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

BMC Medical Genomics

Ellen L Goode³  Julie M Cunningham⁴  Janet E Olson³  Viji Shridhar⁴  David N Rider³  Devin C Koestler²  Kimberly R Kalli⁵  Stacey J Winham³  Chen Wang³  Melissa C Larson³  Mine S Cicek³  Sebastian M Armasu³  Brooke L Fridley¹ 

[1] Department of Biostatistics, University of Kansas, Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA;Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth College, Lebanon, NH 03756, USA;Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA;Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA;Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

关键词: Overall survival;    Etiology;    Pathway;    Epithelial ovarian cancer;    CpG genotyping arrays;    DNA methylation;   

Others  :  797051
DOI  :  10.1186/1755-8794-7-21

 received in 2013-12-13, accepted in 2014-04-16,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Fridley et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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