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: 8041463
• 负责人: ESTHER M. JOHN
• 金额: $ 76.15万
• 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/8041463
• 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; 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. PUBLIC HEALTH RELEVANCE: Focusing on childhood and adolescence is particularly important for developing breast cancer prevention programs as we know that the interplay of modifiable factors such as nutrition, body size, and physical activity is apparent early in life, and that early life patterns have long lasting influence on adult patterns. Knowledge gained from the proposed study will not only be relevant for breast cancer prevention strategies for individuals with a family history of breast cancer families, but also for individuals without a family history. A thorough understanding of perceptions of risk and risk reduction interventions among children and adolescents is critical for the implementation of effective prevention programs that start early in life.

描述（由申请人提供）：鉴定乳腺癌的危险因素具有极大的临床重要性。最强的危险因素之一是乳腺癌的家族史。大多数研究都集中在成年女性的遗传学和生活方式因素上。但是，越来越多的证据表明，年轻女孩可能对启动或预防乳腺癌的暴露特别敏感。这些包括电离辐射暴露，儿童期和青少年生长，身体成分和体育锻炼。乳腺癌家族史（BCFH）患者的早期和儿童期暴露的影响是否更大，尚不清楚。关于癌症家族史的个体的研究在鉴定在癌症中起作用的遗传改变，不仅在家族环境中，而且更普遍地在零星癌中具有重要价值。同样，家族性聚类也可能与受基因和环境影响的危险因素的聚类以及与健康相关行为的聚类有关，因此可能是一个有力的环境，可以在其中识别在家庭和零星乳腺癌中重要的因素。我们建议建立一个由6-13岁的450名女孩组成的队列，这些女性是乳腺癌家庭登记处（BCFR）的女性的后代，以及来自没有乳腺癌的家庭的450名女孩。青年队列将被命名为遗产（年轻人的年轻人的流行病学和成年癌的遗传学课程），并将以6个月的间隔进行重复的数据和生物传播收集。目的是1）前瞻性地研究青春期发展的关联（乳房发育的发作和节奏），初潮的年龄以及随时间的乳房组织特征与儿童时期的体型，生长，生活方式因素（体育活动，饮食，维生素，维生素，维生素， d），建造环境和选择的暴露生物标志物，并评估这些关联是否通过BCFH修改； 2）评估儿童期暴露与基因组DNA甲基化和基因组DNA甲基化变化的关联，并评估基因组DNA甲基化水平是否通过BCFH改变了； 3）纵向评估乳腺癌家庭女孩的社会心理调整和行为与没有乳腺癌的家庭的女孩不同。与其他任何青年队列不同，旧的队列的独特之处在于，鉴于其家族史，它将充满乳腺癌风险增加的女孩，并涵盖广泛的风险。目前，尚不知道处于风险增加的年轻女孩如何降低风险，如何适应家族风险以及这种家庭风险如何影响其整个发展的行为。了解这些关系对于在儿童期和青少年期间成功地转化为早期寿命暴露信息为健康和乳腺癌预防行为是必要的。遗产将为年轻女孩的分子和生物标志物研究提供丰富的资源，这些资源将告知我们对乳腺癌易感性何时开始的理解，是否受到可修改的决定因素的影响，以及它如何影响社会心理调整和行为。 公共卫生相关性：专注于童年和青春期对于制定乳腺癌预防计划尤为重要对成人模式的持久影响。从拟议的研究中获得的知识不仅与具有乳腺癌家族史的人的乳腺癌预防策略有关，而且还与没有家族史的个体有关。对儿童和青少年对风险和降低风险降低风险干预的看法的透彻理解对于实施生命早期开始的有效预防计划至关重要。