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Genome‐Wide Measures of Peripheral Blood Dna Methylation and Prostate Cancer Risk in a Prospective Nested Case‐Control Study
Author(s) -
FitzGerald Liesel M.,
Naeem Haroon,
Makalic Enes,
Schmidt Daniel F.,
Dowty James G.,
Joo Jihoon E.,
Jung CholHee,
Bassett Julie K.,
Dugue PierreAntoine,
Chung Jessica,
Lonie Andrew,
Milne Roger L.,
Wong Ee Ming,
Hopper John L.,
English Dallas R.,
Severi Gianluca,
Baglietto Laura,
Pedersen John,
Giles Graham G.,
Southey Melissa C.
Publication year - 2017
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23289
Subject(s) - nested case control study , dna methylation , prostate cancer , medicine , peripheral blood , oncology , prospective cohort study , prostate , case control study , cancer , gynecology , genetics , biology , gene , gene expression
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 . © 2017 Wiley Periodicals, Inc.