Life Course Energy Balance and Breast Cancer Risk in Black/White Women Under 50

描述（由申请人提供）：年轻女性（诊断年龄< 50岁）乳腺癌的病因学知之甚少，研究不足。这些癌症具有更高的侵袭性、激素受体阴性肿瘤的患病率，并且与较差的预后相关。黑人女性40岁以下的发病率高于白色女性，但美国白色女性的风险似乎正在增加。年轻的黑人女性也有更高的发病率更积极的，激素受体阴性肿瘤。最近的证据表明，这可能也适用于社会经济地位较低的妇女。与生命过程中的能量平衡有关的潜在可改变的风险因素（例如生长模式、青春期成熟、肥胖、胰岛素抵抗、饮食和体力活动）与年轻女性乳腺癌的病因有关。本研究的目的是调查，在一个社会经济多样化的黑人和白色妇女的人口，是否生命过程（在子宫内/围产期，儿童，青少年和成人）能量平衡因素，或多态性变异的候选基因的能量平衡途径，与乳腺癌的风险整体和肿瘤亚型。具体目标：在< 50岁的黑人和白色女性中，我们提出：1）调查成人能量平衡因子之间的关联-一般（皮下）肥胖，中枢性（内脏）肥胖，血清脂肪因子生物标志物，胰岛素抵抗相关的饮食模式，和体力活动-与乳腺癌的风险;（2）研究生命早期能量平衡因素--生长、肥胖和月经开始--与乳腺癌风险之间的关系;（3）研究生命过程能量平衡因子（上述成人和早期生命因子）与乳腺癌风险之间的联合关系。将研究所有相关性，（a）按人种（黑人/白色）和SES，（B）与能量平衡途径中的候选基因（基于功能和全基因组关联研究），以及（c）总体乳腺癌和肿瘤亚型（基底样、HER 2 +/雌激素受体（ER）-、管腔A和管腔B）。研究方法：我们建议对2011年至2014年诊断的2,000例原位和浸润性乳腺癌病例进行一项基于人群的病例对照研究，这些病例来自居住在底特律大都会和洛杉矶县SEER地区的50岁以下黑人（n= 1,000）和白色（n=1,000）女性，以及2,000例年龄频率匹配的对照女性的基于人群的样本，种族和SEER地区。我们将收集人体测量数据、血液、照片、关于生命过程能量平衡和其他已知风险因素的问卷调查数据以及肿瘤组织。重要性：我们提出的研究将，（1）提供对年轻女性乳腺癌潜在可改变的风险因素的见解，（2）检查特定乳腺肿瘤亚型的风险因素，包括侵袭性基底样/“三阴性”肿瘤，（3）是年轻非洲裔美国女性乳腺癌的最大研究，（4）有能力调查种族和SES的联合影响，以及（5）创建血液、肿瘤组织微阵列和DNA的生物储存库，用于当前和未来的研究。

DESCRIPTION (provided by applicant): The etiology of breast cancer in younger women (diagnosed < 50 years of age) is poorly understood and understudied. These cancers have a higher prevalence of more aggressive, hormone receptor negative tumors and are associated with poorer prognosis. The incidence rate among women through age 40 years is higher among Black vs. White women, but risk appears to be increasing among White women in the United States. Young Black women also have a higher prevalence of more aggressive, hormone receptor negative tumors. Recent evidence suggests this may also be true for women of lower socioeconomic status (SES). Potentially modifiable risk factors related to energy balance over the life course (e.g. growth patterns, pubertal maturation, adiposity, insulin resistance, diet and physical activity) have been implicated in the etiology of breast cancer in younger women. The objectives of this study are to investigate, in a socioeconomically diverse population of Black and White women, whether life course (in utero/perinatal, childhood, adolescent, and adult) energy balance factors, or polymorphic variation in candidate genes in energy balance pathways, are associated with breast cancer risk overall and by tumor subtype. Specific Aims: Among Black and White women < 50 years, we propose: 1) To investigate the association between adult energy balance factors-general (subcutaneous) adiposity, central (visceral) adiposity, serum adipokine biomarkers, an insulin resistance related diet pattern, and physical activity-with breast cancer risk; (2) To examine the association between early life energy balance factors-growth, adiposity, and onset of menses-with breast cancer risk; and (3) To study joint associations between life course energy balance factors-aforementioned adult and early life factors-with breast cancer risk. All associations will be studied, (a) by race (Black/White) and SES, (b) jointly with candidate genes in the energy balance pathway (based on function and genome wide association studies), and (c) for overall breast cancer and by tumor subtype (basal-like, HER2+/estrogen receptor (ER)-, Luminal A, and Luminal B). Methods: We propose to conduct a population-based case control study of 2,000 incident in situ and invasive breast cancer cases, diagnosed from 2011 to 2014, in Black (n=1,000) and White (n=1,000) women aged < 50 years residing in Metropolitan Detroit and Los Angeles County SEER areas, and a population-based sample of 2,000 control women frequency-matched on age, race and SEER area. We will collect anthropometric measurements, blood, photographs, questionnaire data on life course energy balance and other known risk factors, and tumor tissue. Significance: Our proposed study will, (1) provide insight into potentially modifiable risk factors for breast cancer in younger women, (2) examine risk factors for specific breast tumor subtypes, including the aggressive basal-like/'triple negative' tumors, (3) be the largest study of breast cancer in younger African American women, (4) have the ability to investigate the joint effect of race and SES, and (5) create a bio-repository of blood, tumor tissue microarrays and DNA for current and future study.