The obesity-metabolic biomarker axis and breast cancer risk

现有的流行病学研究表明，肥胖和乳腺癌之间存在复杂的关系， 肥胖通常与绝经后妇女风险增加有关，但在绝经后妇女中 绝经前的女性。关于黑人女性肥胖-乳腺癌协会的信息有限， 肥胖率最高的人群，三重负(和基底样)乳房的发生率更高 癌症)，但腔内亚型的发病率较低。可能存在不一致的关联 黑人和白人患肥胖症和乳腺癌的风险是由他们潜在的 肥胖与乳腺癌风险相关的机制。尽管这些机制不是 很明显，人们普遍认为肥胖主要是通过诱导胰岛素信号和抵抗来起作用的， 增加雌激素的生物合成和炎症会增加患乳腺癌的风险。相对的 这些机制对乳腺癌发病机制的贡献在黑人和白人之间可能有所不同， 这可能是导致亚型乳腺癌风险的种族差异的原因之一。我们在此提出一个案例-- 南方社区队列中嵌套绝经后乳腺癌的对照研究 这项研究追踪了50,000多名女性的乳腺癌和其他癌症，其中三分之二是黑人 发病率。这一队列是从肥胖普遍存在的低收入人群中招募的(58%的SCC 黑人女性的体重指数为30公斤/米。具体目标是： 目的1.测定循环中IGF1、IGF结合蛋白3、脂联素、瘦素、C反应蛋白和 性激素[雌二醇、雌酮、睾酮和性激素结合球蛋白(SHBG)]与 绝经后乳腺癌的风险，以及它们是否因种族和/或肿瘤雌激素/孕激素而不同 接收器状态。 目的2.确定肥胖状态是否上调肿瘤IGF1信号，雌激素受体(ER) 信号和炎症基因表达特征增加乳腺癌风险，如果 上调因种族而异 目的3.确定诊断前IGF1、性激素和炎症的循环水平 标记与IGF1信号、ER信号和炎症基因表达信号有关， 分别在乳腺癌组织中

Existing epidemiologic studies suggest a complex relationship between obesity and breast cancer, with obesity generally associated with increased risk among postmenopausal women but reduced risk among premenopausal women. Limited information exists on the obesity-breast cancer association for black women, the group with the highest prevalence of obesity, higher incidence of triple negative (and basal-like) breast cancer), but lower incidence of the luminal subtype. It is possible that inconsistent associations between obesity and breast cancer risk in blacks and whites are explained by their differences in underlying mechanisms through which obesity is related to breast cancer risk. Although these mechanisms are not entirely clear, it is in general believed that obesity acts primarily by inducing insulin signaling and resistance, increased estrogen biosynthesis and inflammation to increase the risk of breast cancer. The relative contribution of these mechanisms to the pathogenesis of breast cancer may differ between blacks and whites, which may contribute to racial difference in risk of breast cancer by subtype. We propose herein a case- control study of postmenopausal breast cancer nested within the prospective Southern Community Cohort Study that is tracking over 50,000 women, two-thirds of whom are black, for breast and other cancer incidence. This cohort was recruited from a low-income population where obesity is common (58% of SCCS black women have a BMI>30 kg/m^. Specific aims are: Aim 1. To determine whether circulating levels of IGF1, IGF-binding protein 3, adiponectin, leptin, CRP and sex hormones [estradiol, estrone, testosterone and sex hormone-binding globulin (SHBG)] are associated with risk of postmenopausal breast cancer, and whether they differ by race and/or tumor estrogen/progesterone receptor status. Aim 2. To determine whether the obese state upregulates tumor IGF1 signaling, estrogen receptor (ER) signaling and inflammation gene expression signatures to increase breast cancer risk, and if the extent of upregulation differs by race Aim 3. To determine whether pre-diagnostic circulating levels of IGF1, sex hormones and inflammation markers are associated with IGF1 signaling, ER signaling and inflammation gene expression signatures, respectively, in breast cancer tissues