Methylation of leukocyte DNA and ovarian cancer: relationships with disease status and outcome Journal Article

Authors: Fridley, Brooke L; Armasu, Sebastian M; Cicek, Mine S; Larson, Melissa C; Wang, Chen; Winham, Stacey J; Kalli, Kimberly R; Koestler, Devin C; Rider, David N; Shridhar, Viji; Olson, Janet E; Cunningham, Julie M; Goode, Ellen L
Article Title: Methylation of leukocyte DNA and ovarian cancer: relationships with disease status and outcome
Abstract: BACKGROUND: Genome-wide interrogation of DNA methylation (DNAm) in blood-derived leukocytes has become feasible with the advent of CpG genotyping arrays. In epithelial ovarian cancer (EOC), one report found substantial DNAm differences between cases and controls; however, many of these disease-associated CpGs were attributed to differences in white blood cell type distributions. METHODS: We examined blood-based DNAm in 336 EOC cases and 398 controls; we included only high-quality CpG loci that did not show evidence of association with white blood cell type distributions to evaluate association with case status and overall survival. RESULTS: Of 13,816 CpGs, no significant associations were observed with survival, although eight CpGs associated with survival at p < 10-3, including methylation within a CpG island located in the promoter region of GABRE (p = 5.38 x 10-5, HR = 0.95). In contrast, 53 CpG methylation sites were significantly associated with EOC risk (p <5 x10-6). The top association was observed for the methylation probe cg04834572 located approximately 315 kb upstream of DUSP13 (p = 1.6 x10-14). Other disease-associated CpGs included those near or within HHIP (cg14580567; p =5.6x10-11), HDAC3 (cg10414058; p = 6.3x10-12), and SCR (cg05498681; p = 4.8x10-7). CONCLUSIONS: We have identified several CpGs in leukocytes that are differentially methylated by case-control status. Since a retrospective study design was used, we cannot differentiate whether DNAm was etiologic or resulting from EOC; thus, prospective studies of EOC-associated loci are the critical next step.
Journal Title: BMC medical genomics
Volume: 7
Issue: 1
ISSN: 1755-8794
Publisher: Unknown  
Date Published: 2014