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Prostate. 2017 Apr;77(5):471-478. doi: 10.1002/pros.23289. Epub 2017 Jan 24.

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

Author information

1
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.
2
Cancer, Genetics, and Immunology, Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
3
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia.
4
Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC, Australia.
5
VLSCI Life Sciences Computation Centre, University of Melbourne, Carlton, VIC, Australia.
6
Université Paris-Saclay, University of Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.
7
Gustave Roussy, F-94805, Villejuif, France.
8
HuGeF, Human Genetics Foundation, Torino, Italy.
9
TissuPath, Mount Waverley, Melbourne, VIC, Australia.

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. © 2017 Wiley Periodicals, Inc.

KEYWORDS:

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

PMID:
28116812
DOI:
10.1002/pros.23289
[Indexed for MEDLINE]

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