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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 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 2017 Wiley Periodicals
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:||Refereed Article|
|Keywords:||prostate cancer, DNA methylation, peripheral blood, biomarker, HM450K array|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Oncology and carcinogenesis|
|Research Field:||Cancer genetics|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||FitzGerald, LM (Dr Liesel FitzGerald)|
|Web of Science® Times Cited:||25|
|Deposited By:||Menzies Institute for Medical Research|
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