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.

慢性感染是由感染剂或暴露于环境因素引起的 据信，例如杂环胺在20％的成年癌症中发挥作用。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 参与癌症发展，但这些数据与流行病学研究的结果相冲突 这表明炎症与前列腺癌风险之间存在反相关性。这可能到期 偏向导致男性进行前列腺活检的因素，以及 炎症表型本身。 我们提出的研究将通过在细胞上剖析创新来解决这一悖论， 分子和临床水平。亨利·福特卫生系统生物座位包含良性 在过去20年中，从9,000多名男性收集的前列腺组织标本，包括 1,000名随后患上前列腺癌的男性。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700的嵌套病例对照研究 前列腺癌病例对照对。在这些前疾病中表征炎症标记 标本将使我们能够确定“肿瘤抑制”与“肿瘤支持”的性质 炎症签名。我们还将在同一良性前列腺中测量端粒长度 我们表征注射以分配“恶性潜能的组织样本 每个标本的签名”。 每年在美国进行大约100万个前列腺活检 揭示良性状况。我们的队列包括一大批患者 前列腺癌目的地进行阴性活检。深入的炎症表征 良性前列腺，在组织学迹象变得明显之前，将提供有关 与最终肿瘤发展以及癌症相关的炎症环境类型 进展和复发。更好地理解慢性的临床意义 前列腺的炎症 - 经常在老年男性中观察到 - 可能会对 数以百万计的男性目前进行阴性活检，就前列腺而言几乎没有放心 癌症的结果。

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.

• 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