The role of cytomegalovirus in prostate cancer incidence and mortality

Abstract

ABSTRACTProstate cancer is one of the most common cancers in men with over 350 000 prostate cancer deaths reported worldwide every year. Current risk stratification models are insufficient to predict prostate cancer and prostate cancer death. New biomarkers are needed to identify those at increased risk of lethal prostate cancer. Cytomegalovirus (CMV) infection is common in the healthy prostate epithelium and promotes cell proliferation and viability in prostate cancer. Analyzing matched serum and tissue samples from post-mortem donors (n=41) and prostate cancer patients (n=40), we report that CMV seropositivity predicts high CMV abundance in prostate tissue. We studied if CMV seropositive men had increased prostate cancer incidence and cancer mortality in the European Prospective Investigation of Cancer (EPIC)–Norfolk population-based cohort study. CMV IgG serostatus was determined between 1993 and 2000 in 7,655 men aged 40-81 years, of which 57% were CMV seropositive. Study participants were followed for 18±6.0 years (mean±SD). We used Cox proportional hazard models, adjusted for age and potential confounders to estimate hazard ratios (HR) with 95% confidence intervals (CI). CMV serostatus was not associated with prostate cancer incidence (adjusted HR 1.03, 95% CI 0.89-1.19, p=0.687, 138,652 person-years). However, among prostate cancer patients, CMV seropositivity was associated with increased risk of prostate cancer-associated mortality (adjusted HR 2.26, CI 95% 1.02-4.99, p=0.044, 4639 person-years), with 25% of seropositive and 18% of seronegative prostate cancer patients dying from their disease during follow up. These results show that CMV seropositivity is associated with increased risk of prostate cancer death and suggest that CMV infection may contribute to prostate cancer lethality.