Abstract 5726: Association between human herpesvirus 8 infection, inflammation and a polymorphism in the IL-6 signaling receptor in increased prostate cancer risk among men of African descent

Abstract

Abstract Background: Prostate cancer is more prevalent among African Americans than Caucasians and this increased risk among men of African descent is not limited to the United States, suggesting a role for genetic or shared lifestyle factors. In our previous population-based study on the Caribbean island of Tobago, the prevalence of screening-detected prostate cancer was 3-fold higher compared to similarly screened US Caucasian men. The island of Tobago is 95% of African descent and represents a homogeneous population for studying genetic factors associated with disease. Inflammation has also been suggested as a co-factor for increased prostate cancer risk, and studies have demonstrated positive correlations with prostatitis and sexually transmitted diseases. We have previously reported an increased seroprevalence to human herpesvirus 8 (HHV-8) among Tobago men with prostate cancer (n=138) compared to Tobago age-matched controls (n=140; OR 2.24, 95% C.I. 1.29-3.90). In the current study we have expanded our earlier findings demonstrating an association between HHV-8 infection, inflammation and a polymorphism in the IL-6 signaling receptor gp130 in prostate cancer risk among men of African descent. Methods: Biopsies (n=19) and prostectomies (n=20) of Tobago men with histologically confirmed prostate cancer were analyzed by immunohistochemistry for expression of the HHV-8 proteins LANA-1, K8.1 or vIL-6 and the presence of B cells and macrophages. SNP analysis for the G148R polymorphism was performed on Tobago (n=1,217) and U.S. (n=149) men. Lymphoblastoid cell lines (LCLs) were constructed from Tobago men representing the three possible genotypes of the gp130 polymorphism (G148R; G/G, G/R and R/R). Growth curve analyses were performed on the LCLs grown in the absence or presence of 25ng/ml IL-6. Results: HHV-8 proteins were expressed in 75% of the prostate biopsies and 100% of the prostectomies of seropositive men. Viral protein expression was more prevalent in sections containing cancer compared to cancer free sections (p=0.001). Seropositive men who were homozygous for the R/R gp130 allele were significantly more likely to have prostate cancer than seronegative men who were homozygous for the G/G allele (n=400; OR 3.1, 95% C.I. 1.18-8.11). Increased inflammation (macrophage infiltration) in non-cancerous sections was associated with gp130 status (p=0.023). LCLs homozygous for the high risk gp130 allele demonstrated a 250% increase in growth compared to the homozygous low risk. Summary: Taken together, our results support the hypothesis that HHV-8 establishes a chronic infection producing chronic inflammation which, in association with a polymorphism in the IL-6 signaling receptor, results in increased prostate cancer risk among men of African descent in Tobago. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5726.