Chronic inflammation, which is caused by infectious agents or exposure to environmental factorssuch 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 processesare involved in cancer development, but these data conflict with results of epidemiological studiesthat show an inverse correlation between inflammation and prostate cancer risk. This may be dueto bias in the factors that lead men to undergo prostate biopsy, as well as complexity of theinflammatory 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 benignprostate tissue specimens collected from over 9,000 men over the past 20 years, including over1,000 men who subsequently developed prostate cancer. Using this unique cohort with itsannotated clinical baseline and follow-up data, we will conduct a nested case-control study of 700prostate cancer case-control pairs. Characterizing inflammatory markers in these pre-diseasespecimens 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 prostatetissue specimens in which we characterize inflammation to assign a “malignancy-potentialsignature” to each specimen.Approximately 1 million prostate biopsies are performed annually in the US, twothirds of whichreveal benign condition. Our cohort includes a large group of patients who are at high risk ofprostate cancer despite a negative biopsy. An in-depth characterization of inflammation in thebenign prostate, before histologic signs of malignancy become apparent, will provide insight intothe type of inflammatory milieu associated with eventual tumor development as well as cancerprogression and recurrence. A better understanding of the clinical implications of chronicinflammation of the prostate – so often observed in older men – can have significant impact uponmillions of men where currently a negative biopsy offers little reassurance in terms of prostatecancer outcomes.