Genome-wide DNA methylation profiling of prostate specimens from a clinical trial of genistein supplementation prior to prostatectomy.

To identify molecular effects of genistein on DNA methylation in prostate cancer, we compared DNA methylation profiles of genistein-treated tumors with placebo-treated samples. There were 156 probes with significantly increased methylation in placebo-treated cases versus normal tissues that were not significant between genistein-treated cases and normal tissues, suggesting that genistein may have had some demethylation effects. These 156 probes corresponded to at least 92 separate genes including ADCY4, ALOX12, HAAO, LRRC4, NEU1, RAPGEFL1, and WNT7B.These findings highlight the effects of genistein on global changes in DNA methylation in prostate cancer and its effects on molecular pathways involved in prostate tumorigenesis. We analyzed prostate tissue samples from a clinical trial, which was a randomized, placebo-controlled, double-blind Phase 2 study on Norwegian patients with localized prostate cancer who received 30 mg synthetic genistein or placebo capsules daily for 3-6 weeks before radical prostatectomy. We investigated the DNA methylation levels of prostate tumor samples from 10 patients who received genistein and 10 patients who received placebo. Four adjacent normal prostate tissue samples were also analyzed.