Genome-Wide Measures of Peripheral Blood Dna Methylation and Prostate Cancer Risk in a Prospective Nested Case-Control Study

Liesel M. Fitzgerald, Haroon Naeem, Enes Makalic, Daniel F. Schmidt, James G Dowty, Jihoon E. Joo, Chol-Hee Jung, Julie K Bassett, Pierre Antoine Dugue, Jessica Chung, Andrew Lonie, Roger L Milne, Ee Ming Wong, John L. Hopper, Dallas R. English, Gianluca Severi, Laura Baglietto, John Pedersen, Graham G. Giles, Melissa C. Southey

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20 Citations (Scopus)

Abstract

BACKGROUND: Global measures of peripheral blood DNA methylation have been associated with risk of some malignancies, including breast, bladder, and gastric cancer. Here, we examined genome-wide measures of peripheral blood DNA methylation in prostate cancer and its non-aggressive and aggressive disease forms. METHODS: We used a matched, case-control study of 687 incident prostate cancer samples, nested within a larger prospective cohort study. DNA methylation was measured in pre-diagnostic, peripheral blood samples using the Illumina Infinium HM450K BeadChip. Genome-wide measures of DNA methylation were computed as the median M-value of all CpG sites and according to CpG site location and regulatory function. We used conditional logistic regression to test for associations between genome-wide measures of DNA methylation and risk of prostate cancer and its subtypes, and by time between blood draw and diagnosis. RESULTS: We observed no associations between the genome-wide measure of DNA methylation based on all CpG sites and risk of prostate cancer or aggressive disease. Risk of non-aggressive disease was associated with higher methylation of CpG islands (OR = 0.80; 95%CI = 0.68–0.94), promoter regions (OR = 0.79; 95%CI = 0.66–0.93), and high density CpG regions (OR = 0.80; 95%CI = 0.68–0.94). Additionally, higher methylation of all CpGs (OR = 0.66; 95%CI = 0.48–0.89), CpG shores (OR = 0.62; 95%CI = 0.45–0.84), and regulatory regions (OR = 0.68; 95% CI = 0.51–0.91) was associated with a reduced risk of overall prostate cancer within 5 years of blood draw but not thereafter. CONCLUSIONS: A reduced risk of overall prostate cancer within 5 years of blood draw and non-aggressive prostate cancer was associated with higher genome-wide methylation of peripheral blood DNA. While these data have no immediate clinical utility, with further work they may provide insight into the early events of prostate carcinogenesis. Prostate 77:471–478, 2017.

Original languageEnglish
Pages (from-to)471-478
Number of pages8
JournalThe Prostate
Volume77
Issue number5
DOIs
Publication statusPublished - 1 Apr 2017
Externally publishedYes

Keywords

  • biomarker
  • DNA methylation
  • HM450K array
  • peripheral blood
  • prostate cancer

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