Abstract 4604: DNA methylation at chromosome 8q24 in peripheral blood and prostate cancer risk
Authors: Barry Kathryn Hughes , Moore Lee E. , Sampson Joshua , Koutros Stella , Yan Liying , Meyer Ann , Reddy Mahitha , Cook Michael B. , Fraumeni Joseph F. , Yeager Meredith , Amundadottir Laufey , Berndt Sonja I. 
Published: August 2015

Chromosome 8q24 has emerged as an important region for the genetic susceptibility to several cancers, including prostate cancer; however, little is known about the contribution of DNA methylation in this region to risk. To evaluate DNA methylation levels at 8q24 in relation to the risk of prostate cancer, we conducted a nested case-control study using pre-diagnostic peripheral blood samples from 694 prostate cancer cases and 703 controls in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We quantified DNA methylation levels at 63 specific CpG sites nearby cancer susceptibility single nucleotide polymorphisms (SNPs) at 8q24 or the MYC oncogene using pyrosequencing with bisulfite-treated DNA. For each of the 50 CpG sites meeting our quality control requirements, we used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the risk of prostate cancer associated with each unit increase in percent DNA methylation. We identified 7 CpG sites whose DNA methylation levels were associated with prostate cancer risk (p less than 0.05), including 5 CpG sites in POU5F1B that were moderately correlated with one another (Spearman rho: 0.20-0.52), as well as 2 intergenic CpG sites (Chr8:128081593 and Chr8:128513944). The most significant association was observed for Chr8:128498079 in POU5F1B (OR = 0.97, 95% CI: 0.95-0.99, p-value = 0.01). The five POU5F1B CpG sites found to be associated with prostate cancer risk were significantly correlated with several established cancer susceptibility SNPs at 8q24 from genome-wide association studies, including rs6983267 (rho: 0.14-0.36), which has been previously associated with prostate cancer, among other cancers. Rs6983267 was only marginally associated with prostate cancer risk in this study (p = 0.10). When rs6983267 was included in the models for the five correlated CpG sites at POU5F1B, the associations for these CpG sites with prostate cancer were attenuated, suggesting that the POU5F1B CpG sites may be part of the same biological pathway conferring increased prostate cancer risk. Our findings suggest that DNA methylation at 8q24 may contribute to the risk of prostate cancer, and epigenetic mechanisms may help explain some of the SNP-associated risk in this important cancer susceptibility region.

Citation Format: Kathryn Hughes Barry, Lee E. Moore, Joshua Sampson, Stella Koutros, Liying Yan, Ann Meyer, Mahitha Reddy, Michael B. Cook, Joseph F. Fraumeni, Meredith Yeager, Laufey Amundadottir, Sonja I. Berndt. DNA methylation at chromosome 8q24 in peripheral blood and prostate cancer risk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4604. doi:10.1158/1538-7445.AM2015-4604