eCite Digital Repository

Genome-wide measures of peripheral blood DNA methylation and prostate cancer risk in a prospective nested case-control study

Citation

FitzGerald, LM and Naeem, H and Makalic, E and Schmidt, DF and Dowty, JG and Joo, JE and Jung, C-H and Bassett, JK and Dugue, P-A and Chung, J and Lonie, A and Milne, RL and Wong, EM and Hopper, JL and English, DR and Severi, G and Baglietto, L and Pedersen, J and Giles, GG and Southey, MC, Genome-wide measures of peripheral blood DNA methylation and prostate cancer risk in a prospective nested case-control study, The Prostate, 77, (5) pp. 471-478. ISSN 0270-4137 (2017) [Refereed Article]

Copyright Statement

Copyright 2017 Wiley Periodicals

DOI: doi:10.1002/pros.23289

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.

Item Details

Item Type:Refereed Article
Keywords:prostate cancer, DNA methylation, peripheral blood, biomarker, HM450K array
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Genetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:FitzGerald, LM (Dr Liesel Fitzgerald)
ID Code:114207
Year Published:2017
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-02-08
Last Modified:2017-11-22
Downloads:0

Repository Staff Only: item control page