Blood metabolite profiles and risk of developing endometrial cancer

血液代谢特征和患子宫内膜癌的风险

• 批准号: 9982059
• 负责人: Mary Christine Playdon
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-09 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982059
• 关键词: Address; Alcohols; Ancillary Study; Attenuated; Back; Beverages; Big Data; Biological; Biological Markers; Blood; Blood specimen; Body mass index; Breast Cancer Prevention; Cancer Etiology; Cancer Prevention Intervention; Cancer Prevention Study II; Cause of Death; Clinical; Coffee; Colorectal Cancer; Communities; Conflict (Psychology); Consumption; Data; Development; Diagnosis; Diagnostic; Diet; Dietary Assessment; Dietary Factors; Dietary Fats; Dietary Questionnaires; Dietary intake; Disease; Emerging Technologies; Endometrial; Endometrial Carcinoma; Epidemiology; Estrogen receptor negative; Estrogen receptor positive; Etiology; Failure; Fasting; Female; Food; Fruit; Future; Goals; Gold; Hour; Human; Incidence; Individual; Laboratories; Link; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Malignant neoplasm of prostate; Measurement; Measures; Mediation; Meta-Analysis; Metabolic; Metabolic Pathway; Metabolism; Methods; Molecular Epidemiology; Nested Case-Control Study; Nurses' Health Study; Obesity; Outcome; Overweight; Pathway interactions; Patient Self-Report; Phase; Postmenopause; Prospective Studies; Prospective cohort; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Public Health; Questionnaires; Research; Resources; Risk; Risk Factors; Role; Serum; Signal Transduction; Statistical Data Interpretation; Suggestion; Time; Tumor Subtype; United States; Urine; Woman; Women' s Health; Work; base; cancer prevention; cancer risk; cancer subtypes; candidate marker; case control; cohort; diet and cancer; dietary supplements; endometrial cancer prevention; evidence base; feeding; food consumption; improved; insight; interest; malignant breast neoplasm; metabolome; metabolomics; modifiable risk; mortality; new technology; novel; prospective; rare cancer; risk prediction model; standard measure; tool; tumor heterogeneity

PROJECT SUMMARY Cancer is a leading cause of death in the United States, with a third of diagnoses attributed to modifiable risk factors including obesity and poor diet. Understanding the role of these risk factors in cancer development is crucial for the provision of appropriate public health guidance for cancer prevention. Breast cancer remains the highest incidence cancer among women in the United States, and incidence rates for endometrial cancer are projected to dramatically increase over the next decade. Epidemiological, clinical and laboratory evidence suggests that diet may be relevant for breast and endometrial cancer prevention, although the evidence base lacks consistency, perhaps owing to imprecise dietary measures, and a failure to account for associations that may vary by tumor subtype. Furthermore, endometrial cancer is especially obesity-driven, but the underlying mechanisms have yet to be fully characterized. There is a need for better objective measures of diet, including dietary biomarkers, that can be used to improve dietary assessment. Metabolomics is a novel and emerging technology in molecular epidemiology that can be used to measure hundreds to thousands of circulating metabolites simultaneously, more than 200 of which have been recently linked to an individual’s diet and/or adiposity. Furthermore, metabolomics can be used to highlight biological mechanisms of interest in relation to disease. This novel technology is advancing rapidly, and much work is yet to be done in applying it in an epidemiologic context. To address this unmet need, I propose to apply metabolomics to understanding the relationships of diet and adiposity with female cancers. I will first quantify the relationship between circulating metabolites and habitually consumed foods in a feeding study with a gold-standard measure of diet (weighed food) among postmenopausal women in order to develop objective dietary biomarkers. Such work is critical for correct interpretation of any diet-related metabolite signals that may be observed in subsequent cancer studies. Next, I will measure the association between pre-diagnostic circulating diet-related metabolites and estrogen receptor- negative (ER-) breast cancer using nested case-control data from three prospective cohorts. ER- breast cancer is rare, aggressive and understudied. Consequently, the etiology is poorly understood, including potential dietary risk factors. Finally, I will determine whether pre-diagnostic circulating metabolites are associated with incident endometrial cancer, and their relation to diet or adiposity using nested case-control data from four prospective cohorts. No studies have explored metabolite signatures of endometrial cancer and their relation to adiposity and diet using data from US-based prospective studies. These studies may uncover unknown metabolic pathways involved in the etiology of breast and endometrial cancer that may also be applicable to other obesity-driven cancers, and identify key pathways for developing and evaluating targeted cancer prevention interventions.

项目摘要 癌症是美国的主要死亡原因，其中三分之一的诊断归因于可改变的风险 包括肥胖和饮食不佳的因素。了解这些危险因素在癌症发展中的作用是 对于为预防癌症提供适当的公共卫生指导至关重要。 乳腺癌仍然是美国女性中癌症最高的癌症，并且事件发生率 对于子宫内膜癌，预计将在未来十年急剧增加。流行病学，临床 实验室证据表明，饮食可能与乳腺癌和子宫内膜癌的预防有关， 尽管证据基础缺乏一致性，但也许是由于饮食措施而无法进行的 可能因肿瘤亚型而变化的关联。此外，子宫内膜癌尤其是 肥胖驱动的，但潜在的机制尚未充分表征。 需要更好地客观饮食措施，包括饮食生物标志物，可用于改善 饮食评估。代谢组学是一种新颖的分子流行病学技术，可以是 用来简单地测量数百至数千个循环代谢产物，其中200多个 最近与个人的饮食和/或肥胖有关。此外，代谢组学可用于 突出了与疾病有关的生物学机制。这项新技术正在迅速发展， 在流行病学环境中应用它尚未完成许多工作。 为了满足这种未满足的需求，我建议应用代谢组学来了解饮食的关系和 女性癌症的肥胖性。我将首先量化循环代谢产物与习惯的关系 在一项喂食研究中，食用食物，并通过金标准的饮食测量（称重食物） 绝经后妇女为了发展客观的饮食生物标志物。这样的工作对于正确至关重要 对随后的癌症研究中可能观察到的任何与饮食相关的代谢物信号的解释。接下来，我 将测量诊断前循环饮食相关的代谢产物与雌激素受体之间的关联 使用来自三个前瞻性队列的嵌套病例对照数据阴性（ER-）乳腺癌。 ER-乳腺癌 是罕见，侵略性和理解的。因此，病因学得不到理解，包括潜力 饮食危险因素。最后，我将确定诊断前循环代谢物是否与 事件的子宫内膜癌及其与四个嵌套的病例对照数据与饮食或肥胖的关系 潜在队列。没有研究探讨了子宫内膜癌的代谢产物及其与 使用来自美国前瞻性研究的数据的肥胖和饮食。这些研究可能会发现未知的 参与乳腺癌和子宫内膜癌病因的代谢途径也可​​能适用于 其他肥胖驱动的癌症，并确定开发和评估靶向癌症的关键途径 预防干预措施。

项目成果

Measuring Dietary Botanical Diversity as a Proxy for Phytochemical Exposure.

• DOI: 10.3390/nu13041295
• 发表时间: 2021-04-14
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Thompson HJ;Levitt JO;McGinley JN;Chandler P;Guenther PM;Huybrechts I;Playdon MC
• 通讯作者: Playdon MC