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.
Approximately 1 million prostate biopsies are performed annually in the US, two-thirds of which reveal benign conditions, but often with histologic inflammation. The proposed study seeks to clarify the role of histologic inflammation in the development of prostate cancer thereby providing targets for prevention and treatment.
|Rundle, Andrew; Wang, Yun; Sadasivan, Sudha et al. (2017) Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk. Prostate 77:949-954|
|Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb et al. (2016) Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. Nat Commun 7:10979|
|Han, Ying; Rand, Kristin A; Hazelett, Dennis J et al. (2016) Prostate Cancer Susceptibility in Men of African Ancestry at 8q24. J Natl Cancer Inst 108:|
|Rand, Kristin A; Rohland, Nadin; Tandon, Arti et al. (2016) Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk. Hum Mol Genet 25:371-81|
|Rand, Kristin A; Song, Chi; Dean, Eric et al. (2016) A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci. Cancer Epidemiol Biomarkers Prev 25:1609-1618|
|Rybicki, Benjamin A; Rundle, Andrew; Kryvenko, Oleksandr N et al. (2016) Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer. Int J Cancer 138:2884-93|
|Rybicki, B A; Kryvenko, O N; Wang, Y et al. (2016) Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer. Prostate Cancer Prostatic Dis 19:145-50|
|Helfand, Brian T; Roehl, Kimberly A; Cooper, Phillip R et al. (2015) Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases. Hum Genet 134:439-50|
|Barber, Alison G; Castillo-Martin, Mireia; Bonal, Dennis M et al. (2015) PI3K/AKT pathway regulates E-cadherin and Desmoglein 2 in aggressive prostate cancer. Cancer Med 4:1258-71|
|Han, Ying; Signorello, Lisa B; Strom, Sara S et al. (2015) Generalizability of established prostate cancer risk variants in men of African ancestry. Int J Cancer 136:1210-7|
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