A NESTED CASE-CONTROL STUDY OF PROSTATE CARCINOGENESIS

前列腺癌发生的巢式病例对照研究

• 批准号: 9304223
• 负责人: Benjamin A. Rybicki
• 金额: $ 47.33万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9304223
• 关键词: Address; Adult; Atrophic; B-Lymphocytes; Benign; Biological Markers; Biopsy; Chronic; Clinical; Conflict (Psychology); Data; Development; Disease; Environment; Environmental Risk Factor; Exposure to; Genetic; Health system; Heterocyclic Amines; Histologic; Incidence; Infectious Agent; Inflammation; Inflammatory; Lead; Length; Leucocytic infiltrate; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Molecular; Nature; Nested Case-Control Study; Outcome; Patients; Phenotype; Play; Prevention; Process; Prostate; Prostatic; Recurrence; Risk; Role; Specimen; T-Lymphocyte; Tissues; Toxicology; Tumorigenicity; biobank; cancer recurrence; cancer risk; case control; cohort; cytokine; epidemiology study; follow-up; high risk; inflammatory marker; inflammatory milieu; insight; macrophage; men; molecular pathology; older men; prostate biopsy; prostate carcinogenesis; telomere; tumor; tumor progression; tumorigenic

Chronic inflammation, which is caused by infectious agents or exposure to environmental factors such as heterocyclic amines, is believed to play a role in up 20% of adult cancers. In prostate, genetic, molecular pathology, and toxicology data suggest that inflammation-related processes are involved in cancer development, but these data conflict with results of epidemiological studies that show an inverse correlation between inflammation and prostate cancer risk. This may be due to bias in the factors that lead men to undergo prostate biopsy, as well as complexity of the inflammatory phenotype itself. Our proposed study will address this paradox by dissecting inflammation at the cellular, molecular, and clinical level. The Henry Ford Health System biorepository contains benign prostate tissue specimens collected from over 9,000 men over the past 20 years, including over 1,000 men who subsequently developed prostate cancer. Using this unique cohort with its annotated clinical baseline and follow-up data, we will conduct a nested case-control study of 700 prostate cancer case-control pairs. Characterizing inflammatory markers in these pre-disease specimens will allow us to determine the nature of “tumor-suppressive” vs. “tumor-supportive” inflammatory signatures. We will also measure telomere length in the same benign prostate tissue specimens in which we characterize inflammation to assign a “malignancy-potential signature” to each specimen. Approximately 1 million prostate biopsies are performed annually in the US, twothirds of which reveal benign condition. Our cohort includes a large group of patients who are at high risk of prostate cancer despite a negative biopsy. An in-depth characterization of inflammation in the benign prostate, before histologic signs of malignancy become apparent, will provide insight into the type of inflammatory milieu associated with eventual tumor development as well as cancer progression and recurrence. A better understanding of the clinical implications of chronic inflammation of the prostate – so often observed in older men – can have significant impact upon millions of men where currently a negative biopsy offers little reassurance in terms of prostate cancer outcomes.

慢性炎症，由感染因子或暴露于环境因素引起 例如杂环胺，被认为在高达20%的成人癌症中起作用。在前列腺中， 遗传、分子病理学和毒理学数据表明，炎症相关过程 与癌症的发展有关，但这些数据与流行病学研究的结果相矛盾。 表明炎症和前列腺癌风险之间存在负相关。这可能是由于 在导致男性接受前列腺活检的因素中存在偏见，以及 炎症表型本身。 我们提出的研究将通过解剖细胞中的炎症来解决这个矛盾， 分子水平和临床水平。亨利福特健康系统生物储存库含有良性 在过去的20年里，从9,000多名男性身上收集了前列腺组织标本，其中包括 1,000名男性随后患上前列腺癌。使用这个独特的队列， 注释的临床基线和随访数据，我们将进行一项巢式病例对照研究， 前列腺癌病例对照对。表征这些疾病前的炎症标志物 标本将使我们能够确定“肿瘤抑制”与“肿瘤支持”的性质， 炎症信号我们还将测量同一良性前列腺中的端粒长度 组织标本，我们在其中表征炎症，以分配“恶性潜能 签名”，每个样本。 在美国，每年进行大约100万次前列腺活检，其中三分之二的前列腺活检是由前列腺活检引起的。 显示为良性我们的队列包括一大群处于高风险的患者， 尽管活检结果是阴性对炎症的深入描述 良性前列腺，在恶性肿瘤的组织学体征变得明显之前，将提供对 与最终肿瘤发展以及癌症相关的炎性环境类型 进展和复发。更好地理解慢性胰腺炎的临床意义 前列腺炎症-在老年男性中经常观察到-可以对 目前，数百万男性的前列腺活检结果为阴性， 癌症结果。

项目成果

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

• DOI: 10.1038/pcan.2015.54
• 发表时间: 2016-06
• 期刊: Prostate cancer and prostatic diseases
• 影响因子: 4.8
• 作者: Rybicki BA;Kryvenko ON;Wang Y;Jankowski M;Trudeau S;Chitale DA;Gupta NS;Rundle A;Tang D
• 通讯作者: Tang D

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts in benign prostate and subsequent risk for prostate cancer.

2-Amino-1-甲基-6-苯基咪唑唑[4,5-B]吡啶（PHIP） - 良性前列腺中的DNA加合物，后来患前列腺癌的风险。

• DOI: 10.1002/ijc.28092
• 发表时间: 2013-08-15
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Tang, Deliang;Kryvenko, Oleksandr N.;Wang, Yun;Trudeau, Sheri;Rundle, Andrew;Takahashi, Satoru;Shirai, Tomoyuki;Rybicki, Benjamin A.
• 通讯作者: Rybicki, Benjamin A.

Red wine consumption is inversely associated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-DNA adduct levels in prostate.

• DOI: 10.1158/1940-6207.capr-11-0100
• 发表时间: 2011-10
• 期刊: Cancer prevention research (Philadelphia, Pa.)
• 作者: Rybicki BA;Neslund-Dudas C;Bock CH;Nock NL;Rundle A;Jankowski M;Levin AM;Beebe-Dimmer J;Savera AT;Takahashi S;Shirai T;Tang D
• 通讯作者: Tang D

Racial differences in the systemic inflammatory response to prostate cancer.

• DOI: 10.1371/journal.pone.0252951
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Rundle AG;Sadasivan SM;Chitale DA;Gupta NS;Williamson SR;Kryvenko ON;Chen Y;Bobbitt K;Tang D;Rybicki BA
• 通讯作者: Rybicki BA

Elevated polycyclic aromatic hydrocarbon-DNA adducts in benign prostate and risk of prostate cancer in African Americans.

• DOI: 10.1093/carcin/bgs326
• 发表时间: 2013
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: D. Tang;Oleksandr N. Kryvenko;Yun Wang;M. Jankowski;S. Trudeau;A. Rundle;B. Rybicki