666 hypermethylated enhancer motifs were associated with prostate cancer (Additional file 11: Table S10) and the top three were SP2 (OR = 13.18, FDR Q-value = 5.4 × 10–286), SP1 (OR = 11.72, FDR Q-value = 3.1 × 10–312), and E2F4 (OR = 10.45, FDR Q-value < 2.2 × 10308) (Fig. 7D). Here, E2F4 is linked to Familial prostate cancer.