Interactions of Coenzyme Q10 with plasma tocopherols and their role in breast can

辅酶 Q10 与血浆生育酚的相互作用及其对乳腺的作用

• 批准号: 7500751
• 负责人: ROBERT COONEY
• 金额: $ 6.17万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-25 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7500751
• 关键词: ATP Synthesis Pathway; Age; Aging; Analytical Chemistry; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Attention; Basic Science; Biometry; Blood; Breast; C-reactive protein; Cancer Etiology; Cells; Cessation of life; Clinical Research; Coenzyme Q10; Cohort Studies; DNA Damage; Data; Dependence; Development; Dietary Fats; Disease; Electron Transport; Elements; Epidemiologic Studies; Epidemiology; Ethnic group; Etiology; Exhibits; Generations; Grant; Health; Human; In Vitro; Incidence; Individual; Inflammation; Intake; Lipids; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Mediating; Mitochondria; Neoplastic Cell Transformation; Nitric Oxide; Nitrogen; Nitrogen Oxides; Normal Cell; Numbers; Oxidants; Oxygen; Phase; Physiological; Physiology; Plasma; Play; Process; Prospective Studies; Range; Reactive Oxygen Species; Regulation; Reporting; Risk; Risk Marker; Role; Sampling; Serum; System; Tissues; Tocopherols; Woman; alpha Tocopherol; cancer risk; cancer type; carcinogenesis; cell type; cohort; cost; gamma-Tocopherol; immune function; in vivo; innovation; insight; male; malignant breast neoplasm; men; mitochondrial dysfunction; mortality; novel; oxidation; prevent; prospective; response; small molecule; tumor

DESCRIPTION (provided by applicant): Coenzyme Q10 is of critical importance to mitochondrial function and its deficiency is associated with impaired ATP synthesis, apoptosis, and immune function. Its decease in tissue levels with age is associated with mitochondrial dysfunction and aging. There have been no major epidemiologic studies exploring the relationship between Coenzyme Q10 and breast cancer incidence and all cause mortality. Indeed, prospective studies relating this major endogenous lipid-phase anti-oxidant and key element of the electron transport chain to any type of cancer are nonexistent. Intriguing small clinical studies have suggested a possible beneficial effect of Coenzyme Q10, however supportive epidemiologic data is not available. There is compelling evidence that Coenzyme Q10 may play an important general role in the development and progression of many tumor types and preliminary evidence for an association with prostate cancer incidence and all- cause mortality in men is presented. It is proposed to utilize stored extracts from 2,193 women (731 incident cases of breast cancer and 1,462 matched controls) from two large prospective cohorts to determine the association of plasma coenzyme Q10 with breast cancer risk and all-cause mortality. In addition we observe intriguing relationships between Coenzyme Q10 and plasma levels of alpha and gamma-tocopherols, as well as C-Reactive Protein that may have a significant impact on the interpretation of the role of these dietary lipid-phase antioxidants on cancer development and progression in general. Analysis of Coenzyme Q10 in tandem with the individual tocopherols should provide significant new insight into the possible role of these essential lipids in the etiology of breast cancer and aging, as well as the interpretation of the meaning of plasma levels of these molecules. We hypothesize that an optimal level of Coenzyme Q10 will be determined that is associated with reduced risk for breast cancer and all- cause mortality. The project will explore the relation between coenzyme Q10, alpha-tocopherol, and gamma-tocopherol with breast cancer incidence and all-cause mortality in women utilizing previously collected samples from 2,193 women. It will greatly benefit our understanding of the association of these essential lipids with breast cancer and help to elucidate the potential role of plasma coenzyme Q10 in human physiology.

描述（由申请人提供）：辅酶Q10对于线粒体功能至关重要，其缺乏与ATP合成，凋亡和免疫功能受损有关。它随着年龄的增长而在组织水平上的脱发与线粒体功能障碍和衰老有关。没有主要的流行病学研究来探讨辅酶Q10与乳腺癌发生率的关系以及所有导致死亡率。实际上，将这种主要的内源性脂质相抗氧化剂和电子传输链与任何类型的癌症的关键要素有关的前瞻性研究不存在。有趣的小型临床研究表明，辅酶Q10可能具有有益作用，但是尚无支持的流行病学数据。有令人信服的证据表明，辅酶Q10可能在许多肿瘤类型的发展和发展中起重要作用，以及与前列腺癌发病率和全部导致男性死亡率相关的初步证据。提议利用来自两个大型前瞻性队列的2,193名女性（731例乳腺癌事件和1,462例匹配对照）中的储存提取物来确定血浆辅助Q10与乳腺癌风险和全因死亡率的关联。此外，我们观察到辅酶Q10与α和γ-生育酚的血浆水平之间的有趣关系，以及C反应性蛋白，这可能对这些饮食中脂质相抗氧化剂在癌症发展和进展的饮食中脂质相抗氧化剂的作用的解释可能产生重大影响。与单个生育酚在串联中的辅酶Q10分析应为这些基本脂质在乳腺癌和衰老的病因学中的可能作用以及对这些分子等离子体水平的含义的解释提供重大新的见解。我们假设将确定最佳水平的辅酶Q10，这与乳腺癌的风险降低和所有导致死亡率有关。该项目将探索辅酶Q10，α-生育酚和γ-生育酚与乳腺癌发病率的γ-生育酚与使用2193名妇女的先前收集样品的女性中的乳腺癌发病率和全因死亡率之间的关系。这将极大地有利于我们对这些基本脂质与乳腺癌的关联的理解，并有助于阐明血浆辅酶Q10在人类生理学中的潜在作用。