Methylation of global DNA repeat LINE-1 and subtelomeric DNA repeats D4Z4 in leukocytes is associated with biochemical recurrence in African American prostate cancer patients

Global DNA methylation may play important roles in cancer etiology and prognosis. The goal of this study is to investigate whether the methylation of long interspersed nucleotide elements (LINE-1) and subtelomeric DNA repeats D4Z4 in leukocyte DNA is associated with aggressive prostate cancer (PCa) in African Americans. We measured DNA methylation levels of LINE-1 and D4Z4 in 306 African American (AA) PCa patients using pyrosequencing and compared their methylation levels among clinical variables. We further applied multivariate Cox proportional hazards model and Kaplan-Meier survival function and log-rank tests to assess the association between DNA methylation and biochemical recurrence (BCR). Overall, there was no significant difference of the methylation levels of LINE-1 and D4Z4 among patients with different clinical and epidemiological characteristics. However, the methylation of LINE-1 and D4Z4 was associated with BCR. Patients with lower LINE-1 methylation and higher D4Z4 methylation exhibited markedly increased risks of BCR with adjusted hazard ratios of 3.34 (95% confidence interval, 1.32-8.45) and 4.12 (95% confidence interval, 1.32-12.86), respectively, and significantly shorter BCR-free survival times. Our results suggest that lower global DNA methylation and higher subtelomeric region methylation may predict worse prognosis in localized AA PCa patients.