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: 8788253
• 负责人: Angela R. Bradbury
• 金额: $ 57.86万
• 依托单位: RESEARCH INST OF FOX CHASE CAN CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-10 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8788253
• 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; Genomic DNA; 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; built environment; cancer risk; cohort; early life exposure; follow-up; genetic epidemiology; girls; lifestyle factors; malignant breast neoplasm; methylation pattern; 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.

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。其中一个最大的风险因素是乳腺癌的家族史。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或预防乳腺癌的暴露特别敏感。这些因素包括电离辐射暴露、儿童和青少年成长、身体构成和身体活动。对于有乳腺癌家族史（BCFH）的个体，早期生活和儿童时期接触乳腺癌的影响是否更大，目前尚不清楚。对有癌症家族史的个体的研究在确定在癌症中起作用的基因改变方面具有重要价值，不仅在家族环境中，而且更普遍地在散发性癌症中；同样，家族聚类也可能与受基因和环境影响的风险因素的聚类以及与健康有关的行为的聚类有关，因此可能是确定家族性和散发性乳腺癌重要因素的有力环境。我们建议建立一个队列，包括450名6-13岁的女孩，她们是乳腺癌家庭登记处（BCFR）登记的妇女的后代，以及450名来自无乳腺癌家庭的女孩。青年队列，命名为LEGACY（成人癌症流行病学和遗传学课程，来自青年），将进行前瞻性随访，每隔6个月重复收集数据和生物标本。目的是：(1)前瞻性研究青春期发育（乳房发育的开始和速度）、月经初潮年龄和乳腺组织特征与儿童时期的体型、生长、生活方式因素（身体活动、饮食、维生素D）、建筑环境和选定的暴露生物标志物之间的关系，并评估这些关系是否被BCFH改变；2)评估儿童暴露与基因组DNA甲基化和基因组DNA甲基化变化的关系，评估BCFH是否会改变基因组DNA甲基化水平；3)纵向评价乳腺癌家庭女孩与非乳腺癌家庭女孩的心理社会适应和行为差异。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，它将丰富乳腺癌风险增加的女孩，并涵盖广泛的风险。目前尚不清楚风险增加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展过程中的行为。了解这些关系对于将早期生活暴露信息成功转化为儿童和青少年时期促进健康和预防乳腺癌的行为是必要的。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，这将使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适应和行为。

项目成果

Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients.

通过研究侵入性乳腺癌患者中个体内DCIS异质性来鉴定高攻击性的DCIS亚组。

• DOI: 10.1371/journal.pone.0100488
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Pape-Zambito D;Jiang Z;Wu H;Devarajan K;Slater CM;Cai KQ;Patchefsky A;Daly MB;Chen X
• 通讯作者: Chen X