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(诊断为50岁)乳腺癌的病因学很少被了解和研究不足。这些癌症具有更高的侵袭性，激素受体阴性肿瘤的发生率更高，并且与较差的预后有关。在40岁以下的女性中，黑人女性的发病率高于白人女性，但在美国，白人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，更具侵略性，激素受体阴性的肿瘤。最近的证据表明，这可能也适用于社会经济地位较低的女性。与生命过程中能量平衡相关的潜在可改变的危险因素(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。这项研究的目的是在黑人和白人妇女的社会经济多样性人群中，调查生命过程(宫内/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变异是否与乳腺癌总体风险和肿瘤亚型相关。具体目标：在50岁的黑人和白人女性中，我们建议：1)调查成人能量平衡因素--全身(皮下)肥胖、中枢性(内脏)肥胖、血清脂肪因子生物标记物、胰岛素抵抗相关的饮食模式和体力活动--与乳腺癌风险的关系；(2)检查早期生命能量平衡因素--生长、肥胖和月经初潮--与乳腺癌风险的关系；以及(3)研究生命周期能量平衡因素--上述成人和早期生活因素--与乳腺癌风险的联合关系。所有的关联将被研究，(A)种族(黑/白)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)与整个乳腺癌和肿瘤亚型(基底样型、HER2+/雌激素受体(ER)-、Lumina A和Lumina B)的关联。方法：我们建议对2011-2014年间确诊的2000例原位和浸润性乳腺癌病例进行基于人群的病例对照研究，其中黑人(n=1,000)和白人(n=1,000)居住在大都会底特律和洛杉矶县SEER地区，50岁的女性，以及在年龄、种族和SEER地区频率匹配的2000名对照女性的基于人群的样本。我们将收集人体测量、血液、照片、关于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：我们拟议的研究将(1)深入了解年轻女性乳腺癌的潜在可改变的风险因素，(2)检查特定乳腺癌亚型的风险因素，包括侵袭性的基底细胞样/‘三重阴性’肿瘤，(3)成为对年轻非裔美国女性乳腺癌的最大研究，(4)能够调查种族和SES的联合影响，以及(5)为当前和未来的研究创建血液、肿瘤组织微阵列和DNA的生物资料库。

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.