Circulating fatty acids and breast cancer risk: a prospective study

循环脂肪酸与乳腺癌风险：一项前瞻性研究

基本信息

批准号：
8490526
负责人：
A. Heather Eliassen
金额：
$ 33.64万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8490526
关键词：
Address Animals Archives Area Biological Markers Blood Blood specimen Breast Breast Cancer Prevention Cancer Etiology Cattle Cell membrane Cohort Studies Collection Coronary heart disease Data Diagnosis Diet Dietary Fats Dietary Fatty Acid Dietary intake Disease Association Dose Energy-Generating Resources Enzymes Epidemiology Erythrocyte Membrane Erythrocytes Evaluation Exposure to Fatty Acids Fatty acid glycerol esters Fatty-acid synthase Food Processing Half-Life Human body Intake Interleukin-6 Knowledge Mammary Neoplasms Measures Meat Milk Monounsaturated Fatty Acids Nature Nested Case-Control Study Nurses&apos Health Study Nutrient Oils Oleic Acids Pathway interactions Play Polyunsaturated Fatty Acids Postmenopause Premenopause Production Prospective Studies Recommendation Risk Risk Factors Role Ruminants Sample Size Serum Source Specimen Staining method Stains Stat3 protein Stearoyl-CoA Desaturase Tissues Trans Fats Trans Fatty Acids Tumor Tissue Vegetables Woman aged cancer risk carcinogenesis case control cohort cyclooxygenase 2 desaturase design disease diagnosis follow-up improved in vivo indexing inflammatory marker malignant breast neoplasm modifiable risk palmitoleic acid polyunsaturated fat prospective tumor tumor growth young woman

项目摘要

DESCRIPTION (provided by applicant): In this application we propose several studies to substantially improve our understanding of the role of fatty acids, from both diet and endogenous production, in breast carcinogenesis. Dietary fat has long been hypothesized to increase breast cancer risk, but no overall association has been observed in most large prospective studies. Despite the limitations of dietary fat intake as an exposure, associations with specific types of fat (e.g., animal and trans fats) and/or in specific subsets of women (e.g., premenopausal) have been observed in some studies. Biomarkers are likely to reflect the internal dose of dietary fatty acids more closely and allow for an examination of endogenously synthesized fatty acids, which make up a substantial component of internal exposure to fatty acids. We propose to measure erythrocyte fatty acids in a nested case-control study within the Nurses' Health Study II (NHSII), an established cohort of younger women. First, we will assess the association of saturated and trans fatty acids that reflect intake of dairy fat and meat (15:0, 16:1n- 7t, 18:1n-7t) and trans fatty acids from partially hydrogenated oils (18:1 and 18:2) with breast cancer risk. We also will assess the association with n-3 and n-6 polyunsaturated fatty acids. To further explore possible mechanisms, we will examine the associations of these specific fatty acids with tumor tissue over-expression of inflammatory markers. Next, we will address an important component of endogenously synthesized fatty acids, activity of ¿9-desaturase (a.k.a. stearoyl-CoA desaturase 1 (SCD1)), measured by the ratio of specific saturated to monounsaturated fatty acids, (saturation index (SI)n-7 and SIn-9). Experimental evidence suggests SCD1 is important in breast tumor growth and the limited epidemiologic evidence to date suggests an increased breast cancer risk with higher SCD1 activity. We will further investigate this association with tumor over-expression of fatty acid synthase (FAS). We will utilize archived (stored at d -130¿C) blood samples collected in 1996-1999 from 29,611 women in the NHSII. We will conduct a nested case-control study using these blood samples and archived tumor tissue blocks from approximately 75% of cases. We anticipate more than 900 incident cases of breast cancer, including nearly 500 women premenopausal at diagnosis and more than 200 women who were premenopausal at blood collection but postmenopausal at diagnosis. We expect approximately 600 cases with tumor tissue. This study provides an ideal context in which to investigate these associations, given the prospective nature, extensive covariate information, archived blood and tissue specimens, and an ongoing, high rate of follow-up. Our proposed study will be the first detailed assessment of these associations among premenopausal women and should contribute substantially to our understanding of the associations of fatty acids with breast cancer risk, potentially leading to important recommendations for breast cancer prevention as well as new avenues of exploration in the SCD1 and FAS pathways.

描述（由申请人提供）：在本申请中，我们提出了几项研究，以大幅提高我们对饮食和内源性产生的脂肪酸在乳腺癌发生中的作用的理解。膳食脂肪长期以来一直被用来增加乳腺癌风险。尽管膳食脂肪摄入量作为一种暴露存在局限性，但在大多数大型前瞻性研究中尚未观察到与特定类型脂肪（例如动物脂肪和反式脂肪）和/或特定女性群体（例如女性）之间的关联。在一些研究中已经观察到生物标志物可能更密切地反映膳食脂肪酸的内部剂量，并允许检查内源合成的脂肪酸，它构成了脂肪酸内部暴露的重要组成部分。在护士健康研究 II (NHSII) 的一项巢式病例对照研究中测量红细胞脂肪酸，该研究是一组年轻女性，首先，我们将评估反映乳制品脂肪摄入量和反式脂肪酸的关联。肉 (15:0, 16:1n-7t、18:1n-7t）和部分氢化油中的反式脂肪酸（18:1 和 18:2）与乳腺癌风险的关系我们还将评估与 n-3 和 n-6 的关联。为了进一步探索可能的机制，我们将检查这些特定脂肪酸与肿瘤组织炎症标志物过度表达的关系，接下来，我们将讨论内源合成脂肪酸的重要组成部分，即 ¿ 9-去饱和酶（又称硬脂酰辅酶A去饱和酶 1 (SCD1)），通过特定饱和脂肪酸与单不饱和脂肪酸的比率来测量（饱和指数 (SI)n-7 和 SIn-9），实验证据表明 SCD1 在乳房中很重要。肿瘤生长和迄今为止有限的流行病学证据表明，SCD1 活性越高，乳腺癌风险越高，我们将进一步研究这种与肿瘤脂肪酸合酶过度表达的关系。 (FAS)。我们将利用 1996 年至 1999 年从 NHSII 的 29,611 名女性采集的存档（储存在 -130°C）血液样本。我们将使用这些血液样本和存档的肿瘤组织块进行嵌套病例对照研究。大约 75% 的病例预计将有超过 900 例乳腺癌病例，其中包括近 500 名诊断时处于绝经前的女性和超过 200 名绝经后的女性。考虑到前瞻性性质、广泛的协变量信息、存档的血液和组织标本以及正在进行的研究，我们预计大约有 600 例具有肿瘤组织的绝经前患者。我们提出的研究将是对绝经前妇女中这些关联的首次详细评估，并且应该大大有助于我们了解脂肪酸与乳腺癌风险的关联，并可能为预防乳腺癌提供重要建议。以及 SCD1 和 FAS 途径的新探索途径。