Prostate Cancer Studies

该项目包括分析和方法学研究，旨在评估前列腺癌的流行病学，并通过生化和方法学研究，澄清生活方式因素如何影响前列腺癌风险的生物学基础。我们的努力涉及到特殊人群中前列腺癌风险的各种环境、遗传和激素预测因素。我们在中国进行了一项多学科研究，评估低危人群前列腺癌的危险因素，以更清楚地了解前列腺癌风险存在较大种族差异的原因。这项研究收集了多个生物样本，主要目的是评估风险因素以及西方化如何影响前列腺癌的风险。这项研究还包括收集前列腺癌肿瘤的组织样本，以实现准确的肿瘤分类以及肿瘤生物标志物的分析，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，并与对照组进行比较，以评估中国的西式饮食是否与前列腺癌风险过高有关。这项研究还在评估西方化的生物学相关性，以寻找西方化和过度前列腺癌风险之间的潜在生物学联系。有关荷尔蒙的基因型和循环水平的数据为研究血清荷尔蒙和遗传变异之间的相互关系提供了一个独特的机会，以深入了解这些遗传标记的功能意义。在另一项在中国15个城市进行的前列腺癌研究中，我们正在通过制定饮食异黄酮指数来评估大豆在前列腺癌中的作用。非洲加纳目前正在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。这项研究将收集过去5年中500多名被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1038名健康男性进行前列腺癌筛查，以评估西非男性前列腺癌的负担。从这1038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、激素和基因图谱提供独特的资源。此外，将这1038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的西方化是否与不良代谢特征(肥胖、腹型肥胖、较高水平的胰岛素、低密度脂蛋白和胰岛素样生长因子I)有关，后者与前列腺癌风险过高有关。我们进一步扩大了病例招募范围，将另外500例癌症病例纳入全基因组关联研究(GWAS)。我们最近对8q24区域进行了测序，并在该区域发现了几个新的变异体。在包括前列腺癌、肺癌、结直肠癌和卵巢癌(PLCO)筛查试验、前列腺癌预防试验(PCPT)和美国癌症协会营养队列(CPS-II)在内的几项大型队列嵌套病例对照研究中，我们正在评估肥胖、饮食结构、胰岛素抵抗和慢性炎症与前列腺癌后续风险的关系，其中包括三项前瞻性研究，这些队列共同提供了3000多例前列腺癌病例，用于前列腺癌病因的研究。他们的独特之处在于，随着时间的推移，他们收集了疾病前的血液和多种生物样本，从而能够评估随着患者接近诊断，激素和其他生物标记物水平如何变化。目前正在进行一项方法学研究，以评估循环中的雄激素水平是否反映了前列腺内的雄激素生成，这是前列腺癌激素致癌的关键问题。这项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(超过3000块)的样本。这项研究的数据将提供一个独特的机会来研究血清和组织激素以及雄激素代谢途径中涉及的基因变异之间的相互关系，为确定这些遗传标记的功能意义提供关键数据。组织样本的收集也将为基因表达研究提供一个独特的机会。

This project includes 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 prostate cancer 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. That study involved the 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 involved the collection of tissue samples from prostate cancer tumors 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 and compared with those of controls to evaluate whether a western-style 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 500 men diagnosed with prostate cancer during the last 5 years and screen 1,038 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 1,038 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, 038 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 has been associated with excess prostate cancer risk. We further expand case recruitment to include an additional 500 cancer cases for a genome wide association study (GWAS). We have recently sequenced the 8q24 region and identified several novel variants in this region. In several nested case-control studies in large cohorts, including Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, and the Prostate Cancer Prevention Trial (PCPT), and the American Cancer Society Nutrition Cohort (CPS-II), we are assessing the relationships of obesity, dietary patterns, insulin resistance, and chronic inflammation with subsequent risk of prostate cancer in three prospective studies, including the Together, these cohorts provide over 3,000 prostate cancer cases for the investigation of prostate cancer etiology. They are 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. 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 3,000 pieces) from 600 study subjects in three racial/ethnic groups. Data from this study will provide a unique opportunity to investigate the interrelationships among serum and tissue hormones and variants in genes involved in the androgen metabolism pathways to provide critical data for determining the functional significance of these genetic markers. The collection of tissue samples also will provide a unique opportunity for gene expression studies.