Plasma Lipid Markers and Cancer Risk

描述（由申请人提供）：在本应用中，我们将利用28345名妇女健康研究（WHS）参与者的现有血浆脂质标志物数据，对标准脂质标志物（总胆固醇、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白c、甘油三酯）、新型脂质标志物（载脂蛋白a -1 （Apo a -1）和载脂蛋白B100）以及长期使用他汀类药物与浸润性癌症和乳腺癌风险的关系进行详细的前瞻性队列评估。结直肠癌和子宫内膜癌。血脂可能与胰岛素抵抗、炎症和氧化应激有关，从而影响癌症风险。他汀类药物具有抗炎、促细胞凋亡和抗细胞增殖的作用，这可能使其与癌症预防有关。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、酒精摄入量和其他血浆肥胖相关标志物）以及肿瘤特征（例如，雌激素受体状态）来评估这些关联。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，其中28,345名妇女提供了基线血液样本，基线时无癌症和心血管疾病。在这28,345份血液样本中已经测量了标准的和新型的脂质标记物。因此，这项提出的研究提供了一个独特而非凡的机会来进行血浆脂质标志物和癌症风险的前瞻性队列分析。这项研究具有创新性，因为血浆载脂蛋白A-1和载脂蛋白B100与癌症风险之间的关系在前瞻性研究中很大程度上未被探索。很少有研究检查血脂指标和长期使用他汀类药物与子宫内膜癌风险的关系。本研究将首次评价血浆Apo A-1和Apo B100与总体癌症风险、Apo B100与子宫内膜癌风险之间的关系，以及Apo A-I与乳腺癌和子宫内膜癌风险的首次前瞻性评价。本研究还有许多其他优势，包括前瞻性队列研究设计，样本量大（n = 28,345），病例数多（n = 3,506），随访时间长（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提供了癌症病例的随访、确定和记录，以及生物标志物、他汀类药物使用和协变量的数据。因此，这项提议的研究提供了一个独特的机会，以一种非常经济有效的方式来测试有关癌症风险的有希望的假设。本研究的结果将有助于阐明血浆脂质标志物在鉴别女性糖尿病中的作用

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. PUBLIC HEALTH RELEVANCE: The proposed study will conduct a comprehensive, prospective cohort evaluation of standard lipid markers of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, and novel lipid markers of apolipoproteins A-1 and B100 , as well as long-term use of statins in relation to risk of total invasive cancer and breast, colorectal and endometrial cancer in the Women's Health Study. 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.