Prostate Cancer Studies

该项目包括旨在评估前列腺癌流行病学的分析和方法学研究，并通过生化和方法学研究阐明生活方式因素如何影响前列腺癌风险的生物学基础。我们的研究涉及特殊人群中各种环境、遗传和激素的风险预测因素。我们在中国开展了一项多学科研究，在低危人群中评估前列腺癌的危险因素，以便更清楚地了解前列腺癌风险存在较大种族差异的原因。该研究收集了多种生物样本，主要目的是评估风险因素以及西化如何影响前列腺癌的风险。该研究还涉及组织样本的收集，以允许精确的肿瘤分类以及肿瘤生物标志物的测定，在某些情况下使用新开发的组织微阵列技术。除了特定的饮食因素外，还将确定饮食模式，以评估中国的西式饮食模式是否与前列腺癌风险过高有关。该研究还评估了西化的生物学相关性，以寻找西化与前列腺癌过度风险之间的潜在生物学联系。基因型和循环激素水平的数据提供了一个独特的机会来研究血清激素和遗传变异之间的相互关系，以深入了解这些遗传标记的功能意义。在另一项针对中国15个城市前列腺癌的研究中，我们正在通过制定膳食异黄酮指数来评估大豆在前列腺癌中的作用。目前正在非洲加纳进行一项以人口为基础的调查，以评估非洲男性前列腺癌的负担。本研究将收集过去5年中1000多名诊断为前列腺癌的男性的临床/病理数据，并通过直肠指检和前列腺特异性抗原对1000名健康男性进行前列腺癌筛查，以评估西非男性前列腺癌负担。从这1000名健康男性身上收集的生物样本将为建立非洲男性的营养、荷尔蒙和基因图谱提供独特的资源。此外，将这1000名健康受试者的访谈数据与他们的生物标志物联系起来，将有助于深入了解非洲男性西化是否与不良代谢特征（肥胖、腹部肥胖、胰岛素水平较高、低密度脂蛋白和胰岛素样生长因子I）有关，这些代谢特征与前列腺癌风险过高有关。我们也正在评估肥胖、饮食模式、胰岛素抵抗和慢性炎症与前列腺癌后续风险的关系，这是在前列腺、肺、结直肠和卵巢（PLCO）癌症筛查试验的病因学组成部分。该资源的独特之处在于，随着时间的推移，它收集了发病前的血液和多种生物样本，允许评估激素和其他生物标志物水平在患者接近诊断时的变化。我们正在与美国癌症协会的研究人员合作，对1200例前列腺癌病例和1200例对照进行巢式病例对照研究，以调查胰岛素抵抗、肥胖、炎症和血管生成的遗传易感性在前列腺癌风险中的作用。目前正在进行一项方法学研究，以评估循环雄激素水平是否反映前列腺内雄激素性，这是前列腺激素致癌的一个关键问题。本方法学研究将收集来自三个种族/民族的600名研究对象的空腹血液和速冻新鲜组织样本（超过4000份）。

This project covers analytic and methodologic studies aimed at assessing the epidemiology of prostate cancer and clarifying through biochemical and methodologic studies the biological underpinnings of how lifestyle factors influence the risk of prostate cancer. Our efforts relate to a variety of environmental, genetic, and hormonal predictors of risk in special populations. We have conducted a multidisciplinary study in China to assess risk factors for prostate cancer in a low-risk population in order to understand more clearly the reasons for the large racial differences in prostate cancer risk. The study involves collection of multiple biologic samples, with a primary aim of assessing risk factors and how westernization influences the risk of prostate cancer. The study also involves collection of tissue samples to permit precise tumor classification as well as assays of tumor biomarkers, in some cases using newly developed tissue micro array techniques. In addition to specific dietary factors, dietary patterns will be identified to evaluate whether a western-pattern diet in China is related to excess, prostate cancer risk. The study is also assessing biological correlates of westernization to look for potential biological links between westernization and excess prostate cancer risk. Data on genotypes and circulating levels of hormones provide a unique opportunity to investigate the interrelationships between serum hormones and genetic variants to gain insights into the functional significance of these genetic markers. In another study of prostate cancer in 15 cities in China, we are assessing the role of soy in prostate cancer by developing a dietary isoflavone index. A population-based survey is currently underway in Ghana, Africa, to assess the burden of prostate cancer in African men. This study will collect clinical/pathological data from over 1,000 men diagnosed with prostate cancer during the last 5 years and screen 1,000 healthy men for prostate cancer by digital rectal examination and prostate specific antigen to evaluate the burden of prostate cancer in west African men. Biological samples collected from these 1,000 healthy men will provide a unique resource to establish the nutritional, hormonal, and genetic profiles of African men. In addition, linking interview data from these 1, 000 healthy subjects with biomarkers from them will produce insights into whether westernization in African men is associated with an adverse metabolic profile (obesity , abdominal obesity , higher levels of insulin, low-density lipoprotein, and insulin-like growth factor I), which have been associated with excess prostate cancer risk. We also are assessing the relationships of obesity, dietary patterns, insulin resistance, and chronic inflammation with subsequent risk of prostate cancer within the etiologic component of the large Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. This resource is unique in having collected pre-morbid blood and multiple biologic samples over time, permitting an assessment of how hormone and other biomarker levels change as patients approach diagnosis. We are collaborating with investigators from the American Cancer Society in a nested case-control study of 1200 prostate cancer cases and 1200 controls to investigate the role of genetic susceptibility to insulin resistance, obesity, inflammation, and angiogenesis on prostate cancer risk. A methodologic study is currently underway to evaluate whether circulating levels of androgens reflect intraprostatic androgenicity, a key issue in hormonal carcinogenesis of the prostate. This methodologic study will collect samples of fasting blood and snap-frozen fresh tissue (over 4000 pieces) from 600 study subjects in three racial/ethnic groups.