A NESTED CASE-CONTROL STUDY OF PROSTATE CARCINOGENESIS

Henry Ford Health System, Detroit MI

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Abstract

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.