Stefan Ambs

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PLCO (Learn more about this study)

2009-0552

Dec 15, 2009

Association of Human Endogenous Retrovirus K (HERV-K) Expression with Prostate Cancer Development and Progression

Research in our laboratory discovered a distinct gene signature in prostate tumors of African-American patients consistent with either a viral infection or reactivation of endogenous retroviruses in the tumor microenvironment 1. Human endogenous retroviral sequences (HERVs) comprise ~8% of our genome 2. Their reactivation has been observed in several human cancers 3-5. Of all known HERVs, HERV-K is the most intact and transcriptionally active endogenous retrovirus and can trigger an immune response 2,3,6. Expression differences for HERV-K amongst ethnic groups have been described, with some polymorphic HERV-K sequences being most frequently expressed in African populations 7. Given the association of HERV-K with human cancer and expression differences by ancestry, we investigated the association of HERV-K expression with prostate cancer in European-American and African-American men. In a pilot case-control study, HERV-K expression was evaluated from buffy coat in 294 prostate cancer cases and 135 population-based controls. This study found HERV-K to be significantly associated with prostate cancer in a dose-dependent manner among both African-American and European-American men. Furthermore, African-American controls had significantly higher HERV-K expression than European-American controls. The data suggest that HERV-K expression could be an unrecognized and significant pre-disposing factor in prostate cancer, or a disease effect. Because pre-diagnostic samples were not available in the pilot, we could not determine whether HERV-K expression precedes disease development. In any case, the findings from the pilot are novel and significant, and should be pursued in a larger setting. In this proposal, we aim to validate the association of HERV-K with prostate cancer. Moreover, we propose to investigate pre-diagnostic samples to determine if reactivation of HERV-K is a risk factor and marker of prostate cancer that precedes diagnosis. Finally, we propose to analyze HERV-K expression in early and advanced prostate cancer to examine whether the HERV-K burden increases with disease progression.