Prostate Cancer Studies

前列腺癌研究

• 批准号: 9339162
• 负责人: Michael Cook
• 金额: $ 67.69万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9339162
• 关键词: 8q24; Africa; African; Age; Androgen Metabolism; Androgens; Biochemical; Biological; Biological Assay; Biological Markers; Blood; Burkitt Lymphoma; Case Series; Central obesity; China; Cities; Classification; Clinical; Collection; Colorectal; Consent; Data; Databases; Diagnosis; Diet; Dietary Factors; Dietary Practices; Epidemiology; Ethnic group; Fasting; Freezing; Fresh Tissue; Gene Expression; Genes; Genetic; Genetic Markers; Genotype; Ghana; Health; Hormonal; Hormonal Carcinogenesis; Hormones; Human; Human Genetics; Insulin; Insulin-Like Growth Factor I; Interview; Isoflavones; Life Style; Link; Low-Density Lipoproteins; Lung; Malaria; Malignant neoplasm of prostate; Manuscripts; Maps; Medicare; Meta-Analysis; Molecular; Molecular Genetics; Nature; Nested Case-Control Study; Non-Steroidal Anti-Inflammatory Agents; Nutritional; Obesity; Outcome; Ovarian; Pathway interactions; Pharmaceutical Preparations; Population; Predisposition; Prevalence; Prostate; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Prostatic Diseases; Publishing; Questionnaires; Recruitment Activity; Recurrence; Research; Resources; Risk; Risk Factors; Role; Sampling; Series; Serum; Stage at Diagnosis; Staining method; Stains; Study Subject; Surveys; TMPRSS2 gene; Techniques; Testosterone; Time; Tissue Microarray; Tissue Sample; Tissues; Tumor Markers; Variant; base; cancer risk; cancer type; case control; clinical practice; clinically relevant; cohort; design; follow-up; genetic profiling; genetic risk factor; genetic variant; genome wide association study; indexing; insight; men; metabolic profile; mortality; multidisciplinary; novel; population based; population survey; racial and ethnic; racial difference; resistance gene; soy; tumor

In Ghana, Africa, we have conducted a population-based survey of men to assess the population prevalence of prostatic disease (CAS ID:01130). We have also collected consented into the study a clinical series of men diagnosed with prostate cancer. This dynamic epidemiologic design of a population survey combined with a larger case series, is enabling us to assess the burden of prostate cancer in African men as well as assess risk factors associated with prostate cancer in an important and understudied population. Biological samples collected from the 1,038 healthy men in the population survey component will allow us to establish the nutritional, hormonal, and genetic profiles of African men. In addition, linking interview data from these 1,038 healthy subjects with biomarkers 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. The additional 677 prostate cancer cases that we recruited through the clinical component has enabled us to conduct a genome wide association study (GWAS) of prostate cancer in this unique population (published in Human Genetics). In addition, we have sequenced the 8q24 region and identified several novel variants (published in Prostate) as well contributed to a pooled fine-mapping study of this region in African Men (published in JNCI) and an imputation and subset based meta-analysis of chr5p15.33 across multiple cancer types (published in Human Molecular Genetics). We have also contributed data to multi-racial GWAS and have identified 23 novel genetic (SNP) associations with prostate cancer (published in Nature Genetics). We have recently contributed to an integrative analysis to identify candidate functional SNPs at prostate cancer susceptibility regions of the geonome (published in Human Molecular Genetics). We are now extending this GWAS effort to include additional cases and controls that were recruited for this study. We are also using the population component of the Ghana Prostate Study to assess the prevalence of malaria-resistance genes with a view to uncovering the genetic risk factors of Burkitt lymphoma in Africa. We are assessing whether IFNL4 is also prominent in African men by genotyping the IFNL4 variant in 350 population-based controls in the Ghana Prostate Study. We are also assessing whether this variant can be imputed using the existing GWAS data. We are assessing whether IFNL4 is associated with age and/or stage at diagnosis of prostate cancer in the Ghana Prostate Study. We are also currently assessing the prevalence of TMPRSS2-ERG fusions in prostate cancer tissues of these African prostate cancer cases (manuscript being drafted). We have also begun analyses of questionnaire components of this study to further elucidate associations of prostate cancer in this novel population. 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 (CAS ID:01140). 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 microarray 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. In addition, several nested case-control studies in large cohorts, including Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, the SEER-Medicare database, total Medicare, and Clinical Practice Research Datalink (CPRD) we are assessing the relationships of hormone-related factors with subsequent risks of prostate cancer and prostate cancer-specific mortality. 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 (CAS ID:01072). This methodologic study has collected 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. This manuscript is currently being drafted.In continuing the theme of hormonal perturbations in relation to prostate cancer, we are also using a large health database to assess whether testosterone replacement medications are associated with prostate cancer risk (CAS ID: 10667). For more accurate and detailed follow up in PLCO to enable prostate recurrence analyses and analyses of outcomes post-diagnosis in this resource, we are currently extending the follow-up time beyond the first year post-diagnosis to capture all clinically relevant data (CAS ID: 10515). Biochemical recurrence is being assessed in relation to tissue IHC stains.Lastly, we are using data from AARP to investigate the association of NSAID use and subsequent risk of cancer, including prostate cancer (CAS ID: 10547), the manuscript of which is currently under review.

