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（由应用提供）：在本应用中，我们提出了几项研究，以实质上提高了我们对脂肪酸的作用，饮食和内源性产生，在乳腺癌发生中的理解。长期以来，已经假设饮食脂肪会增加乳腺癌的风险，但是在大多数大型前瞻性研究中尚未观察到总体关联。尽管饮食脂肪摄入作为暴露的局限在一些研究中已经观察到了绝经前）。生物标志物可能会更亲密地反映饮食脂肪酸的内部剂量，并可以检查内源合成的脂肪酸，这构成了内部暴露于脂肪酸的重要组成部分。我们建议在护士健康研究II（NHSII）的一项嵌套病例对照研究中测量红细胞脂肪酸，这是一群已建立的年轻女性。首先，我们将评估反映乳脂脂肪和肉类摄入的饱和和反式脂肪酸的关联（15：0， 16：1n-7t，18：1n-7t）和来自乳腺癌风险的部分氢化油（18：1和18：2）的反式脂肪酸。我们还将评估与N-3和N-6多不饱和脂肪酸的关联。为了进一步探索可能的机制，我们将研究这些特定脂肪酸与肿瘤组织过表达的炎症标记物的关联。接下来，我们将解决内源合成的脂肪酸的重要组成部分，即9-尿素酶的活性（又称stearoyl-CoA脱发酶1（SCD1）），通过特异性与单不饱和脂肪酸的比率（饱和（SI）N-7和SIN-9）来测量。实验证据表明，SCD1在乳腺肿瘤的生长中很重要，迄今为止，有限的流行病学证据表明，随着SCD1活性的较高，乳腺癌风险增加。我们将进一步研究与脂肪酸合酶（FAS）肿瘤过表达的相关性。我们将利用1996年至1999年从NHSII中的29,611名女性收集的存档（存储在D-130¿C）的血液样本中。我们将使用这些血液样本和归档的肿瘤组织块进行嵌套的病例对照研究，并从大约75％的病例中进行。我们预计乳腺癌有900多例事件，其中包括诊断后的近500名女性绝经前女性和200多名妇女，这些女性在血液中收集血液中，但在诊断后绝经后。我们预计大约有600例患有肿瘤组织的病例。这项研究提供了一个理想的背景，鉴于前瞻性性质，广泛的协变量信息，存档的血液和组织标本以及持续的高速随访率，可以研究这些关联。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，并应为我们对脂肪酸与乳腺癌风险的关联的理解做出重大贡献，这可能导致预防乳腺癌预防以及SCD1和FAS途径的新勘探途径的重要建议。