancer (BCFH). Studies on individuals with a family history of cancer have been of great value in the identification of genetic alterations that play a role in cancer, not only in the familial setting, but more generally in sporadic cancer as well; similarly, familial clustering is also likely associated with clustering of risk factors influenced by both genes and environment, as well as clustering of health-related behaviors, and may therefore be a powerful setting in which to identify factors important in both familial and sporadic breast cancer. We propose to establish a cohort of 450 girls aged 6-13 years who are the offspring of women enrolled in the Breast Cancer Family Registry (BCFR), and 450 girls from families without breast cancer. The youth cohort, named LEGACY (Lessons in Epidemiology and Genetics of Adult Cancer from Youth), will be followed prospectively, with repeated data and biospecimen collection at 6-month intervals. The objectives are to 1) study prospectively the association of pubertal development (onset and tempo of breast development), age at menarche, and breast tissue characteristics over time with childhood measures of body size, growth, lifestyle factors (physical activity, diet, vitamin D), built environment, and selected biomarkers of exposure, and to assess whether these associations are modified by BCFH; 2) assess the association of childhood exposures with genomic DNA methylation and changes in genomic DNA methylation, and assess whether genomic DNA methylation levels are modified by BCFH; and 3) evaluate longitudinally how psychosocial adjustment and behaviors of girls from breast cancer families differ from those of girls from families without breast cancer. Unlike any other youth cohort, the LEGACY cohort is unique in that it will be enriched with girls at increased breast cancer risk, given their family history, and covering a wide spectrum of risk. It is currently not known how young girls at increased risk can lower their risk, how they adapt to their familial risk, and how such familial risk impacts their behaviors throughout development. Understanding these relations is necessary for the successful translation of early-life exposure information into health-promoting and breast cancer-preventing behaviors during childhood and adolescence. LEGACY will provide a rich resource for molecular and biomarker studies in young girls that will inform our understanding of when breast cancer susceptibility begins, whether it is influenced by modifiable determinants, and how it impacts psychosocial adjustment and behaviors.

描述（由申请人提供）：乳腺癌危险因素的识别具有巨大的临床重要性。最强的危险因素之一是乳腺癌家族史。大多数研究都集中在成年女性的遗传和生活方式因素上。然而，越来越多的证据表明，年轻女孩可能对引发乳腺癌或预防乳腺癌的暴露特别敏感。这些包括电离辐射暴露、儿童和青少年成长、身体成分和体力活动。对于有乳腺癌家族史 (BCFH) 的个体，早期生活和儿童时期暴露的影响是否更大仍不清楚。对有癌症家族史的个体进行的研究对于识别在癌症中发挥作用的基因改变具有重要价值，不仅在家族环境中，而且更普遍地在散发性癌症中也是如此；同样，家族聚类也可能与受基因和环境影响的风险因素聚类以及健康相关行为聚类相关，因此可能是识别家族性和散发性乳腺癌重要因素的有力环境。我们建议建立一个由 450 名 6-13 岁女孩组成的队列，这些女孩是在乳腺癌家庭登记处 (BCFR) 登记的女性的后代，以及 450 名来自无乳腺癌家庭的女孩。该青年队列名为 LEGACY（青年成人癌症流行病学和遗传学课程），将进行前瞻性跟踪，每 6 个月重复一次数据和生物样本收集。目标是 1) 前瞻性研究青春期发育（乳房发育的开始和速度）、初潮年龄和乳房组织特征随时间的变化与儿童时期的体型、生长、生活方式因素（体力活动、饮食、维生素 D）、建筑环境和选定的暴露生物标志物的关系，并评估这些关联是否会被 BCFH 改变； 2) 评估童年暴露与基因组DNA甲基化和基因组DNA甲基化变化的关联，并评估BCFH是否改变基因组DNA甲基化水平； 3) 纵向评估乳腺癌家庭女孩的心理社会调整和行为与非乳腺癌家庭女孩的心理社会调整和行为有何不同。与任何其他青年队列不同，LEGACY 队列的独特之处在于，考虑到她们的家族史，该队列将包含乳腺癌风险增加的女孩，并涵盖广泛的风险。目前尚不清楚风险较高的年轻女孩如何降低风险，她们如何适应家庭风险，以及这种家庭风险如何影响她们在整个发育过程中的行为。了解这些关系对于将生命早期暴露信息成功转化为儿童和青少年时期的健康促进和乳腺癌预防行为是必要的。 LEGACY 将为年轻女孩的分子和生物标志物研究提供丰富的资源，帮助我们了解乳腺癌易感性何时开始、是否受到可改变的决定因素的影响，以及它如何影响心理社会调整和行为。