Determinants of breast tissue composition in young women

年轻女性乳房组织成分的决定因素

• 批准号: 8208876
• 负责人: NORMAN F BOYD
• 金额: $ 65.66万
• 依托单位: UNIVERSITY HEALTH NETWORK
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-18 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8208876
• 关键词: 18 year old; 19 year old; Age; Area; Blood; Breast; Breast Cancer Prevention; Breast Cancer Risk Factor; Carcinogens; Computer Assisted; DNA; Data; Environmental Exposure; Epidemiology; Event; Genes; Genetic; Genetic Variation; Genome; Genotype; Goals; Gonadal Steroid Hormones; Growth Factor; Growth and Development function; Height; Heritable Quantitative Trait; Hormonal; Hormones; Image; Incidence; Inherited; Knowledge; Left; Life; Luteal Phase; Magnetic Resonance; Magnetic Resonance Imaging; Mammary Gland Parenchyma; Mammary Tumorigenesis; Mammographic Density; Mammography; Measures; Menopause; Mitogens; Modeling; Mothers; Oral Contraceptives; Output; Pike fish; Predisposition; Pregnancy; Premenopause; Recruitment Activity; Red Cross; Research; Risk; Risk Factors; Sampling; Serum; Sex Hormone-Binding Globulin; Slice; Solid; Somatotropin; Testosterone; Thick; Tissues; Variant; Water; Weight; Woman; Work; age group; aged; density; genetic variant; genome wide association study; girls; malignant breast neoplasm; middle age; prevent; proliferative phase Menstrual cycle; public health relevance; young woman

DESCRIPTION (provided by applicant): The long-term goal of the research proposed here is to generate new knowledge that can be applied to young women to prevent breast cancer. The theoretical Pike model of "breast tissue age", and empirical epidemiological evidence, indicate that the breast is especially susceptible to the effects of carcinogens at early ages, and suggest that strategies of breast cancer prevention will be most effective if started early in life. Motivated by previous work that has shown variations in percent mammographic density (PMD) to be associated with large differences in risk of breast cancer in women of middle age and older, to be highly heritable, and strongly correlated with the water content of the breast as assessed by magnetic resonance (MR), we have examined factors associated with variations in breast tissue in young women using MR. To date we have examined 400 young women (aged 15-30 years), and their mothers. Breast MR has been used to characterize breast tissue in all young women and a random sample of 100 mothers. Mean levels and variation in breast water content were greatest in young women aged 15-18 years, when susceptibility to carcinogens is also greatest. We have found that the breast water content in young women is correlated with their weight and height, suggesting that general measures of growth and development are associated with breast tissue composition. Consistent with a previously described genetic influence, breast water content in young women was also associated with both the breast water content by MR and PMD of their mothers. We also found that blood levels of growth hormone and sex hormone binding globulin in all subjects were associated with breast water content. We thus have evidence that both hormonal and genetic factors influence breast tissue composition in young women. We propose here to recruit additional young women (aged 15-18 years) to add to those already examined, to provide a sample large enough to examine common genetic variation across the genome and the phenotypic features of breast tissue. This sample will also allow us to re-examine the associations of hormones and growth factors with breast tissue composition in this age group. The work completed to date has shown the feasibility of recruiting the number of young women required to achieve these aims. We will replicate results from the genome wide association study in young women in premenopausal women from whom DNA and collected and mammograms have been collected. To the best of our knowledge this is the first extensive study of breast tissue in young women, and the only study to date to show an association of endogenous sex hormones with breast tissue composition in this age group. PUBLIC HEALTH RELEVANCE: We propose to recruit young women, and their mothers, to add to those already examined, to provide a sample large enough for studies of genes associated with variations in breast tissue composition, and to provide data to confirm findings from previous work concerned with hormones and breast tissue composition. The proposed study will examine the relationship between genotype and the phenotypic features of breast tissue. The work completed to date has shown the feasibility of recruiting the number of young women required to achieve these aims. To the best of our knowledge this is the first extensive study of breast tissue in young women, when susceptibility to carcinogenic events is greatest, and variation in breast tissue composition is also greatest. Further, pregnancy, menopause, and other factors associated with ageing have not yet influenced breast tissue composition. For these reasons it may be easier at early ages to detect genetic effects, as well as the effects of environmental exposures unique to early life.

描述(由申请人提供)：这项研究的长期目标是产生可应用于年轻女性预防乳腺癌的新知识。“乳房组织年龄”的派克理论模型和经验流行病学证据表明，乳房在早期特别容易受到致癌物的影响，并表明如果在生命早期就开始预防乳腺癌的策略将是最有效的。以前的工作表明，乳房X光摄影密度(PMD)的变化与中老年女性患乳腺癌的风险差异很大相关，这是高度遗传性的，并且与磁共振(MR)评估的乳房水分含量密切相关。受此启发，我们使用MR检查了年轻女性乳房组织变化的相关因素，到目前为止，我们已经检查了400名年轻女性(年龄在15-30岁)及其母亲。乳房磁共振已经被用来描述所有年轻女性和随机抽样的100名母亲的乳房组织。在15-18岁的年轻女性中，乳房水分的平均水平和变化最大，这一年龄段对致癌物的易感性也最高。我们发现，年轻女性的乳房水分含量与她们的体重和身高相关，这表明生长发育的一般指标与乳房组织的组成有关。与之前描述的遗传影响一致，年轻女性的乳汁含量也与她们母亲的MR和PMD的乳汁含量有关。我们还发现，所有受试者的血液生长激素和性激素结合球蛋白水平与乳房水分含量有关。因此，我们有证据表明，荷尔蒙和遗传因素都会影响年轻女性的乳房组织组成。我们建议在已经检查的基础上再招募年轻女性(15-18岁)，以提供足够大的样本来检查整个基因组的常见遗传变异和乳房组织的表型特征。这个样本还将使我们能够重新检查荷尔蒙和生长因子与这个年龄段的乳房组织组成的关系。迄今完成的工作表明，招募实现这些目标所需数量的年轻妇女是可行的。我们将在绝经前的年轻女性中复制全基因组关联研究的结果，从这些女性中收集DNA和乳房X光照片。据我们所知，这是第一次对年轻女性的乳房组织进行广泛的研究，也是迄今为止唯一一项表明内源性性激素与这个年龄段的乳房组织组成有关的研究。 公共卫生相关性：我们建议招募年轻女性及其母亲，在已经检查的基础上进行补充，提供足够大的样本来研究与乳房组织成分变化相关的基因，并提供数据以证实先前与荷尔蒙和乳房组织组成有关的研究结果。这项拟议的研究将研究基因和乳房组织表型特征之间的关系。迄今完成的工作表明，招募实现这些目标所需数量的年轻妇女是可行的。据我们所知，这是第一次对年轻女性的乳房组织进行广泛研究，年轻女性对致癌事件的易感性最高，乳房组织成分的差异也最大。此外，怀孕、更年期和其他与年龄相关的因素还没有影响乳房组织的组成。由于这些原因，在早期可能更容易发现遗传效应，以及早期生命所特有的环境暴露的影响。