在非洲加纳，我们进行了基于人群的男性调查，以评估前列腺疾病的人口流行（CAS ID：01130）。我们还收集了一系列诊断为前列腺癌的临床男性。这种人口调查的这种动态流行病学设计与较大的病例系列相结合，使我们能够评估非洲男性前列腺癌的负担，并评估重要且研究不足的人群中与前列腺癌相关的危险因素。从1,038名健康男性中收集的生物样品中，在人口调查部分中，我们可以建立非洲男性的营养，荷尔蒙和遗传特征。此外，将这1,038名健康受试者与生物标志物的访谈数据联系起来将产生有关非洲男性西方化是否与不良代谢概况有关（肥胖；腹部肥胖；较高的胰岛素，低密度脂蛋白和胰岛素样生长因子的较高水平）与前列腺癌危害过多相关。我们通过临床成分招募的另外677例前列腺癌病例使我们能够在这种独特的人群中（人类遗传学发表）进行一项基因组广泛关联研究（GWAS）。此外，我们已经对8Q224区域进行了测序，并确定了几种新型变异（以前列腺出版），并有助于对非洲男性（JNCI发表）的该区域进行了汇总的精细映射研究，以及基于多种癌症的CHR5P15.33的基于插款和子集的荟萃分析（发表在人类分子遗传学中）。我们还为多种族GWA提供了数据，并确定了23种新型遗传（SNP）与前列腺癌（发表在自然遗传学中）。我们最近为综合分析做出了贡献，旨在鉴定Geonome的前列腺癌敏感性区域（发表在人分子遗传学上）的候选功能SNP。现在，我们正在扩大这种GWAS的努力，以包括为这项研究招募的其他案例和控制。我们还使用加纳前列腺研究的种群成分来评估疟疾抵抗基因的流行，以发现非洲伯基特淋巴瘤的遗传危险因素。我们正在通过在加纳前列腺研究中基于350个基于人群的对照组中的IFNL4变体来评估非洲男性中的IFNL4是否也很突出。我们还在评估是否可以使用现有的GWAS数据来估算此变体。我们正在评估在加纳前列腺研究中，IFNL4是否与前列腺癌诊断为年龄和/或阶段有关。我们目前还评估了这些非洲前列腺癌病例的前列腺癌组织中TMPRSS2-ERG融合的患病率（草稿）。我们还开始对这项研究的问卷分量进行分析，以进一步阐明这一新人群中前列腺癌的关联。我们在中国进行了一项多学科研究，以评估低风险人群中前列腺癌的危险因素，以便更清楚地了解前列腺癌风险种族差异的原因（CAS ID：01140）。该研究涉及收集多种生物样品，其主要目的是评估危险因素以及西方化如何影响前列腺癌的风险。该研究还涉及从前列腺癌肿瘤收集的组织样品，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，并将其与对照组的饮食模式进行比较，以评估中国的西方饮食是否与前列腺癌的过量风险有关。该研究还评估了西方化的生物学相关性，以寻找西方化与前列腺过量癌症风险之间的潜在生物学联系。基因型和激素循环水平的数据为研究血清激素和遗传变异的相互关系提供了独特的机会，以洞悉这些遗传标记的功能意义。在中国15个城市的另一项关于前列腺癌的研究中，我们正在通过开发饮食中异黄酮指数来评估大豆在前列腺癌中的作用。此外，在包括前列腺，肺，结直肠和卵巢癌（PLCO）癌症筛查试验的大型队列中进行了一些嵌套的病例对照研究，SEER-MEDICARE数据库，Medicare Total Medicare和临床实践研究数据链接（CPRD），我们正在评估与随后的癌症癌症和促销癌症的关系的关系。 目前正在进行一项方法论研究，以评估循环水平的雄激素是否反映了脑内雄激素，这是前列腺激素致癌作用的关键问题（CAS ID：01072）。这项方法学研究收集了三个种族/族裔群体中600名研究对象的空腹血液和快速冻结的新鲜组织（超过3,000张）。这项研究的数据将提供一个独特的机会，以研究血清和组织激素之间的相互关系以及与雄激素代谢途径有关的基因中的变体，以提供关键数据，以确定这些遗传标记的功能意义。组织样品的收集还将为基因表达研究提供独特的机会。该手稿目前正在起草。在继续与前列腺癌相关的激素扰动的主题，我们还使用大型健康数据库来评估睾丸激素替代药物是否与前列腺癌风险有关（CAS ID：10667）。为了在PLCO中进行更准确，更详细的随访，以实现该资源诊断后结果的前列腺复发分析和分析，我们目前将后续时间延长到诊断后第一年以上，以捕获所有临床相关的数据（CAS ID：CAS ID：10515）。正在评估与组织IHC染色有关的生化复发。极度地，我们使用AARP的数据来研究NSAID使用和随后发生癌症的风险，包括前列腺癌（CAS ID：10547），目前正在审查其手稿。