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发病率，更具侵袭性，激素受体阴性肿瘤，与较差的预后相关。40岁以下女性的发病率在黑人女性中高于白人女性，但在美国，白人女性的风险似乎在增加。年轻黑人女性患侵袭性更强、激素受体阴性肿瘤的几率也更高。最近的证据表明，社会经济地位较低的女性可能也是如此。与生命过程中能量平衡相关的潜在可改变的风险因素（如生长模式、青春期成熟、肥胖、胰岛素抵抗、饮食和身体活动）与年轻女性乳腺癌的病因有关。本研究的目的是在不同社会经济背景的黑人和白人女性人群中，调查生命过程（子宫/围产期、儿童、青少年和成人）能量平衡因素或能量平衡途径候选基因的多态性变异是否与乳腺癌总体风险和肿瘤亚型相关。具体目的：在50岁以下的黑人和白人女性中，我们提出：1)调查成人能量平衡因子-全身（皮下）肥胖，中枢（内脏）肥胖，血清脂肪因子生物标志物，胰岛素抵抗相关饮食模式和身体活动-与乳腺癌风险之间的关系；(2)研究生命早期能量平衡因子——生长、肥胖和月经开始——与乳腺癌风险之间的关系；(3)研究生命过程中能量平衡因素（上述成年和早期生活因素）与乳腺癌风险之间的联合关系。所有的关联都将被研究，(a)根据种族（黑/白）和SES， (b)结合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、HER2+/雌激素受体(ER)-、Luminal a和Luminal b）。方法：我们拟开展一项基于人群的病例对照研究，研究对象为2011年至2014年间诊断出的2000例原位和浸润性乳腺癌病例，分别为居住在底特律大都会区和洛杉矶县SEER区年龄< 50岁的黑人（n= 1000）和白人（n= 1000）女性，以及2000名年龄、种族和SEER区频率匹配的对照女性。我们将收集人体测量数据、血液、照片、生命过程能量平衡和其他已知危险因素的问卷数据以及肿瘤组织。意义:我们提出的研究将：(1)为年轻女性乳腺癌的潜在可改变的危险因素提供见解，(2)检查特定乳腺癌亚型的危险因素，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，(5)为当前和未来的研究创建血液，肿瘤组织微阵列和DNA的生物储库。

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.