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

FitzGerald, LM ORCID: 0000-0002-6882-2698, Naeem, H, Makalic, E, Schmidt, DF, Dowty, JG, Joo, JE, Jung, C-H, Bassett, JK, Dugue, P-A, Chung, J, Lonie, A, Milne, RL, Wong, EM, Hopper, JL, English, DR, Severi, G, Baglietto, L, Pedersen, J, Giles, GG and Southey, MC 2017 , 'Genome-wide measures of peripheral blood DNA methylation and prostate cancer risk in a prospective nested case-control study' , The Prostate, vol. 77, no. 5 , pp. 471-478 , doi: 10.1002/pros.23289.

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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 Type: Article
Authors/Creators: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
Keywords: prostate cancer, DNA methylation, peripheral blood, biomarker, HM450K array
Journal or Publication Title: The Prostate
Publisher: Wiley-Liss
ISSN: 0270-4137
DOI / ID Number: 10.1002/pros.23289
Copyright Information:

Copyright 2017 Wiley Periodicals

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