Genetic Epidemiology of Prostate Cancer Risk and Progression

前列腺癌风险和进展的遗传流行病学

• 批准号: 8870301
• 负责人: Stephen K. Van Den Eeden
• 金额: $ 44.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8870301
• 关键词: Address; Age; Clinical; Code; Collaborations; Complex; Computerized Medical Record; Custom; Data; Detection; Development; Diagnosis; Disease; Disease Progression; Environment; Ethnic Origin; Evaluation; Genes; Genetic; Genome; Genotype; Goals; Health; Heritability; Heterogeneity; Human Genome; Individual; Life; Malignant neoplasm of prostate; Measures; Mission; Modeling; Morbidity - disease rate; National Cancer Institute; Natural History; Open Reading Frames; Play; Population; Population Study; Prostatic Neoplasms; Research; Risk; Role; Sampling; Sampling Studies; Screening for Prostate Cancer; Structure of base of prostate; Testing; Time; Variant; base; cancer genetics; cancer risk; case control; cohort; disease natural history; disorder risk; exome; follow-up; genetic epidemiology; genetic variant; genome wide association study; genome-wide; improved; innovation; insight; male health; men; population health; predictive modeling; programs; rare variant; screening; tumor progression

DESCRIPTION (provided by applicant): Prostate cancer is a common but complex disease with a number of unresolved issues surrounding its natural history. These include concerns with screening, detection, and treatment, and reflect the substantial heterogeneity in prostate tumors: some will remain latent and have little impact on morbidity, whereas others progress rapidly in a potentially lethal manner. Genetic factors likely underlie some of these differences, and we propose a comprehensive evaluation of the genetic basis of prostate cancer risk and progression in a large, well-characterized study population. In particular, we will investigate rar functional variants across the exome and common SNPs across the genome. Our sample encompasses 8,078 prostate cancer cases and 8,078 age and ethnicity matched controls nested within the Kaiser / USCF Research Program on Genes, Environment and Health cohort. This population has existing genome-wide SNP measures, and uniformly collected clinical information on prostate cancer screening, diagnoses, and progression. We plan to type the new exome array on the cases and controls to assess the functional variants in protein coding regions across the human genome. With these data we will address our hypothesis that these genetic factors can be used to predict-and underlie an increasing proportion of the variation in-prostate cancer risk and progression. This project provides an efficient and innovative opportunity to obtain a comprehensive understanding of how these factors impact the natural history of prostate cancer. Our findings should supply important insights into the underlying mechanism of disease, with the ultimate goal of helping to improve screening and treatment for prostate cancer.

描述（由申请人提供）：前列腺癌是一种常见但复杂的疾病，围绕其自然史存在许多未解决的问题。这些包括对筛查、检测和治疗的关注，并反映了前列腺肿瘤的实质异质性：一些肿瘤将保持潜伏状态，对发病率影响不大，而另一些肿瘤则以潜在的致命方式迅速进展。遗传因素可能是其中一些差异的基础，我们建议在一个大型的、特征良好的研究人群中对前列腺癌风险和进展的遗传基础进行全面评估。特别是，我们将研究罕见的功能变异的外显子组和常见的单核苷酸多态性的基因组。我们的样本包括8，078例前列腺癌病例和8，078例年龄和种族匹配的对照组，这些对照组嵌套在Kaiser/USCF基因，环境和健康研究计划中。该人群具有现有的全基因组SNP测量，并统一收集有关前列腺癌筛查、诊断和进展的临床信息。我们计划在病例组和对照组上分型新的外显子组阵列，以评估整个人类基因组中蛋白质编码区的功能变体。有了这些数据，我们将阐明我们的假设，即这些遗传因素可用于预测前列腺癌的风险和进展，并成为前列腺癌风险和进展中变异比例增加的基础。该项目提供了一个有效和创新的机会，以全面了解这些因素如何影响前列腺癌的自然史。我们的发现应该为疾病的潜在机制提供重要的见解，最终目标是帮助改善前列腺癌的筛查和治疗。

项目成果

Prostate cancer susceptibility variants confer increased risk of disease progression.

• DOI: 10.1158/1055-9965.epi-10-0268
• 发表时间: 2010-09
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Cheng I;Plummer SJ;Neslund-Dudas C;Klein EA;Casey G;Rybicki BA;Witte JS
• 通讯作者: Witte JS

No association between genetic polymorphisms in insulin and insulin receptor substrate-1 and prostate cancer.

胰岛素和胰岛素受体底物 1 的遗传多态性与前列腺癌之间没有关联。

• DOI: 10.1158/1055-9965.epi-05-0531
• 发表时间: 2005
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.
• 作者: Li,Li;Cicek,MineS;Casey,Graham;Witte,JohnS
• 通讯作者: Witte,JohnS

Carboxypeptidase 4 gene variants and early-onset intermediate-to-high risk prostate cancer.

• DOI: 10.1186/1471-2407-9-69
• 发表时间: 2009-02-26
• 期刊: BMC cancer
• 影响因子: 3.8
• 作者: Ross PL;Cheng I;Liu X;Cicek MS;Carroll PR;Casey G;Witte JS
• 通讯作者: Witte JS

No association between a tetranucleotide repeat polymorphism of CYP19 and prostate cancer.

CYP19 的四核苷酸重复多态性与前列腺癌之间没有关联。

• 发表时间: 2004
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.
• 作者: Li,Li;Cicek,MineS;Casey,Graham;Witte,JohnS
• 通讯作者: Witte,JohnS

Strategies for Imputing and Analyzing Rare Variants in Association Studies.

• DOI: 10.1016/j.tig.2015.07.006
• 发表时间: 2015-10
• 期刊: Trends in genetics : TIG
• 作者: Hoffmann TJ;Witte JS
• 通讯作者: Witte JS