A NESTED CASE-CONTROL STUDY OF PROSTATE CARCINOGENESIS

慢性炎症，由感染性病原体或暴露于环境因素引起 例如杂环胺，据信在高达20%的成人癌症中起作用。在前列腺中， 遗传学、分子病理学和毒理学数据表明，炎症相关的过程 参与了癌症的发展，但这些数据与流行病学研究的结果相冲突 这表明炎症和前列腺癌风险之间存在负相关。这可能是由于 对导致男性接受前列腺活检的因素以及前列腺活检的复杂性存在偏见 炎症表型本身。 我们提出的研究将通过解剖细胞内的炎症来解决这一悖论， 分子水平和临床水平。亨利·福特健康系统生物资源库包含良性 在过去的20年里，从9000多名男性身上收集了前列腺组织样本，其中包括 1000名男性随后患上前列腺癌。使用这个独特的队列和它的 在注解临床基线和随访数据后，我们将对700名患者进行嵌套病例对照研究 前列腺癌病例对照配对。这些疾病前期的炎性标志物的特征 标本将使我们能够确定“肿瘤抑制”与“肿瘤支持”的性质。 具有煽动性的特征。我们还将测量同一良性前列腺的端粒长度。 我们将炎症定性为“恶性潜能”的组织标本 每一份标本都有“签名”字样。 在美国，每年大约有100万例前列腺活检，其中三分之二 显示情况良好。我们的队列包括一大群有高风险的患者 前列腺癌，尽管活检结果为阴性。对炎症的深入描述 良性前列腺，在组织学恶性迹象变得明显之前，将提供对 与最终的肿瘤发展和癌症有关的炎症环境的类型 进展性和复发性。更好地了解慢性阻塞性肺疾病的临床意义 前列腺炎--通常在老年男性中观察到--可能对 数以百万计的男性，目前的阴性活检在前列腺方面几乎不能保证 癌症后果。

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.