Plasma Lipid Markers and Cancer Risk

血浆脂质标志物和癌症风险

• 批准号: 8548295
• 负责人: Lu Wang
• 金额: $ 8.29万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-20 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8548295
• 关键词: Address; Affect; Alcohol consumption; American; Anti-Inflammatory Agents; Anti-inflammatory; Apolipoprotein A-I; Apolipoproteins; Biological Markers; Blood; Blood specimen; Body mass index; Cardiovascular Diseases; Cause of Death; Characteristics; Chemoprevention; Cholesterol; Cohort Analysis; Cohort Studies; Collection; Colorectal Cancer; Data; Disease; Documentation; Effectiveness; Endometrial Carcinoma; Environment; Estrogen Receptor Status; Evaluation; Goals; Gonadal Steroid Hormones; Health; High Density Lipoprotein Cholesterol; High Risk Woman; High-Risk Cancer; Hormone Receptor; Hormones; Individual; Inflammation; Insulin Resistance; LDL Cholesterol Lipoproteins; Lipids; Malignant Neoplasms; Measures; Menopausal Status; Metabolic syndrome; Monitor; Obesity; Oxidative Stress; Participant; Pharmaceutical Preparations; Physical activity; Plasma; Postmenopause; Prospective Studies; Proteins; Public Health; Research Design; Risk; Risk Marker; Role; Sample Size; Testing; Triglycerides; Woman; Women' s Health; base; blood lipid; cancer chemoprevention; cancer prevention; cancer risk; cardiovascular disorder risk; cohort; cost; design; follow-up; innovation; malignant breast neoplasm; novel; pre-clinical; prevent; prospective; public health relevance; screening; tumor

DESCRIPTION (provided by applicant): In this application, we will take advantage of the existing data of plasma lipid markers in 28,345 Women's Health Study (WHS) participants and conduct a detailed, prospective cohort evaluation of standard lipid markers (total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, triglycerides), and novel lipid markers (apolipoprotein A-1 (Apo A-1) and Apo B100), as well as long-term use of statins in relation to risk of total invasive cancer and breast, colorectal and endometrial cancer. Blood lipids may affect cancer risk through their association with insulin resistance, inflammation and oxidative stress. Statins have anti- inflammatory, proapoptotic, and antiproliferative effects, which may make them relevant to cancer prevention. Also, we will evaluate these associations by factors that affect plasma lipid levels (e.g., menopausal status, body mass index, physical activity, postmenopausal hormone use, alcohol intake, and other plasma obesity- related markers), as well as by tumor characteristics (e.g., estrogen receptor status). We will also address the issue that the preclinical disease may alter blood lipid levels by conducting an analysis of excluding the first 2 years of follow-up. By June 2011, with a mean follow-up duration of 17 years, we expect 3,506 confirmed incident invasive cancers, including 1,473 breast cancers, 338 colorectal cancers, and 304 endometrial cancers in 28,345 women who provided a baseline blood sample and were free of cancer and cardiovascular disease at baseline. Standard and novel lipid markers were already measured in these 28,345 blood samples. Thus, this proposed study affords a unique and extraordinary opportunity to conduct a prospective cohort analysis of plasma lipid markers and cancer risk. This proposed study is innovative as the associations between plasma Apo A-1 and Apo B100 and cancer risk are largely unexplored in prospective studies. Few studies have examined blood lipid markers and long-term statin use in relation to endometrial cancer risk. This proposed study will be the first evaluation of the relations between plasma Apo A-1 and Apo B100 and overall cancer risk and between Apo B100 and endometrial cancer risk, as well as the first prospective evaluation of Apo A-I and risk of breast and endometrial cancer. This study also has numerous other strengths, including the prospective cohort study design, large sample size (n = 28,345), large numbers of cases (n = 3,506), long duration of follow-up (17 years), excellent environment, availability of other plasma obesity-related markers, detailed information on covariates and tumor characteristics. The ongoing WHS provides follow-up, ascertainment and documentation of cancer cases, and data on biomarkers, statin use, and covariates. Thus, this proposed study affords a unique opportunity to test promising hypotheses about cancer risk in an exceptionally cost-efficient manner. Findings from this study will help clarify the role of plasma lipid markers in identifying women at high risk of cancer who would most benefit from chemoprevention or increased screening and the role of long-term use of statins in cancer chemoprevention.

描述（申请人提供）：在本申请中，我们将利用28，345名女性健康研究（WHS）参与者的血脂标志物的现有数据，并对标准血脂标志物进行详细的前瞻性队列评估（总胆固醇、低密度脂蛋白胆固醇（LDL-C）、HDL-C、甘油三酯），和新的脂质标志物（载脂蛋白A-1（Apo A-1）和Apo B100），以及长期使用他汀类药物与总浸润性癌和乳腺癌、结直肠癌和子宫内膜癌的风险有关。血脂可能通过与胰岛素抵抗、炎症和氧化应激的关系影响癌症风险。他汀类药物具有抗炎、促凋亡和抗增殖作用，这可能使其与癌症预防相关.此外，我们将通过影响血脂水平的因素（例如，绝经状态、体重指数、体力活动、绝经后激素使用、酒精摄入和其它血浆肥胖相关标记），以及肿瘤特征（例如，雌激素受体状态）。我们还将通过排除前2年随访的分析来解决临床前疾病可能改变血脂水平的问题。到2011年6月，平均随访时间为17年，我们预计在28，345名提供基线血液样本且基线时无癌症和心血管疾病的女性中有3，506例确诊的侵袭性癌症，包括1，473例乳腺癌，338例结直肠癌和304例子宫内膜癌。在这28，345份血液样本中已经测量了标准和新型脂质标志物。因此，这项拟议的研究提供了一个独特的和非凡的机会，进行前瞻性队列分析血脂标志物和癌症的风险。这项拟议的研究是创新的，因为血浆Apo A-1和Apo B100与癌症风险之间的关联在前瞻性研究中基本上未被探索。很少有研究检查血脂标志物和长期使用他汀类药物与子宫内膜癌风险的关系。这项拟议的研究将是第一次评估血浆Apo A-1和Apo B100与总体癌症风险之间的关系，以及Apo B100与子宫内膜癌风险之间的关系，也是第一次对Apo A-I与乳腺癌和子宫内膜癌风险进行前瞻性评估。本研究还具有许多其他优势，包括前瞻性队列研究设计、大样本量（n = 28，345）、大量病例（n = 3，506）、长期随访（17年）、良好的环境、其他血浆肥胖相关标志物的可用性、协变量和肿瘤特征的详细信息。正在进行的WHS提供癌症病例的随访、确认和记录，以及生物标志物、他汀类药物使用和协变量的数据。因此，这项拟议的研究提供了一个独特的机会，以非常具有成本效益的方式测试有关癌症风险的有希望的假设。这项研究的结果将有助于澄清血脂标志物在识别女性中的作用， 癌症高危人群最能从化学预防或增加筛查中获益，以及长期使用他汀类药物在癌症化学预防中的作用。