• Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
• Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
• Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
• EpigenDx, Inc., Hopkinton, MA 01748, USA.
• Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
• Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
• Office of the Director, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
• Frederick National Laboratory for Cancer Research, Cancer Genomics Research Laboratory, Leidos Biomedical Research, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
• Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

BACKGROUND: Chromosome 8q24 has emerged as an important genetic susceptibility region for several cancers, including prostate cancer; however, little is known about the contribution of DNA methylation in this region to risk.

METHODS: We prospectively evaluated DNA methylation at 8q24 in relation to prostate cancer using pre-diagnostic blood samples from 694 prostate cancer cases (including 172 aggressive cases) and 703 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used logistic regression to estimate odds ratios and 95% confidence intervals.

RESULTS: Although none remained significant after adjustment for multiple testing (q>0.05), of the 50 CpG sites meeting quality control, we identified 8 sites that were nominally associated with prostate cancer (P_trend<0.05), including 6 correlated (Spearman ρ: 0.20-0.52) sites in POU5F1B and 2 intergenic sites (most significant site: Chr8:128428897 in POU5F1B, P_trend=0.01). We also identified two correlated (ρ=0.39) sites in MYC (Chr8:128753187 and Chr8:128753154) that were associated with aggressive (P_trend=0.02 and 0.03), but not non-aggressive disease (P_trend=0.70 and 0.20; P_{heterogeneity}=0.01 and 4.6 × 10^-3). These findings persisted after adjustment for the top 8q24 prostate cancer variants in our study.

CONCLUSIONS: Although requiring replication, our findings provide some evidence that 8q24 DNA methylation levels may be associated with prostate cancer risk.