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（由申请人提供）：在本申请中，我们将利用28,345名女性健康研究（WHS）参与者的现有数据数据，并进行标准脂质标记的详细，前瞻性同队评估（总胆固醇，总脂蛋白胆固醇，低密度脂蛋白胆固醇（LDL-C），HDLIPIN，TRIGLIPINS，TRIGLIPIND和TRIGINS，TRIGLIPIND和HAPILIN）（ A-1（APO A-1）和APO B100），以及他汀类药物在整体侵入性癌症和乳腺癌，结直肠癌和子宫内膜癌中的长期使用。血脂可能会通过与胰岛素抵抗，炎症和氧化应激的关联来影响癌症的风险。他汀类药物具有抗炎，促凋亡和抗增殖作用，这可能使它们与预防癌症有关。此外，我们将通过影响血浆脂质水平的因素（例如，绝经状态，体重指数，体育活动，绝经后激素使用，酒精摄入量和其他血浆肥胖相关标记）以及肿瘤特征（例如，雌激素受体状态）。我们还将解决临床前疾病可能通过不包括随访的前两年的分析来改变血脂水平的问题。到2011年6月，我们预计3,506例确认的入侵癌症的平均随访时间为17年，其中包括1,473家乳腺癌，338种结直肠癌和304个子宫内膜癌，其中28,345名提供了基线血液样本，并在基线的癌症和心血管疾病中免费。在这28,345种血液样本中已经测量了标准和新型脂质标记。因此，这项拟议的研究为进行血浆脂质标记和癌症风险的前瞻性队列分析提供了一个独特而非凡的机会。这项拟议的研究具有创新性，因为在前瞻性研究中，血浆APO A-1和APO B100与癌症风险之间的关联在很大程度上尚未探索。很少有研究检查了血脂标记和与子宫内膜癌风险有关的长期他汀类药物的使用。这项拟议的研究将是对等离子体APO A-1和APO B100与总体癌症风险以及APO B100和子宫内膜癌风险之间的关系的首次评估，以及对APO A-I以及乳腺癌和子宫内膜癌的风险的首次预期评估。这项研究还具有许多其他优势，包括前瞻性队列研究设计，大型样本量（n = 28,345），大量病例（n = 3,506），长时间的随访时间（17年），良好的环境，其他等离子体肥胖相关的标记的可用性，有关协会和肿瘤特征的详细信息。正在进行的WHS提供了癌症病例的随访，确定和记录，以及有关生物标志物，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，以异常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阐明血浆脂质标记在识别女性处的作用 癌症的高风险将受益于化学预防或增加筛查以及他汀类药物在癌症化学预防中的长期作用。