Central Obesity in Relation to Breast Cancer Risk and Survival

中心性肥胖与乳腺癌风险和生存的关系

• 批准号: 9918268
• 负责人: Serena Catherine Houghton
• 金额: $ 6.93万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-25 至 2021-07-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9918268
• 关键词: Address; Androgen Receptor; Androgens; Biological; Body mass index; Breast Cancer Prevention; Breast Cancer Risk Factor; Breast Carcinogenesis; Cancer Prognosis; Central obesity; Characteristics; Chemoprevention; Data; Development; Diagnosis; Estrogen Receptor Status; Estrogen Receptors; Estrogens; Etiology; High Risk Woman; Hip region structure; Hormonal; Hormones; Inflammatory; Insulin; Insulin Receptor; Lead; Link; Mammary Neoplasms; Measurement; Measures; Medical Records; Menopausal Status; Metabolic; Morbidity - disease rate; Mutation; Nurses' Health Study; Obesity; PIK3CA gene; PTEN gene; Pathway interactions; Pharmaceutical Preparations; Physical activity; Postmenopause; Premenopause; Progesterone; Prospective cohort; Questionnaires; Reporting; Research; Resources; Risk; Risk Factors; Risk Reduction; Role; Sample Size; Subgroup; Time; Tumor Markers; Tumor Tissue; Visceral fat; Waist-Hip Ratio; Woman; Work; adipokines; breast cancer diagnosis; breast cancer survival; burden of illness; cancer survival; carcinogenesis; cytokine; epidemiology study; follow-up; high risk; improved; insight; insulin signaling; malignant breast neoplasm; modifiable risk; molecular marker; molecular subtypes; mortality; receptor expression; risk prediction model; screening; tumor; waist circumference

PROJECT SUMMARY/ ABSTRACT Given the substantial morbidity and mortality associated with a diagnosis of breast cancer, the identification of modifiable risk factors and women at high risk for breast cancer is imperative. Body mass index (BMI), a general measure of overall adiposity, is a risk factor that has been well established to be inversely related to premenopausal breast cancer and positively associated with postmenopausal breast cancer. In contrast, central adiposity, measured by waist circumference (WC) or waist-to-hip ratio (WHR), is characterized by high levels of metabolically active visceral fat that leads to alterations in multiple hormones (e.g., insulin), inflammatory cytokines, and adipokines, all of which have been implicated in breast cancer development. Thus, I hypothesize that measures of central adiposity provide further information about breast cancer risk and survival in addition to BMI. To date, few studies have had the statistical power to evaluate the link with premenopausal breast cancers and even fewer have evaluated associations according to important tumor characteristics and molecular subtypes. Therefore, I propose to improve understanding of the role of central adiposity in breast cancer risk and survival. I aim to: 1) examine the independent association of central adiposity with breast cancer risk by menopausal status and determine whether significant predictive information is gained by adding central adiposity to the validated Rosner-Colditz risk prediction model; 2) examine the relationship by tumor molecular subtypes; 3) examine the relationship by several key tumor characteristics (i.e., estrogen receptor, androgen receptor, insulin receptor expression, PTEN loss, PIK3CA mutations); and 4) lastly examine the association between central obesity and breast cancer survival. To address these aims, I will utilize the rich questionnaire and biospecimen resources from two large prospective cohorts, the Nurses' Health Study and Nurses' Health Study II. The women reported waist and hip circumferences at two time points and breast cancer that was confirmed via medical record review. Additionally, I have information on several tumor characteristics measured from available breast tumor tissue blocks. With a large number of premenopausal breast cancer cases, multiple waist measurements, long follow- up, and detailed tumor data, I will improve understanding of central obesity's role in breast carcinogenesis. By evaluating subtypes and tumor characteristics, I should gain substantial new insight into biological mechanisms and help confirm causality. This will allow us to identify women at higher risk for breast cancer development and lower risk of breast cancer survival. Secondly, results gained from this work may improve risk prediction models to help identify women at high risk of developing breast cancer who would be potential candidates for potential chemoprevention or other risk-reducing options (e.g., increasing physical activity).

项目摘要/摘要 鉴于与乳腺癌诊断相关的相当高的发病率和死亡率，确定 可改变的危险因素和患乳腺癌的高危妇女势在必行。体重指数(BMI) 全面肥胖的一般衡量标准，是一个已被充分证实的风险因素，它与 绝经前乳腺癌与绝经后乳腺癌呈正相关。相比之下， 中心性肥胖，通过腰围(WC)或腰臀比(WHR)来衡量，其特征是高 代谢活跃的内脏脂肪水平会导致多种激素(如胰岛素)的变化， 炎性细胞因子和脂肪因子，所有这些都与乳腺癌的发生有关。 因此，我假设中心性肥胖的测量提供了关于乳腺癌风险和 生存除了体重指数。到目前为止，很少有研究有统计能力来评估与 绝经前乳腺癌和更少的人根据重要的肿瘤评估了相关性 特征和分子亚型。因此，我建议提高对中央的作用的理解 肥胖与乳腺癌的风险和存活率。我的目标是：1)考察中央银行的独立协会 肥胖与绝经状态对乳腺癌风险的预测是否有显著意义 信息是通过将中心性肥胖添加到经过验证的Rosner-Colditz风险预测模型中获得的；2) 通过肿瘤分子亚型来检验它们之间的关系；3)通过几种关键肿瘤来检验它们之间的关系 特征(即雌激素受体、雄激素受体、胰岛素受体表达、PTEN缺失、PIK3CA 突变)；以及4)最后研究中心性肥胖与乳腺癌存活率之间的关系。至 为了达到这些目标，我将从两个大的角度利用丰富的调查问卷和生物样品资源 队列，护士健康研究和护士健康研究II。女性报告腰部和臀部 两个时间点的周长和通过病历审查确认的乳腺癌。 此外，我还有从现有的乳腺肿瘤组织中测量到的几个肿瘤特征的信息。 街区。绝经前乳腺癌病例多，腰围多，随访时间长- 上，详细的肿瘤数据，我将加深对中心性肥胖在乳腺癌发生中的作用的理解。通过 评估亚型和肿瘤特征，我应该对生物学机制有实质性的新见解 并帮助确认因果关系。这将使我们能够确定患乳腺癌风险较高的女性。 更低的乳腺癌存活率。其次，这项工作的结果可能会改善风险预测 帮助识别可能患乳腺癌的高危女性的模特 潜在的化学预防或其他降低风险的选择(例如，增加体力活动)。