LEGACY: A cohort of youth in families from the Breast Cancer Family Registry

描述（由申请人提供）：乳腺癌风险因素的识别具有巨大的临床意义。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学和生活方式因素上。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照射、儿童和青少年的成长、身体成分和体育活动。目前尚不清楚早期生活和儿童期暴露的影响是否在有乳腺癌家族史（BCFH）的个体中更大。对具有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方面具有重要价值，不仅在家族背景中，而且更普遍地在散发性癌症中;类似地，家族聚集也可能与受基因和环境影响的风险因素的聚集以及与健康相关的行为的聚集有关，因此可能是一个强有力的环境，在其中确定在家族性和散发性乳腺癌中重要的因素。我们建议建立一个由450名6-13岁的女孩组成的队列，这些女孩是乳腺癌家庭登记处（BCFR）登记的妇女的后代，另外450名女孩来自没有乳腺癌的家庭。将对名为LEGACY（青年成人癌症流行病学和遗传学课程）的青年队列进行前瞻性随访，每隔6个月重复采集数据和生物标本。目的是1）前瞻性研究青春期发育与（乳房发育的开始和克里思）、月经初潮年龄以及随着时间的推移乳房组织特征以及儿童时期的体型、生长、生活方式因素测量（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，并评估这些关联是否被BCFH改变; 2）评估儿童期暴露与基因组DNA甲基化和基因组DNA甲基化变化的相关性，并评估基因组DNA甲基化水平是否被BCFH改变; 3）纵向评估来自乳腺癌家庭的女孩与来自非乳腺癌家庭的女孩的心理社会适应和行为有何不同。与任何其他青年队列不同，LEGACY队列的独特之处在于，它将增加乳腺癌风险增加的女孩，考虑到她们的家族史，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，如何适应家庭风险，以及这种家庭风险如何影响他们在整个发展过程中的行为。了解这些关系是必要的成功转化为健康促进和预防乳腺癌的行为在童年和青春期的早期生活暴露信息。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，它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。

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.